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Diabetes mellitus

Introduction
Diabetes mellitus often simply referred to as diabetesis a condition in which a person has a high blood sugar (glucose) level as a result of the body either not producing enough insulin, or because body cells do not properly respond to the insulin that is produced. Insulin is a hormone produced in the pancreas which enables body cells to absorb glucose, to turn into energy. If the body cells do not absorb the glucose, the glucose accumulates in the blood (hyperglycemia), leading to various potential medical complications. There are many types of diabetes, the most common of which are:

Type 1 diabetes: results from the body's failure to produce insulin, and presently requires the person to inject insulin. Type 2 diabetes: results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. Gestational diabetes: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM.

Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes. All forms of diabetes have been treatable since insulin became medically available in 1921, and type 2 diabetes can be controlled with tablets, but it is chronic condition that usually cannot be cured. Pancreas transplants have been tried with limited success in type 1 DM; gastric bypass surgery has been successful in many with morbid obesity and type 2 DM; and gestational diabetes usually resolves after delivery. Diabetes without proper treatments can cause many complications. Acute complications include hypoglycemia, diabetic ketoacidosis, or nonketotic hyperosmolar coma. Serious long-term complications include cardiovascular disease, chronic renal failure, retinal damage. Adequate treatment of diabetes is thus important, as well as blood pressure control and lifestyle factors such as smoking cesation and maintaining a healthy body weight. As of 2000 at least 171 million people worldwide suffer from diabetes, or 2.8% of the population. Type 2 diabetes is by far the most common, affecting 90 to 95% of the U.S. diabetes population.

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Diabetes mellitus

Classification
Most cases of diabetes mellitus fall into the three broad categories of type 1 or type 2 and gestational diabetes. A few other types are described. The term diabetes, without qualification, usually refers to diabetes mellitus, which roughly translates to excessive sweet urine (known as "glycosuria"). Several rare conditions are also named diabetes. The most common of these is diabetes insipidus in which large amounts of urine are produced (polyuria), which is not sweet (insipidus meaning "without taste" in Latin). The term "type 1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesityrelated diabetes, and non-insulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature. Various sources have defined "type 3 diabetes" as: gestational diabetes, insulin-resistant type 1 diabetes (or "double diabetes"), type 2 diabetes which has progressed to require injected insulin, and latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes)

Type 1 diabetes
Diabetes mellitus type 1 Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas leading to insulin deficiency. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, where beta cell loss is a T-cell mediated autoimmune attack. There is no known preventive measure against type 1 diabetes, which causes approximately 10% of diabetes mellitu cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults but was traditionally termed "juvenile diabetes" because it represents a majority of the diabetes cases in children.

Type 2 diabetes
Diabetes mellitus type 2 Type 2 diabetes mellitus is characterized by insulin resistance which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus due to a known defect are classified separately. Type 2 diabetes is the most common type. In the early stage of type 2 diabetes, the predominant abnormality is reduced insulin sensitivity. At this stage hyperglycemia can be reversed by a variety of measures and medications that
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improve insulin sensitivity or reduce glucose production by the liver. As the disease progresses, the impairment of insulin secretion occurs, and therapeutic replacement of insulin may sometimes become necessary in certain patients.

Gestational diabetes
Gestational diabetes Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20% 50% of affected women develop type 2 diabetes later in life. Even though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A cesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia. A 2008 study completed in the U.S. found that more American women are entering pregnancy with preexisting diabetes. In fact the rate of diabetes in expectant mothers has more than doubled in the past 6 years. This is particularly problematic as diabetes raises the risk of complications during pregnancy, as well as increasing the potential that the children of diabetic mothers will also become diabetic in the future.

Other types
Pre-diabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 diabetes. Many people destined to develop type 2 diabetes spend many years in a state of pre-diabetes which has been termed "America's largest healthcare epidemic. Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulinantagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or
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MMDM, ICD-10 code E12), was deprecated by the World Health Organization when the current taxonomy was introduced in 1999.

Signs and symptoms


Overview of the most significant symptoms of diabetes. The classical symptoms of DM are: polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children. However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause a rapid yet significant weight loss (despite normal or even increased eating) and irreducible mental fatigue. All of these symptoms except weight loss can also manifest in type 2 diabetes in patients whose diabetes is poorly controlled, although unexplained weight loss may be experienced at the onset of the disease. Final diagnosis is made by measuring the blood glucose concentration. When the glucose concentration in the blood is raised beyond its renal threshold (about 10 mmol/L, although this may be altered in certain conditions, such as pregnancy), reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst. Prolonged high blood glucose causes glucose absorption, which leads to changes in the shape of the lenses of the eyes, resulting in vision changes; sustained sensible glucose control usually returns the lens to its original shape. Blurred vision is a common complaint leading to a diabetes diagnosis; type 1 should always be suspected in cases of rapid vision change, whereas with type 2 change is generally more gradual, but should still be suspected. Patients (usually with type 1 diabetes) may also initially present with diabetic ketoacidosis (DKA), an extreme state of metabolic dysregulation characterized by the smell of acetone on the patient's breath; a rapid, deep breathing known as Kussmaul breathing; polyuria; nausea; vomiting and abdominal pain; and any of many altered states of consciousness or arousal (such as hostility and mania or, equally, confusion and lethargy). In severe DKA, coma may follow, progressing to death. Diabetic ketoacidosis is a medical emergency and requires immediate hospitalization.

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Diabetes mellitus

A rarer but equally severe possibility is hyperosmolar nonketotic state, which is more common in type 2 diabetes and is mainly the result of dehydration due to loss of body water. Often, the patient has been drinking extreme amounts of sugar-containing drinks, leading to a vicious circle in regard to the water loss. A number of skin rashes can occur in diabetes that are collectively known as diabetic dermadromes.

Causes

Type 2 diabetes is determined primarily by lifestyle factors and genes.

Lifestyle
A number of lifestyle factors are known to be important to the development of type 2 diabetes. In one study, those who had high levels of physical activity, a healthy diet, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight was included the rate was 89% lower. In this study a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index.Obesity has been found to contribute to approximately 55% type 2 diabetes, and decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk The increased rate of childhood obesity in between the 1960s and 2000s is believed to have lead to the increase in type 2 diabetes in children and adolescents. Environmental toxins may contribute to recent increases in the rate of type 2 diabetes. A positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of some plastics, and the incidence of type 2 diabetes.

Medical conditions
Subclinical Cushing's syndrome (cortisol excess) may be associated with DM type 2. The percentage of subclinical Cushing's syndrome in the diabetic population is about 9%.Diabetic patients with a pituitary microadenoma can improve insulin sensitivity by removal of these microadenomas. Hypogonadism is often associated with cortisol excess, and testosterone deficiency is also associated with diabetes mellitus type 2, even if the exact mechanism by which testosterone improve insulin sensitivity is still not known.

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Diabetes mellitus

Genetics

Both type 1 and type 2 diabetes are partly inherited. Type 1 diabetes may be triggered by certain infections, with some evidence pointing at Coxsackie B4 virus. There is a genetic element in individual susceptibility to some of these triggers which has been traced to particular HLA genotypes (i.e., the genetic "self" identifiers relied upon by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger. There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 have a much higher risk of developing type 2, increasing with the number of those relatives. Concordance among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX. KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7like 2) regulates proglucagon gene expression and thus the production of glucagon-like peptide-1. Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited. Monogenic forms, e.g., MODY, constitute 15 % of all cases. Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich's ataxia. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD. Gene expression promoted by a diet of fat and glucose as well as high levels of inflammation related cytokines found in the obese results in cells that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance.

Pathophysiology
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Diabetes mellitus

The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals. One of the effects of a sugar-rich vs a starch-rich meal is highlighted. Mechanism of insulin release in normal pancreatic beta cells. Insulin production is more or less constant within the beta cells, irrespective of blood glucose levels. It is stored within vacuoles pending release, via exocytosis, which is primarily triggered by food, chiefly food containing absorbable glucose. The chief trigger is a rise in blood glucose levels after eating Insulin is the principal hormone that regulates uptake of glucose from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus. Humans are capable of digesting some carbohydrates, in particular those most common in food; starch, and some disaccharides such as sucrose, are converted within a few hours to simpler forms most notably the monosaccharide glucose, the principal carbohydrate energy source used by the body. The most significant exceptions are fructose, most disaccharides (except sucrose and in some people lactose), and all more complex polysaccharides, with the outstanding exception of starch. The rest are passed on for processing by gut flora largely in the colon. Insulin is released into the blood by beta cells (-cells), found in the Islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Insulin is also the principal control signal for conversion of glucose to glycogen for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone glucagon which acts in the opposite manner to insulin. Glucose thus forcibly produced from internal liver cell stores (as glycogen) re-enters the bloodstream; muscle cells lack the necessary export mechanism. Normally liver cells do this when the level of insulin is low (which normally correlates with low levels of blood glucose). Higher insulin levels increase some anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat burning metabolic phase).
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If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, then glucose will not have its usual effect so that glucose will not be absorbed properly by those body cells that require it nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.

Diagnosis

Glycosylated hemoglobin and Glucose tolerance test

1999 WHO Diabetes criteria Condition 2 hour glucose Fasting glucose mmol/l(mg/dl) mmol/l(mg/dl) Normal Impaired fasting glycaemia Impaired glucose tolerance Diabetes mellitus <7.8 (<140) <7.8 (<140) 7.8 (140) 11.1 (200) <6.1 (<110) 6.1(110) & <7.0(<126) <7.0 (<126) 7.0 (126)

Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:
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Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dL). Plasma glucose at or above 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test. Symptoms of hyperglycemia and casual plasma glucose at or above 11.1 mmol/L (200 mg/dL). Glycated hemoglobin (hemoglobin A1C) at or above 6.5. (This criterion was recommended by the American Diabetes Association in 2010; it has yet to be adopted by the WHO.)

About a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis (a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids) by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening; detection of hyperglycemia during other medical investigations; and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that is frequently caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia. A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus. Patients with fasting glucose levels from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus as well as cardiovascular disease.

Screening
Diabetes screening is recommended for many people at various stages of life, and for those with any of several risk factors. The screening test varies according to circumstances and local policy, and may be a random blood glucose test, a fasting blood glucose test, a blood glucose test two hours after 75 g of glucose, or an even more formal glucose tolerance test. Many healthcare providers recommend universal screening for adults at age 40 or 50, and often periodically thereafter. Earlier screening is typically recommended for those with risk factors such as obesity, family history of diabetes, high-risk ethnicity (Hispanic, Native American, Afro-Caribbean, Pacific Islander, or Mori). Many medical conditions are associated with diabetes and warrant screening. A partial list includes: subclinical Cushing's syndrome, testosterone deficiency, high blood pressure, elevated cholesterol levels, coronary artery disease, past gestational diabetes, polycystic ovary syndrome, chronic pancreatitis, fatty liver, hemochromatosis, cystic fibrosis,
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several mitochondrial neuropathies and myopathies (such as MIDD), myotonic dystrophy, Friedreich's ataxia, some of the inherited forms of neonatal hyperinsulinism. The risk of diabetes is higher with chronic use of several medications, including long term corticosteroids, some chemotherapy agents (especially L-asparaginase), as well as some of the antipsychotics and mood stabilizers (especially phenothiazines and some atypical antipsychotics). People with a confirmed diagnosis of diabetes are tested routinely for complications. This includes yearly urine testing for microalbuminuria and examination of the retina of the eye for retinopathy.

Accuracy of tests for early detection


If a 2-hour postload glucose level of at least 11.1 mmol/L ( 200 mg/dL) is used as the reference standard, the fasting plasma glucose > 7.0 mmol/L (126 mg/dL) diagnoses current diabetes with:

sensitivity about 50% specificity greater than 95%

A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses current diabetes with

sensitivity = 75% specificity = 88%

Glycosylated hemoglobin values that are elevated (over 5%), but not in the diabetic range (not over 7.0%) are predictive of subsequent clinical diabetes in US female health professionals. In this study, 177 of 1061 patients with glycosylated hemoglobin value less than 6% became diabetic within 5 years compared to 282 of 26281 patients with a glycosylated hemoglobin value of 6.0% or more. This equates to a glycosylated hemoglobin value of 6.0% or more having:

sensitivity = 16.7% specificity = 98.9%

Benefit of early detection


Since publication of the USPSTF statement, a randomized controlled trial of prescribing acarbose to patients with "high-risk population of men and women between the ages of 40 and 70 years with a body mass index (BMI), calculated as weight in kilograms divided by the square of height in meters, between 25 and 40. They were eligible for the study if they had IGT according to the World Health Organization criteria, plus impaired fasting glucose (a fasting plasma glucose concentration of between 100 and 140 mg/dL or 5.5 and 7.8 mmol/L) found a number needed to treat of 44 (over 3.3 years) to prevent a major cardiovascular event. Other studies have shown that lifestyle changes, xenical and metformin can delay the onset of diabetes.

Management
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Main article: Diabetes management Left untreated, diabetes mellitus type 2 is a chronic, progressive condition, but there are wellestablished treatments which can delay or prevent entirely the formerly inevitable consequences of the condition. Often, the condition is viewed as progressive since poor management of blood sugar leads to a myriad of steadily worsening complications. However, if blood sugar is properly maintained, then the condition is, in a limited sense, cured - that is, patients are at no heightened risk for neuropathy, blindness, or any other high blood sugar complication, though the underlying isssue, a tendency to hyperglycemia has not been addressed directly. A study at UCLA in 2005 showed that the Pritikin Program of diet and exercise brought dramatic improvement to a group of diabetics and pre-diabetics in only three weeks, so that about half no longer met the criteria for the condition. There are two main goals of treatment: 1. reduction of mortality and concomitant morbidity (from assorted diabetic complications) 2. preservation of quality of life The first goal can be achieved through close glycemic control (i.e., to near 'normal' blood glucose levels); the reduction in severity of diabetic side effects has been very well demonstrated in several large clinical trials and is established beyond controversy. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (usually physician, PA, nurse, dietitian or a certified diabetic educator). Endocrinologists, family practitioners, and general internists are the physician specialties most likely to treat people with diabetes. Knowledgeable patient participation is vital to clinical success, and so patient education is a crucial aspect of this effort. Type 2 is initially treated by adjustments in diet and exercise, and by weight loss, most especially in obese patients. The amount of weight loss which improves the clinical picture is sometimes modest (25 kg or 4.4-11 lb); this is almost certainly due to currently poorly understood aspects of fat tissue activity, for instance chemical signaling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity. In some cases strict diet can adequately control the glycemic levels. Diabetes education is an integral component of medical care. Among adults with diagnosed diabetes, 12% take both insulin and oral medications,19% take insulin only, 53% take oral medications only, and 15% do not take either insulin or oral medications.

Goals
Treatment goals for type 2 diabetic patients are related to effective control of blood glucose, blood pressure and lipids to minimize the risk of long-term consequences associated with diabetes. They are suggested in clinical practice guidelines released by various national and international diabetes agencies.
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The targets are:


HbA1c of 6% to 7.0% Preprandial blood glucose: 4.0 to 6.0 mmol/L (72 to 108 mg/dl) 2-hour postprandial blood glucose: 5.0 to 8.0 mmol/L (90 to 144 mg/dl)

In older patients, clinical practice guidelines by the American Geriatrics Society states "for frail older adults, persons with life expectancy of less than 5 years, and others in whom the risks of intensive glycemic control appear to outweigh the benefits, a less stringent target such as HbA1c of 8% is appropriate"

Prevention
Type 1
Type 1 diabetes risk is known to depend upon a genetic predisposition based on HLA types (particularly types DRs3 and DR4), an unknown environmental trigger (suspected to be an infection, although none has proven definitive in all cases), and an uncontrolled autoimmune response that attacks the insulin producing beta cells. Some research has suggested that breastfeeding decreased the risk in later life; various other nutritional risk factors are being studied, but no firm evidence has been found. Giving children 2000 IU of Vitamin D during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure. Children with antibodies to beta cell proteins (i.e. at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B-3 (niacin), had less than half the diabetes onset incidence in a 7-year time span as did the general population, and an even lower incidence relative to those with antibodies as above, but who received no vitamin B3.

Type 2
Lifestyle Type 2 diabetes risk can be reduced in many cases by making changes in diet and increasing physical activity. The American Diabetes Association (ADA) recommends maintaining a healthy weight, getting at least 2 hours of exercise per week (several brisk sustained walks appear sufficient), having a modest fat intake, and eating sufficient fiber (e.g., from whole grains). The ADA does not recommend alcohol consumption as a preventive, but it is interesting to note that moderate alcohol intake may reduce the risk (though heavy consumption absolutely and clearly increases damage to bodily systems significantly); a similarly confused connection between low dose alcohol consumption and heart disease is termed the French Paradox. There is inadequate evidence that eating foods of low glycemic index is clinically helpful despite recommendations and suggested diets emphasizing this approach.

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Diets that are very low in saturated fats reduce the risk of becoming insulin resistant and diabetic. Study group participants whose "physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes." In another study of dietary practice and incidence of diabetes, "foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized." There are numerous studies which suggest connections between some aspects of Type II diabetes with ingestion of certain foods or with some drugs. Breastfeeding may also be associated with the prevention of type 2 of the disease in mothers.

Medications
Some studies have shown delayed progression to diabetes in predisposed patients through prophylactic use of metformin, rosiglitazone, or valsartan. In patients on hydroxychloroquine for rheumatoid arthritis, incidence of diabetes was reduced by 77% though causal mechanisms are unclear. Lifestyle interventions are however more effective than metformin at preventing diabetes regardless of weightloss.
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Management
Diabetes management Diabetes mellitus is a chronic disease which is difficult to cure. Management concentrates on keeping blood sugar levels as close to normal ("euglycemia") as possible without presenting undue patient danger. This can usually be with close dietary management, exercise, and use of appropriate medications (insulin only in the case of type 1 diabetes mellitus. Oral medications may be used in the case of type 2 diabetes, as well as insulin).

Lifestyle modifications
Diabetic diet
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There are roles for patient education, dietetic support, sensible exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure in patients with hypertension, cholesterol in those with dyslipidmia, as well as exercising more, smoking less or ideally not at all, consuming a recommended diet. Patients with foot problems are also recommended to wear diabetic socks , and possibly diabetic shoes

Medications
Oral medications : Anti-diabetic drug Insulin Insulin therapy Type 1 treatments usually include combinations of regular or NPH insulin, and/or synthetic insulin analogs.

Support
In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care of a patient in a team approach. Optometrists, podiatrists/chiropodists, dietitians, physiotherapists, nursing specialists (e.g., DSNs (Diabetic Specialist Nurse)), nurse practitioners, or Certified Diabetes Educators, may jointly provide multidisciplinary expertise. In countries where patients must provide for their own health care (e.g. in the US, and in much of the undeveloped world). Peer support links people living with diabetes. Within peer support, people with a common illness share knowledge and experience that others, including many health workers, do not have. Peer support is frequent, ongoing, accessible and flexible and can take many formsphone calls, text messaging, group meetings, home visits, and even grocery shopping. It complements and enhances other health care services by creating the emotional, social and practical assistance necessary for managing disease and staying healthy.

Diabetes mellitus type 2


Diabetes mellitus type 2 or type 2 diabetes (formerly called non -insulin-dependent diabetes mellitus (NIDDM), or adult-onset diabetes) is a disorder that is characterized by high blood
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glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and dietary modification. As the condition progresses, medications are typically needed. There are an estimated 23.6 million people in the U.S. (7.8% of the population) with diabetes with 17.9 million being diagnosed, 90% of whom are type 2. With prevalence rates doubling between 1990 and 2005, CDC has characterized the increase as an epidemic. Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates due to alterations in dietary patterns as well as in life styles during childhood. Unlike type 1 diabetes, there is very little tendency toward ketoacidosis in type 2 diabetes, though it is not unknown. One effect that can occur is nonketonic hyperglycemia which also is quite dangerous, though it must be treated very differently. Complex and multifactorial metabolic changes very often lead to damage and function impairment of many organs, most importantly the cardiovascular system in both types. This leads to substantially increased morbidity and mortality in people with both type 1 and type 2 diabetes, but the two have quite different origins and treatments despite the similarity in complications.

Diabetes Nutrition
Are you tired of taking insulin pills and injections for maintaining your blood sugar levels? Have you ever thought about the health advantages that can be derived from the consumption of food supplements? If not, think about it! The transition to the diabetic lifestyle will be much easier. Diabetes is one of the most prevalent chronic diseases in the world. It prevents the body from using glucose in our food for taking care of its energy needs. This glucose gets accumulated in our blood, thereby risking the well-being of our heart, eyes, kidneys and nerves.

Nutritional Supplements for Diabetics


Recent researches carried out by food industries and health experts conclude that herbal supplements such as bitter melon, goats rue, nopal cactus, fenugreek, bilberry, gurmar, onions and garlic are quite effective in lowering the blood glucose level, thereby helping the patients to undergo less treatment distress. Diabetics must be always cautious about the source of their calorie intake. Non starchy veggies, skimmed milk, lean chicken, high fiber fruits and low glycemic food products are smart choices for an informed diabetic. Oil low in saturated fats content should be preferred. It had been proved that a balanced diabetic diet contains some important
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nutrients and useful supplements to help control dancing blood sugar. Lets see few useful diabetic nutritional supplements we receive from our food, and their action in controlling diabetes.

Biotin It helps the body in metabolizing carbohydrates, proteins and fats. Vitamin C It prevents sugar from getting attached to proteins. Insulin deficiency hinders effective metabolism and transport of Vitamin C, making its increased intake all the more important. Here, ascorbates like EmergenC is more preferred as compared to ascorbic acid. Chromium It aids the metabolism of glucose. It is most effective if consumed as niacin. Vitamin E It helps in improving insulin sensitivity. Magnesium It helps in lowering blood pressure and reducing heart-attack risks by relaxing the muscle tissues. CLA It helps in protecting cells from becoming diabetic or getting damaged by atherosclerosis, colon cancer and chronic inflammation. Omega 3 and Alpha Lipoic Acids - They are effective building blocks and antioxidants respectively. They reduce the risks associated with nerve damages by aiding balancing of blood sugar. Vitamin B6 It helps in preventing neuropathy. Vitamin D It helps in reducing insulin resistance and averting the risks of cataract. Zinc It helps in improving the action of insulin.

Diabetics have greater needs of nutritional supplements for fulfilling the antioxidant and metabolic requirements of the body. Design your food intake as per the above necessities and living the diabetic lifestyle will be a much easier road to travel upon.

Vitamin B1 Niacinamide Vitamin B12 Deficiency Vitamin E L-Carnitine Taurine Zinc Nutritional Brewers Yeast Glucomannan Benefits Primrose Oil Benefits

Biotin Vitamin B6 Vitamin D Coenzyme Q10 Inositol Manganese Alpha Lipoic Acid Diabetes and Chromium Supplements Magnesium Supplementation Dietary Fiber Food

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When diet, exercise and ideal body weight arent enough to maintain normal blood sugar level, you may need to start medication. Medications used to treat diabetes include insulin too. Usually, people with Type 1 diabetes don't use oral medications. Diabetes Medications work best in people with Type 2 diabetes who are having high blood sugar for less than ten years with normal weight or obesity. Some people who begin treatment with oral medications eventually need to take insulin. Unfortunately, insulin cannot be taken in pills form because enzymes in your stomach alter it, which makes it ineffective. Hence, insulin is taken with insulin syringe or insulin pump. Insulin and oral diabetes medications deliberately work to lower your blood sugar. In certain cases medications taken for other conditions may affect glucose levels. Blood sugar levels may rise due to corticosteroids. Thiazides medications are used to control high blood pressure and niacin is used to lower high cholesterol. Your doctor has to change your diabetes treatment, if you need to take certain high blood pressure medications. Number of drug options exists in market for treating type 2 diabetes, including: When diet, exercise and ideal body weight arent enough to maintain normal blood sugar level, you may need to start medication. Medications used to treat diabetes include insulin too. Usually, people with Type 1 diabetes don't use oral medications. Diabetes Medications work best in people with Type 2 diabetes who are having high blood sugar for less than ten years with normal weight or obesity. Some people who begin treatment with oral medications eventually need to take insulin. Unfortunately, insulin cannot be taken in pills form because enzymes in your stomach alter it, which makes it ineffective. Hence, insulin is taken with insulin syringe or insulin pump. Insulin and oral diabetes medications deliberately work to lower your blood sugar. In certain cases medications taken for other conditions may affect glucose levels. Blood sugar levels may rise due to corticosteroids. Thiazides medications are used to control high blood pressure and niacin is used to lower high cholesterol. Your doctor has to change your diabetes treatment, if you need to take certain high blood pressure
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medications. Number of drug options exists in market for treating type 2 diabetes, including: When diet, exercise and ideal body weight arent enough to maintain normal blood sugar level, you may to start medication. Medications used to treat diabetes include insulin too. Usually, people with Type 1 diabetes don't use oral medications. Diabetes Medications work best in people with Type 2 diabetes who are having high blood sugar for less than ten years with normal weight or obesity. Some people who begin treatment with oral medications eventually need to take insulin. Unfortunately, insulin cannot be taken in pills form because enzymes in your stomach alter it, which makes it ineffective. Hence, insulin is taken with insulin syringe or insulin pump. Insulin and oral diabetes medications deliberately work to lower your blood sugar. In certain cases medications taken for other conditions may affect glucose levels. Blood sugar levels may rise due to corticosteroids. Thiazides medications are used to control high blood pressure and niacin is used to lower high cholesterol. Your doctor has to change your diabetes treatment, if you need to take certain high blood pressure medications. Number of drug options exists in market for treating type 2 diabetes, including:

Sulfonylureas

Since 1994, sulfonylureas is the only drug used for diabetes in United States. It stimulates the pancreas for the production of more insulin to lower down the blood sugar. It can be effective when the pancreas can release some insulin by its own. Sulfonylureas such as glipizide (Glucotrol, Glucotrol XL), glyburide (DiaBeta, Glynase PresTab, Micronase) and glimepiride (Amaryl) are prescribed more often. If your body is sensitive to sulfa drug then you must avoid sulfonylureas. Side Effects:

Low blood sugar. Stomach upset. Skin rash and itching. Weight gain.

Biguanides
Metformin (Glucophage, Glucophage XR) is the generic name of this drug. It works by inhibiting the production and release of glucose from your liver. It also lowers down the
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insulin secretion. One good thing about biguanides drug is that it tends to low down weight gain than do others. It can also improve blood cholesterol level, which is enerally high if you are type 2 diabetic.

Side Effects:

If you already have a kidney problem, metformin may build up in your body. Inform your doctor when you are placed on this medication regarding your kidney problem. If you are vomiting, have diarrhea, and can't drink enough fluids, you may need to stop taking this diabetes medication for a few days. You may feel metallic taste. If you are going for medical test using dye, or planning to opt for any surgery, then inform your doctor about your metformin intake. He will instruct you to stop taking metformin for some specific period.

Alpha-glucosidase Inhibitors

Alpha-glucosidase inhibitors are of two types, acarbose and miglitol. They block the enzymes of digestive system which are responsible for the break down of the starches you eat. The sugar produced is absorbed slowly and helps prevent the rise of blood sugar level throughout the day, but usually right after meals. Drugs under this class are Acarbose (Precose) and Miglitol (Glyset).

Side Effects:

Stomach problems such as gas, bloating and diarrhea etc.- temporary effects. High dosages may cause permanent changes in liver.

Clinical diagnosis of the diabetes require some of the laboratory tests, glycosuria (finding glucose in the urine) is one of the significant test for detecting frank diabetes. Those who are non diabetic, for them glycosuria can occur for the short term due to emotional stress, pain, hyperthyroidism, alimentary hyperglycemia or meningitis. It can also occur when there is insufficiency of insulin and if a substantial amount of food with high sugar is consumed.

Glycosuria is a condition in which glucose or simple sugar is detected in the urine despite of normal blood sugar level. The normally functioning kidneys absorb and reabsorb the extra blood sugar till renal threshold, with the help of millions of micro tubules Nephron (filtering unit of
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kidney). The renal threshold is a concentration level above which all simple sugar is not absorbed in the blood; hence extra glucose is excreted by the kidneys in the urine. Renal threshold of normal kidney is around 10mmol/L. In few cases, when drugs are used for a longer span of time, it may alter the threshold level of kidney. The amount of glucose not reabsorbed by the kidneys is usually less than 0.1%. Adults excrete about 65 mg of glucose per day. The relationship between glycosuria and the renal threshold are explained in the diagram given below. In renal glycosuria glucose is abnormally eliminated in the urine due to improper action of the nephron. The renal glycosuria occurs only when there are abnormally functioning kidneys, due some dent in the kidneys or as an autosomal recessive trait. The generic names for these drugs are pioglitazone (Actos) and Troglitazone (Rezulin), Rosiglitazone (Avandia). Troglitzeone (Rezulin) was banned in March 2000 as it causes liver failure. Thiazolidinediones drug makes your body tissue more sensitive to insulin. The insulin can then move glucose from your blood into your cells for the production of energy.

Side Effects:
It may affect your liver function and lead to nausea, vomiting, stomach pain, lack of appetite, tiredness, yellowing of the skin or whiteness in the eyes, or dark-colored urine. If you take birth control pills, this drug may decrease its effectiveness in preventing pregnancy. Unusual weight gain. Loss of appetite may develop risk of anemia which will make you feel tired. Swelling in the legs or ankles.

Meglitinides is available with the generic name Repaglinide (Prandin). It helps the pancreas to produce more insulin right after meals which lowers blood sugar. Its effect is much similar to short acting sulfonylureas. Meglitinides works quickly, and the results fade rapidly, so your doctor might prescribe Repaglinide only or with Metformin. Side Effects:

weight gain low blood sugar

Juvenile diabetes is an autoimmune disorder which can be due to environmental trigger or virus, which hampers the function of beta cell. Once the beta cells are destroyed the body is unable to produce insulin. It is also believed that Type 1 diabetes results from an infectious or toxic insult to a child, whose immune system is predisposed to develop an aggressive autoimmune response either against molecules
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of the B cell or against altered pancreatic B antigens, resembling a viral protein. A child with diabetic siblings is more prone to develop juvenile diabetes than the child from a totally unaffected family. It is considered to be a more hereditary problem than excess eating or being obese. Pancreas produces the exact amount of insulin, to breakdown the sugar produced in the body. The juvenile diabetic lack the production of insulin so, sugar builds up high in the blood, overflows into the urine and passes from the body unused. It is estimated that about 10-15% in United States are suffering with juvenile diabetes. Approximately 35 American children are diagnosed with juvenile diabetes every day.

To keep your blood glucose in control through out the day you need diet modifications, regular exercise, medicine (tablets/insulin injections). Insulin injection is not needed immediately after the diagnosis of diabetes is made (unless your doctor feels this is an emergency). If you are obese you need to reduce your weight through diet control and give up sedentary habits so that your insulin works better. Your treatment should be started and supervised by an expert, who should review every 3-6 months to help you keep your blood glucose in control. You should register in a diabetic clinic for regular blood pressure check ups, ECG and advice for care. Treatment is aimed at maintaining the blood glucose in the normal range and HbA1c less than 7%, by balancing food intake with oral medication or insulin and physical activity year after year, to prevent complications of diabetes. An emotional stress (a death in family, displeasure at work or at home) may increase and disturb the control of diabetes. You need to discuss the problem with your doctor for suitable adjustment in dosage of medication and stress control exercises. By keeping a good control of diabetes at all times, you will be able to prevent the complications of diabetes affecting the nerves, eyes, kidneys, heart and blood vessels.

Tips for diabetics before and during pregnancy


Coordinate with the health care team to achieve blood sugar level close to the normal range. Consult with a doctor, who has experience in handling diabetes mellitus during pregnancy. Put some extra care to the eyes and kidneys and check it frequently, because pregnancy may make it worst. Stop smoking, drinking alcohol, or use of harmful drugs.

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Consult and coordinate with an experienced dietician and plan your meal and follow it strictly and make sure the mother and the unborn baby have a healthy diet.

If already pregnant, then consult the doctor right away. Its not too late to bring the blood sugar close to normal so that the mother and the baby stay healthy during the rest of the pregnancy.

Diabetes pregnancy management

Diabetes mellitus may be effectively managed by appropriate meal planning, increased physical activity and properly-instituted insulin treatment. Some tips for controlling diabetes in pregnancy include:

Meals cut down sweets, eats three small meals and one to three snacks a day, maintain proper mealtimes, and include balanced fiber intake in the form of fruits, vegetables and whole-grains. Increased physical activity - walking, swimming/aquaerobics, etc. Monitor blood sugar level frequently, doctors may asked to check the blood glucose more often than usual. The blood sugar level should be below 95 mg/dl (5.3 mmol/l) on awakening, below 140 mg/dl (7.8 mmol/l) after one hour of meal and below 120 mg/dl (6.7 mmol/l) after two hours of a meal. Each time when checking the blood sugar level, keep a proper record of the results and present to the health care team for evaluation and modification of the treatment. If blood sugar levels are above targets, a perinatal diabetes management team may suggest ways to achieve targets. Many may need extra insulin during pregnancy to reach their blood sugar target. Insulin is not harmful for the baby.

Breast feeding
Breast feeding is good for the child even with a mother with diabetes mellitus. Some women wonder whether breast feeding is recommended after they have been diagnosed with diabetes mellitus. Breast feeding is recommended for most babies, including when mothers may be diabetic. In fact, the childs risk for developing type 2 diabetes mellitus later in life may be lower if the baby was breast-fed. It also helps the child to maintain a healthy body weight in infancy.

Classification
The White classification, named after Priscilla White who pioneered research on the effect of diabetes types on perinatal outcome, is widely used to assess maternal and fetal risk. It distinguishes between gestational diabetes (type A) and diabetes that existed before pregnancy

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(pregestational diabetes). These two groups are further subdivided according to their associated risks and management. There are 2 classes of gestational diabetes (diabetes which began during pregnancy):

Class A1: gestational diabetes; diet controlled Class A2: gestational diabetes; insulin controlled

The second group of diabetes which existed before pregnancy can be split up into these classes:

Class Class Class Class Class Class Class Class

B: onset at age 20 or older or with duration of less than 10 years C: onset at age 10-19 or duration of 1019 years D: onset before age 10 or duration greater than 20 years F: diabetic nephropathy R: proliferative retinopathy RF: retinopathy and nephropathy H: ischemic heart disease T: prior kidney transplant

An early age of onset or long-standing disease comes with greater risks, hence the first three subtypes.

Functions of Insulin
In addition to its role of regulating glucose metabolism, insulin also

Stimulates lipogenesis Diminishes lipolysis Increases amino acid transport into cells Modulates transcription Altering the cell content of numerous mRNAs Stimulates growth DNA synthesis Cell replication

Structure of Insulin Insulin resistance Insulin Regimens Diabetes and Insulin Analogs Diabetes Treatment and Insulin Problems

Insulin Synthesis Types of Insulin Diabetes Insulin Classification Insulin Injection Devices Insulin Syringes

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Insulin Pump Diabetes and Blood Sugar Levels

Inhaled Insulin

Insulin regimen is the way that your insulin injections are organized throughout the day. Type1 diabetics need more than one injection per day and use more than one type of insulin. The combination of insulins and the number of times you take your injections, frame your insulin regimen. There are numerous types of insulin regimens. Ideally, you will develop an individualized regimen that fits in with your life style. Two standard types of insulin regimen are discussed here. 1. Twice-daily mixture of short acting and intermediate or long acting insulin It is a 'conventional' therapy in which a mixture of short and long acting insulin is given in the morning and then again before the evening meal. Insulin is either drawn up from different bottles into the same syringe or use the pre-mixed insulin (disposable pen injectors). One plus point of this regimen is that there is no need of insulin shot at lunch and dinner time, but it becomes very essential to maintain timings of each meal. And, delaying or skipping of any meal will be oblivious cause of hypoglycemia. Lack of flexibility is again a problem if, a pre-mixed insulin is used as it is harder to vary the insulin dose according to the changes in your daily routine. The doses of short and long acting insulin cannot be varied independently of one another. This regimen works as follow:

the morning short acting insulin takes care of breakfast the morning long acting insulin takes care of lunch the evening short acting insulin takes care of the evening meal the evening long acting insulin takes care of overnight insulin needs

2. Multiple daily injections of short or fast acting insulin with one or two separate injections of intermediate or long acting insulin This type of regimen is termed as 'intensive' or 'flexible' insulin therapy. Short or fast acting insulin is given before meals and long acting insulin is given at bedtime. Although a lunchtime injection is usually required, the use of a pen injector can make it a quick and easy task. This insulin regimen is much more flexible especially for mealtimes. It can easily accustom according to the body's natural needs, by providing constant supply. This regimen work as follows:

the short or fast acting insulin takes care of meals the long acting insulin takes care of background insulin needs
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There are many things which can affect how the insulin is absorbed from the injection site into the bloodstream. It includes: Mode of administration Selecting the 'right' dose and timing Selecting a suitable insulin preparation (typically on 'speed of onset and duration of action' grounds) Adjusting dosage and timing to fit food intake timing, amounts, and types Adjusting dosage and timing in accordance with exercise undertaken Adjusting dosage, type and timing according to other conditions like stress, illness etc The dosage is non-physiological in that a subcutaneous bolus dose of insulin alone is administered instead of combination of insulin It is dangerous in case of mistake (Hypoglycemia or Hyperglycemia) Once open insulin may be preserved for 30 days at temperature less than 86 F.

Good control of blood glucose levels is always important for your health. Proper insulin supervision will help you to take control of your diabetes. It will also help you to fit the diabetes into your life rather than trying to fit your life around the diabetes. Insulin is classified according to how long it is effective in the body. There are five different types of insulins ranging from short to long acting. Some insulins are clear in appearance, while others are cloudy. Diabetics need varying amounts of both short and long acting insulin as everyone is different and will respond differently to the insulin they take. Lets see the classification of different types of insulin Rapid onset-fast acting insulin: It is fast acting so starts working within one to 20 minutes. It is clear in appearance and its peak time is about one hour later and lasts for three to five hours. When you inject rapid onset-fast acting type of insulin, you must eat immediately after you inject. The two rapid onset-fast acting insulin types currently available are:

Novo Rapid (Insulin Aspart) Humalog (Lispro)

Short acting insulin: It looks clear and begins to lower blood glucose levels within 30 minutes, so you need to take your injection half an hour before eating. Short acting insulin has peak effect of four hours and works for about six hours. Short acting insulin types, currently available include:

Actrapid Humulin Hypurin Neutral (bovine - highly purified beef insulin)

Intermediate acting insulin:- Intermediate acting insulin looks cloudy. They have either protamine or zinc added to delay their action. This insulin starts to show its effect about 90
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minutes after you inject, peak at 4 to 12 hours and lasts for 16 to 24hours. Intermediate acting insulins presently available with protamine:

Protaphane Humulin NPH Hypurin Isophane (bovine)

Mixed insulin: Mixed insulin is cloudy in appearance. It is a combination of either a rapid onsetfast acting or a short acting insulin and intermediate acting insulin. Advantage of it is that, two types of insulin can be given in one injection. When it shows 30/70 then it means 30% of short acting is mixed with 70%of intermediate acting insulin. Note: - Roll or shake well the vial of insulin in order to mixed them evenly. The mixed insulins currently available include:

NovoMix30 Humalog Mix 25 Mixtard 30/70 Mixtard 20/80

Long acting insulin: There are two kinds of long acting insulin available in market, both with clear appearance. Lantus (Glargine) - It has no peak period as it works constantly when released into your bloodstream at a relatively constant rate. (full 24 hours) Levemir (Detemir) - It has a relatively flat action, can last up to 24 hours and may be given once or twice during the day.

Modes of administration Unlike many medicines, insulin cannot be taken orally at the present time. Like nearly all other
proteins introduced into the gastrointestinal tract, it is reduced to fragments (even single amino acid components), whereupon all 'insulin activity' is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered in a pill. So far this is entirely experimental.

Subcutaneous
Insulin is usually taken as subcutaneous injections by single-use syringes with needles, an insulin pump, or by repeated-use insulin pens with needles. Patients who wish to reduce repeated skin puncture of insulin injections often use an injection port in conjunction with syringes. Administration schedules often attempt to mimic the physiologic secretion of insulin by the pancreas. Hence, both a long-acting insulin and a short-acting insulin are typically used.

Insulin pump
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Insulin pumps are a reasonable solution for some. Advantages to the patient are better control over background or 'basal' insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that may help with determining 'bolus' infusion dosages. The limitations are cost, the potential for hypoglycemic and hyperglycemic episodes, catheter problems, and no "closed loop" means of controlling insulin delivery based on current blood glucose levels. Insulin pumps may be like 'electrical injectors' attached to a temporarily implanted catheter or cannula. Some who cannot achieve adequate glucose control by conventional (or jet) injection are able to do so with the appropriate pump. As with injections, if too much insulin is delivered or the patient eats less than he or she dosed for, there will be hypoglycemia. On the other hand, if too little insulin is delivered, there will be hyperglycemia. Both can be life-threatening. In addition, indwelling catheters pose the risk of infection and ulceration, and some patients may also develop lipodystrophy due to the infusion sets. These risks can often be minimized by keeping infusion sites clean. Insulin pumps require care and effort to use correctly. However, some patients with diabetes are capable of keeping their glucose in reasonable control only with an insulin pump.

Inhalation
Main article: Inhalable insulin

In 2006 the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin.[13] It has been withdrawn from the market by its maker as of 3Q 2007, due to lack of acceptance. Inhaled insulin claimed to have similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short acting and is typically taken before meals; an injection of long-acting insulin at night is often still required. When patients were switched from injected to inhaled insulin, no significant difference was observed in HbA1c levels over three months. Accurate dosing was a particular problem, although patients showed no significant weight gain or pulmonary function decline over the length of the trial, when compared to the baseline. Following its commercial launch in 2005 in the UK, it was not (as of July 2006) recommended by National Institute for Health and Clinical Excellence for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist". In January 2008, the world's largest insulin manufacturer, Novo Nordisk A/S, also announced that the company was discontinuing all further development of the company's own version of inhalable insulin, known as the AERx iDMS inhaled insulin system. Similarly, Eli Lilly and Company ended its efforts to develop its Air inhaled insulin in March 2008. However, MannKind Corp. (whose majority owner, Alfred E. Mann), remains optimistic about the concept.

Transdermal
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There are several methods for transdermal delivery of insulin. Pulsatile insulin uses microjets to pulse insulin into the patient, mimicking the physiological secretions of insulin by the pancreas. Jet injection had different insulin delivery peaks and durations as compared to needle injection. Some diabetics find control possible with jet injectors, but not with hypodermic injection. Both electricity using iontophoresis and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental, but the blood glucose test aspect of 'wrist appliances' is commercially available. Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin.

Intranasal insulin
Intranasal insulin is being investigated.

Oral insulin
The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. However, insulin is a protein, which is digested in the stomach and gut and in order to be effective at controlling blood sugar, can not be taken orally in its current form. The potential market for an oral form of insulin is assumed to be enormous, thus many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. As of 2004, no products appear to be successful enough yet to bring to market. Novo Nordisk announced on December 7, 2009, that it had initiated its first phase 1 trial with oral insulin analogue (NN1952). The aim of the trial is to investigate the safety, tolerance, pharmacokinetics (exposure to drug) and pharmacodynamics (effect) of NN1952 in healthy volunteers and people with type 1 and type 2 diabetes. Results from the trial, which is planned to enroll about 80 people, are expected to be reported in the first half of 2011. NN1952 has been designed to address some of the key challenges relating to oral insulin delivery. Furthermore, it uses the GIPET (R) formulation technology from Merrion Pharmaceuticals (IEX Quoted) to facilitate insulin absorption from the gut. In November 2008, Merrion entered into a development and license agreement to develop and commercialise oral formulations of Novo Nordisk's proprietary insulin analogues, using Merrion's proprietary GIPET (R). A Connecticut-based biopharmaceutical company called Biodel, Inc. is developing what it calls VIAtab, an oral formulation of insulin designed to be administered sublingually. This therapy is a tablet that dissolves in minutes when placed under the tongue. In a Phase I study, VIAtab delivered insulin to the blood stream quickly and resembled the first-phase insulin release spike found in healthy individuals. The company claims that an oral insulin therapy would be more convenient than currently available injectable or inhalable therapies, and they expect that convenience to result in increased insulin usage among the currently underserved early-stage

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patients with Type 2 diabetes, thus helping to create better long-term outcomes for that patient population. Oramed Pharmaceuticals, Inc., a biotechnology company based in Jerusalem, Israel, is currently conducting Phase 2B clinical trials of its oral insulin capsule, ORMD-0801, on 30 patients diagnosed with type 2 diabetes. An article published in the Journal of Diabetes Science and Technology indicates that Oramed's platform technology has two components: 1) A chemical make-up that protects insulin during passage through the gastrointestinal tract, and 2) absorption enhancers so that insulin could be absorbed by the intestine. Oramed Pharmaceuticals, Inc. through Phase 1 clinical trials, has demonstrated that its oral insulin is safe, well tolerated, and has consistently reduced glucose and c-peptide levels in patients. Australian biopharmaceutical company Apollo Life Sciences plans to enter the phase I trial of its oral insulin tablet in mid-2008. Biocon, Asia's largest biopharmaceutical company, based in Bangalore, India, is also developing an oral insulin product. It has recently entered phase III trials; the company hopes to launch their product, IN-105, in 2011.

Pancreatic transplantation
Main article: Islet cell transplantation

Another improvement would be a transplantation of the pancreas or beta cell to avoid periodic insulin administration. This would result in a self-regulating insulin source. Transplantation of an entire pancreas (as an individual organ) is difficult and relatively uncommon. It is often performed in conjunction with liver or kidney transplant, although it can be done by itself. It is also possible to do a transplantation of only the pancreatic beta cells. However, islet transplants had been highly experimental (read 'prone to failure') for many years, but some researchers in Alberta, Canada, have developed techniques with a high initial success rate (about 90% in one group). Nearly half of those who got an islet cell transplant were insulin-free one year after the operation; by the end of the second year that number drops to about one in seven. However, researchers at the University of Illinois at Chicago (UIC) have slightly modified the Edmonton Protocol procedure for islet cell transplantation and achieved insulin independence in diabetes patients with fewer but better-functioning pancreatic islet cells. Longer-term studies are needed to validate whether it improves the rate of insulin-independence. Beta cell transplant may become practical in the near future. Additionally, some researchers have explored the possibility of transplanting genetically engineered non-beta cells to secrete insulin. Clinically testable results are far from realization at this time. Several other non-transplant methods of automatic insulin delivery are being developed in research labs, but none is close to clinical approval.

Dosage and timing


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The dosage units


The unit of measurement used in insulin therapy is, remarkably, not part of the International System of Units (abbreviated SI from the French le Systme international d'unit) which is the modern form of the metric system. Instead the pharmacological international unit (IU) is defined by the WHO Expert Committee on Biological Standardization. One international unit of insulin (1 IU) is defined as the biological equivalent of about 45.5 g pure crystalline insulin (1/22 mg exactly). This corresponds to the old USP insulin unit, where one unit (U) of insulin was (arbitrarily) set equal to the amount required to reduce the concentration of blood glucose in a fasting rabbit to 45 mg/dl (2.5 mmol/L).

The problem

Diagram explaining the basal-bolus insulin schedule. The long acting insulin is given once (usually glargine, Lantus) or twice (usually detemir, Levemir) daily to provide a base, or basal insulin level. Rapid acting (RA) insulin is given before meals and snacks. A similar profile can be provided using an insulin pump where rapid acting insulin is given as the basal and premeal bolus insulin. The central problem for those requiring external insulin is picking the right dose of insulin and the right timing. Physiological regulation of blood glucose, as in the non-diabetic, would be best. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. The increased insulin level causes glucose absorption and storage in cells, reduces glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. The result is that the blood glucose level rises somewhat after eating, and within an hour or so, returns to the normal 'fasting' level. Even the best diabetic treatment with synthetic human insulin or even insulin analogs, however administered, falls far short of normal glucose control in the nondiabetic. Complicating matters is that the composition of the food eaten (see glycemic index) affects intestinal absorption rates. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. In addition, fats and proteins cause delays in absorption of glucose from carbohydrates eaten at the same time. As well, exercise reduces the need for insulin even when all other factors remain the same, since working muscle has some ability to take up glucose without the help of insulin.

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Because of the complex and interacting factors, it is, in principle, impossible to know for certain how much insulin (and which type) is needed to 'cover' a particular meal to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetics' beta cells routinely and automatically manage this by continual glucose level monitoring and insulin release. All such decisions by a diabetic must be based on experience and training (i.e., at the direction of a physician, PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the patient. But it is not straightforward and should never be done by habit or routine. With some care however, it can be done reasonably well in clinical practice. For example, some patients with diabetes require more insulin after drinking skim milk than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form. Their particular reaction to skimmed milk is different from other people with diabetes, but the same amount of whole milk is likely to cause a still different reaction even in that person. Whole milk contains considerable fat while skimmed milk has much less. It is a continual balancing act for all people with diabetes, especially for those taking insulin. Patients with insulin-dependent diabetes typically require some base level of insulin (basal insulin), as well as short-acting insulin to cover meals (bolus insulin). Maintaining the basal rate and the bolus rate is a continuous balancing act that people with insulin-dependent diabetes must manage each day. This is normally achieved through regular blood tests, although continuous blood sugar testing equipment (Continuous Glucose Monitors or CGMs) are now becoming available which could help to refine this balancing act once widespread usage becomes common.

Strategies
A long-acting insulin is used to approximate the basal secretion of insulin by the pancreas. NPH/isophane, lente, ultralente, glargine, and detemir may be used for this purpose. The advantage of NPH is its low cost and the fact that you can mix it with short-acting forms of insulin, thereby minimizing the number of injections that must be administered. The disadvantage is that the activity of NPH is less steady and will peak 46 hours after administration, and this peak has the potential of causing hypoglycemia. NPH and regular insulin in combination are available as premixed solutions, which can sometimes simplify administration. The theoretical advantage of glargine and detemir is that they only need to be administered once a day, and they also have steady activity, generally without peaks, although in practice, many patients find that neither lasts a full 24 hours. Glargine and detemir are also significantly more expensive, and they cannot be mixed with other forms of insulin. A short-acting insulin is used to simulate the endogenous insulin surge produced in anticipation of eating. Regular insulin, lispro, aspart and glulisine can be used for this purpose. Regular insulin should be given with about a 30 minute lead-time prior to the meal to be maximally effective and to minimize the possibility of hypoglycemia. Lispro, aspart and glulisine are approved for dosage with the first bite of the meal, and may even be effective if given after completing the meal. The short-acting insulin is also used to correct hyperglycemia. The usual schedule for checking fingerstick blood glucose and administering insulin is before all meals and sometimes also at bedtime. More recent guidelines also call for a check 2 hours after a
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meal to ensure the meal has been 'covered' effectively. When insulin glargine or insulin detemir is used, it can be administered at any time during the day, provided that it is given at the same time every day. Sliding scales Insulin prescriptions generally specify fixed amounts of long-acting insulin to be given routinely, and fixed amounts of short-acting insulin prior to every meal (the 'sliding scale' approach). However, the amount of short-acting insulin may be varied depending on the patient's preprandial fingerstick glucose, in order to correct pre-existing hyperglycemia. The so-called "sliding-scale" is still widely taught, although it is controversial. It was first described in 1934. Sample regimen using insulin NPH and regular insulin
before breakfast before lunch before dinner at bedtime

NPH dose

12 units

6 units

regular insulin fingerstick glucose is [mmol/L]:

dose

if

(mg/dl)

70-100

[3.9-5.5]

4 units

4 units

101-150

[5.6-8.3]

5 units

5 units

151-200

[8.4-11.1]

6 units

6 units

201-250

[11.2-13.9]

7 units

7 units

251-300

[14.0-16.7]

8 units

1 unit

8 units

1 unit

>300

[>16.7]

9 units

2 units

9 units

2 units

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Sample regimen using insulin glargine insulin lispro to be given as follows:


if fingerstick glucose before is (mg/dl) breakfast [mmol/L]:

insulin 20

glargine units

and at

insulin

lispro bedtime

before lunch

before dinner

at bedtime

70-100 5.5]

[3.9-

5 units

5 units

5 units

101-150 8.3]

[5.6-

6 units

6 units

6 units

151-200 11.1]

[8.4-

7 units

7 units

7 units

201-250 13.9]

[11.2-

8 units

8 units

8 units

1 unit

251-300 16.7]

[14.0-

9 units

9 units

9 units

2 units

>300 [>16.7]

10 units

10 units

10 units

3 units

Carb counting and DAFNE A more complicated method that allows greater freedom with meal times and snacks is "carb counting." This approach is taught to diabetic patients in Europe as "Dose Adjustment For Normal Eating" or DAFNE. In Europe, patients that are not familiar with the DAFNE regime can take an educational course where the basic starting insulin dose guideline is "for every 10g of carbohydrates you eat, take 1 unit of insulin". DAFNE courses also cover topics that naturally work along side this regime,

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such as blood glucose monitoring, exercise and carbohydrate estimation to help the patient work out their personal control requirements. The patient also can use his or her total daily dose (TDD) of insulin to estimate how many grams of carbohydrates will be "covered" by 1 unit of insulin, and using this result, the patient can estimate how many units of insulin should be administered depending on the carbohydrate concentration of their meal. For example, if the patient determines that 1 unit of insulin will cover 15 grams of carbohydrates, then they must administer 5 units of insulin before consuming a meal that contains 75 grams of carbohydrates. Some alternative methods also consider the protein content of the meal (since excess dietary protein can be converted to glucose via gluconeogenesis). With DAFNE, most dosages involve a fair degree of guesswork, especially with non-labeled foods, and will only work fairly consistently from one dosage to the next if the patient is aware of their body's requirements. For example, a patient finds they can take 1 unit to 10g of carbohydrates in the morning and the evening, but find that their body requires more insulin for a meal in the middle of the day so they have to adjust to 1 unit per 8.5g of carbohydrates. You also have to factor in that things like a hot day can effect how your body uses the insulin. Using the hot day as an example, some patients may find that their bodies process insulin much better on these days so require less insulin. With this, the patient again has to adjust their dose to the best of their understanding from their past experiences. Unfortunately, because the DAFNE regime requires the patient to learn about their body's needs through experience, it can be a very frustrating process to take on, but the results can be worthwhile in the long term.

Dietary control of insulin


Many popular weight-loss regimes claim to manipulate weight gain forcing insulin levels (often characterized as insulin overload) by control of carbohydrate intake. Insulin release is controlled by several factors; the carbohydrate stimulus is blood glucose which is not produced by all kinds of carbohydrate. Some types of amino acids also stimulate insulin release. In addition, overly high levels of insulin are seen only in those with pathologies such as Type 2 diabetes mellitus, and only in some of those. The typical person cannot have insulin overload and still have blood glucose levels which do not force symptoms of hypoglycemia. In the non-diabetic, the feedback control mechanism connecting insulin release and blood glucose level is very effective, and it is not possible to adjust it except that blood glucose levels rise slightly during digestion and absorption of glucose. The decrease in blood glucose levels is directly attributable to release of insulin, and that release ceases as blood glucose levels drop. On the other hand, prolonged abnormally low levels of insulin, if it were possible to produce them by control of diet composition and amount, would produce problems with electrolyte balance and with amino acid uptake in cells, among many other effects.

Structure of Insulin
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Insulin is composed of 2 peptide chains i.e. A chain and B chain. Both the chains are linked together by two disulfide bonds, and one disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids that means it is composed of 51 amino acids in two peptide chains (A and B). The three-dimensional structure of insulin molecule (insulin monomer) exists in two main conformations. These differ in the extent of helix in the B chain due to phenol or its derivatives. In acid solutions, the insulin monomer assembles as dimmers (diffuses in the blood) neutral pH and in the presence of zinc ions, as hexamers. The intermediate and long acting insulin has high proportion of hexamers, to delay its action. The sequence of amino acid in insulin varies among species, certain segments are conserved, like positions of the three disulfide bonds, both ends of the A chain and the C-terminal residues of the B chain. These similarities in the amino acid sequence of insulin lead to a three dimensional conformation of insulin that is very similar among species, and insulin from one animal is very likely biologically active in other species. Indeed, pig insulin has been widely used for human.

The first of these molecules to be marketed - called insulin lispro - is engineered such that lysine and proline resting on the C-terminal end of the B chain are reversed; this modification does not alter receptor binding, but minimizes the tendency to form dimmers and hexamers.

Types of Insulin
Good control of blood glucose levels is important for your health, now and in the future. Understanding your insulin treatment will help you to control diabetes. It will also help you to fit the diabetes into your life, instead of trying to fit your life around the diabetes. There are more than 20 types of insulin products available in four basic forms, each with a different time of onset and duration of action. The decision as to which insulin to choose is based on an individual's lifestyle, blood sugar level and a physician's preference and experience. Criterions to be considered in choosing insulin are:

Onset:- how soon it starts working.


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Peak time:- when it works the hardest. Duration:- how long it lasts in the body.

Obesity affects the work of insulin in the body. If body has extra fat tissue, then it will be more resistant to insulin. Treatment for Type 1 diabetes most likely includes insulin via injections, inhaled insulin or an insulin pump. Your physician will recommend the appropriate insulin treatment and its delivery mechanism, in respect to individual case. Insulin was prepared from bovine (beef) and porcine (pork) sources. Beef and pork insulin is no longer available in the United States. Instead, recombinant (human) insulin is used and marketed. Insulin cant be taken by mouth because it would be destroyed by digestion, so it is administered subcutaneous by syringe. Since 1982, most of the newly approved insulin preparations have been produced by inserting portions of DNA ("recombinant DNA") into special lab-cultivated bacteria or yeast. This process allows the bacteria or yeast cells to produce complete human insulin. Recombinant human insulin has, for the most part, replaced animal-derived insulin, such as pork and beef insulin. Regular insulin acts within 30 minutes and its effect lasts for 6 to 8 hours. The maximal effect occurs 1 to 3 hours following the injection. As compared to regular insulin, insulin lispro acts more rapidly, has an earlier maximal effect and a shorter duration action. Therefore, insulin lispro should be given within 15 minutes of a meal, compared to regular insulin, which is given 30-60 minutes before meals. Nowadays people with diabetes no longer need needles or shots to take insulin, as researchers have prepared new ways to get insulin into the bloodstream which can be just inhaled. In January 2006, the FDA approved inhaled insulin, started as a treatment option for Type 1 and Type 2 diabetes. This new type of insulin, available by the name Exubera, comes in powder form and is the first new insulin delivery option since the discovery of the hormone in the 1920s.

Insulin Synthesis
Insulin is synthesized as a preprohormone in the beta cells of the islets of Langerhans. Its signal peptide is removed in the cisternae of the endoplasmic reticulum and then packaged into secretory vesicles in the Golgi. It is folded in its native structure and locked in this conformation by, the formation of 2 disulfide bonds. In normal individual, insulin is produced by the body in response to the rise in blood glucose level. Apart from it, spurts of insulin are produced throughout the day and night, to look after the body resting needs for insulin and ensure that cells can take up glucose. In other words, function of insulin is to counter the concerted action of the numerous hyperglycemia generating hormones and to sustain low blood glucose levels. There are numerous hyperglycemic hormones untreated disorders associated with
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insulin, generally leading to severe hyperglycemia and a shortened life span. In people with type 1 diabetes, the pancreas no longer release the insulin as the beta cells are destroyed and they need insulin shots to use glucose from meals. People with type 2 diabetes can produce insulin but, their body doesn't respond well to it. Some people with type 2 diabetes need diabetes pills or insulin dosages to utilize glucose for energy generation. Insulin cannot be taken as a pill as it will be break down during digestion just like the protein in food. Insulin must be injected into the fat under your skin, to make it get into your blood. By reducing the concentration of glucose in the blood, insulin is thought to prevent or reduce the long-term complications of diabetes, including damage to the blood vessels, eyes, kidneys, and nerves.

Diabetes and Insulin Analogs


A short time ago insulin products called "insulin analogs" have been formed so that the structure differs slightly from human insulin, (with respect of amino acids) to change onset and peak of action. People with Type 1 diabetes usually need a combination of different types of insulin in order to control blood sugar with ease. The following table lists some of the more common insulin preparations available today. Onset, peak, and duration of action are approximate for each insulin product, as there may be variability depending on each individual, the injection site and the individual exercise program Types Insulin of Examples Humalog (lispro) Eli Lilly NovoLog (aspart) Novo Nordisk Onset of Peak Action Action 15 minutes 30-90 minutes of Duration of Action

3-5 hours

Rapid-acting

15 minutes

40-50 minutes

3-5 hours

Short-acting (Regular)

Humulin R Eli Lilly 30-60 Novolin R minutes Novo Nordisk

50-120 minutes

5-8 hours

Intermediate- Humulin N 1-3 hours 8 hours acting (NPH) Eli Lilly Novolin N Novo Nordisk

20 hours

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Humulin L Eli Lilly 1-2.5 Novolin L hours Novo Nordisk

7-15 hours

18-24 hours

Mixed acting

Humulin 50/50 Humulin 70/30 Humalog Mix The onset, peak, and duration 75/25 of action of these mixtures Humalog Mix would reflect a composite of 50/50 the intermediate and short- or Eli Lilly rapid-acting components, with Novolin 70/30 one peak of action. Novolog Mix 70/30 Novo Nordisk Ultralente Eli Lilly 4-8 hours 8-12 hours 36 hours

Long-acting

Lantus (glargine) Aventis

1 hour

None

24 hours

Diabetes Treatment and Insulin Problems

There are many things which can affect how the insulin is absorbed from the injection site into the bloodstream. It includes:

Mode of administration Selecting the 'right' dose and timing


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Selecting a suitable insulin preparation (typically on 'speed of onset and duration of action' grounds) Adjusting dosage and timing to fit food intake timing, amounts, and types Adjusting dosage and timing in accordance with exercise undertaken Adjusting dosage, type and timing according to other conditions like stress, illness etc The dosage is non-physiological in that a subcutaneous bolus dose of insulin alone is administered instead of combination of insulin. It is dangerous in case of mistake (Hypoglycemia or Hyperglycemia) Once open insulin may be preserved for 30 days at temperature less than 86 F.

Can Diabetes Be Cured?


Diabetes is an insidious disease. In fact, moderately high levels of blood glucose (180200 mg/dl) produce no symptom and may go unnoticed for many months or even years. Most patients with Type 1 diabetes pass large volumes of urine, experience an increase in the frequency of urination, undue thirst and hunger, and rapid weight loss. These symptoms provide clues to the diagnosis of diabetes. Men and women with Type-2 diabetes may not have the above symptoms. Some of them may experience an increase in the frequency of urination and abnormal thirst. They may however feel tired, irritable, lack concentration at work, proneness to infection, delay in wound healing, intense itching and need for frequent change of eye glasses. At the age of 45yrs or later, if you foresee the risk of developing diabetes, get your fasting blood glucose test, 2-hrs after a drink of 3.527 oz of glucose, at least once a year. Blood glucose values of 200mg/dl and higher would suggest the diagnosis of diabetes mellitus. Can diabetes be cured? Diabetes cannot be cured completely, but can be effectively controlled. People with diabetes can lead a healthy life if, their blood glucose level is under control. The decrease in life span of a diabetic is restored to normal by maintaining good blood glucose control (90-130 mg/dl at fasting and with less than 180 mg/dl 2hrs after meals). Sometimes, patients may not need any tablet/insulin or, even diet control to keep their blood glucose in control. This period is called honeymoon phase (in Type-1 diabetes). The duration may vary from a few days to over six months. Some patients mistake this for cure of diabetes. Cardiovascular disease accounts for 70-75% deaths in diabetic people with acute myocardial infarction being responsible for 30% mishaps. Diabetes typically doubles
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heart attack risk in men and triples in women. Diabetes causes more extensive coronary atherosclerosis with triple vessel involvement. Long-duration diabetes and diabetes in elderly people is more likely to cause silent heart attack (painless MI) with increased chances of death.

Diabetes Mellitus Medications for Diabetes Mellitus Sulfonylureas: first choice for normal weight; hypoglycemia with monotherapy - stimulate insulin secretion in response to glucose. Watch for weight gain.

Glipizide (Glucotrol) Dose: lowest effective single dose, 5mg, Usually dose 5-10 mg 1-2 tab BID (Max 40 mg/day) Glipizide (GI therapeutic system) Glucotrol XL 5-10mg tab once/day (Max 20 mg/day) Dose: lowest effective single dose, 5 mg; daily max, 20 mg Glyburide (Micronase, Diabeta) - (2nd generation) Dose: lowest effective single dose, 1.25 mg; Usually dose 1.25-2.5-5 mg 1-2 tab BID (Max 20 mg/day) Micronized glyburide (Glynase) Dose: lowest effective single dose, 1.5 mg; daily max, 6 mg Glimepiride (Amaryl) (3rd generation) Dose: lowest effective single dose, 0.5 mg; 1,2,4 mg tab/day. Start 1-2 mg/d, usual maintenance dose is 1-4mg once/d (Max: 8mg/d) Gliclazide/ Diamicron 80-160 mg daily, max 320 mg PO daily. Modified release Diamicron MR 30 mg PO daily, mas 120 mg daily Combination meds: Glucovance (Glyburide and Metformin) Avandaryl (Glimepiride and Avandia/Rosiglitazone) Diabenese/Chlorpropamide (1st generation) 100-250 mg 1-3 tab/d; 100-250 mg tab Orinase /Tolbutamide (1st generation) 250-500 mg tab 1-3x/d Tolinase/Tolazamide (1st generation)
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100-500 mg tab -2x/d; 100-250-500 mg tab. Dymelor/Acetohexamide 500-750 mg once or divided.

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin (Exubera) Biguanides - Primary action is reduction of excessive hepatic glucose output; it also has some activity on insulin resistance in skeleton muscle, though less than troglitazone. - Metformin may cause life-threatening lactic acidosis. - Takes about 2 wks to work well. Do not use in renal or hepatic dysfunction, dehydrated, or hospital patients. - Hold this med prior to IV contrast agents and for for 48 hours after. - Avoid if ethanol abuse, heart failure, hepatic or renal insufficiency (Cr >1.4-1.5), or hypoxic states.

Metformin: first choice for obese Dose: 500 - 850 mg tab 2-3x/day or 1000 mg bid with meals. (MAX 2550 mg/day) Glumetza/ Extended Metformin 500-1,000 mg dosage strength Glucovance (Glyburide and Metformin) Avandamet (Avandia/Rosiglitazone and Metformin) Janumet (Januvia/Sitagliptin and Metformin)

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin (Exubera) Thiazolidinediones TZD (Glitazones) - enhance insulin action (sensitivity to insulin) in muscle, adipose tissue & liver; it also reduces excessive hepatic glucose output. It is for type II diabetes currently on insulin, yet not controlled (insulin >30 u/d) . - Side effects are weight gain and edema. Caution: Possible liver damage. Check LFT baseline & then every 1-2 months when clinically indicated thereafter.

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Pioglitazone/Actos 15-30-45 mg tablet once daily (Max 45 mg/day) Rosiglitazone/Avandia 4 mg 1-2x/day (Max 8 mg/day) - see warning below! Avandamet (Rosiglitazone/metformin) 1-2-4 mg/500mg tablets * NEJM May 2007;356:1 In the rosiglitazone (Avandia) group, as compared with the control group, the odds ratio for myocardial infarction was 1.43 (as 0.43% vs 0.36% in small trials, 0.57% vs 0.34% in DREAM trial, 1.85% vs 1.44% in ADOPT trial), and for death from cardiovascular causes was 1.64 (as 0.38% vs 0.19% in small trials, 0.51% vs 0.38% in DREAM trial, 0.14% vs 0.18% in ADOPT trials). Troglitazone/Rezulin -200-400mg tab 1/d - discontinued!

__________________________________ Study continues controversy over rosiglitazone (Avandia)'s cardiovascular risks 6-8-2009 A new study found that rosiglitazone doubled the risk of heart failure among type 2 diabetes patients but did not raise overall cardiovascular hospitalizations or deaths compared with standard therapy. The manufacturer-sponsored Rosiglitozone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes, or RECORD, trial's results conflict with the findings of a 2007 study showing that rosiglitazone significantly increased the risk of myocardial infarction. The RECORD trial confirmed, however, earlier findings that rosaglitazone doubles the risk of distal fracture in older women. The study results were presented at the American Diabetes Association's annual scientific sessions over the weekend and published online by the Lancet (The Lancet, Early Online Publication, 5 June 2009doi:10.1016/S0140-6736(09)609533). [Findings: 321 people in the rosiglitazone group and 323 in the active control group experienced the primary outcome during a mean 55-year follow-up, meeting the criterion of non-inferiority (HR 099, 95% CI 085116). HR was 084 (059118) for cardiovascular death, 114 (080163) for myocardial infarction, and 072 (049106) for stroke. Heart failure causing admission to hospital or death occurred in 61 people in the rosiglitazone group and 29 in the active control group (HR 210, 135327, risk difference per 1000 person-years 26, 1141). Upper and distal lower limb fracture rates were increased mainly in women randomly assigned to rosiglitazone. Mean HbA1c was lower in the rosiglitazone group than in the control group at 5 years.] In the trial, 4,447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean hemoglobin A1c of 7.9% were randomly assigned to either add rosiglitazone to their existing regimen or take metformin and sulfonylurea alone. After 5.5 years follow up, HbA1c was lower in the rosiglitazone group than the standard therapy group, rosiglitazone did not increase the risk of overall cardiovascular morbidity or mortality, and rosiglitazone patients had a nonsignificant reduction in fatal and nonfatal stroke. However, heart failure causing admission to hospital or death was higher in the intervention group (hazard ratio [HR] 2.10; 95% confidence interval [CI] 1.35-3.27; risk difference per 1,000 person-years HR 2.6; CI 1.1-4.1) and upper and
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distal lower limb fracture rates were increased mainly in women taking rosiglitazone. The authors concluded that the data are inconclusive about rosiglitazone's effects on myocardial infarction and that the drug does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose lowering drugs. In an interview with Modern Medicine, a study author noted that rosiglitazone should not be used by patients who have heart failure or who are at increased risk of fracture but could be considered in other type 2 diabetics, particularly obese patients. Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin (Exubera) Meglitinides(Non-Sulfonylurea Insulin Secretagogues) - stimulate insulin production in response to post-meal hyperglycemia. - Side effects include hypoglycemia, while repaglinide can bring on headaches.

Prandin (Repaglinide) 0.5 - 1 - 2 mg tab TID within 30 min before meals (Max 16 mg/day) Starlix (Nataglinide) 120 mg ac

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin Alpha-glucosidase Inhibitor - induce gastrointestinal carbohydrate absorption after a meal. - it delays the breakdown of complex carbohydrates in the intestine & reduces the postprandial rise in blood glucose. - least effective; must be taken at start of meals - Side effects include bloating, GI upset, pain, flatulence, and diarrhea.

Acarbose/Precose 25- 50- 100 mg tid with first bite of meal. Initially 25 mg 1x/d x2wks, then bid x2wks,
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then tid x2months, then may increase to 50 mg tid.. Miglitol/Glyset 25-50-100 mg tid with first bite of meal. (Max 300 mg/day)

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin GLP (Glucagon-Like Peptide) Analogues: Byetta (Exenatide) 5 mcg subc bid - 5 mcg subc bid, within 1 h before the morning & evening meals, may increase to 10 mcg bid subc after 1 month. - It is available in a pen that delivers 60 fixed doses of either 5 mcg or 10 mcg for 1 month supply. - It is a long-acting analogue of gut incretin hormone GLP-1 (Glucagon-like-peptide-1), called incretin mimetics (analog) for the treatment of type 2 diabetes (Not approved for type 1 diabetes). - It exhibits many of the same effects as GLP-1, secreted in response to food intake, has multiple effects on the stomach, liver, pancreas and brain that work in concert to regulate blood sugar. - It reduces fasting & postprandial glucose by increasing glucose-stimulated insulin secretion, decreasing glucagon secretion, slowing gastric emptying & reducing appetite. - Nausea is a frequent side effect (44%), vomiting & diarrhea (13%); potential hypoglycemia. - An association between Byetta & acute pancreatitis, even fatal case, is suspected in some of these cases. (Precaution) - It may be used in combination with metformin, sulfonylurea or both. * More than 80% of treated patients with Byetta (Exenatide) lost weight 3-5 lbs at 30 weeks . Amylin Analogues: Symlin (pramlintide) 15 mcg subc before meal 15 mcg subc before meal, titrate by 15 mcg increments up to maintenance 30-60 mcg as tolerated in Type 1 diabetes. - In type 2 diabetes initiate 60 mcg subc before meals and increase upto 120 mcg as tolerated. - a synthetic analog of the pancreatic neuroendocrine hormone amylin, it is secreted from beta cells with insulin.
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- The drug slows gastric emptying and decreases appetite and glucagon secretion after meals.

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Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase)


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| Biguanides
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(Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin (Exubera) DPP IV Inhibitors DDP-4 enzyme naturally breaks down the GI hormone called GLP-1 (Glucagon-Like Peptide), which promotes the synthesis and release of insulin when food is consumed, lowers levels of glucagon, induces satiety by slowing gastric emptying, and possibly stimulates beta-cell growth & neogenesis.

Vildagliptin (Galvus, Novartis) Sitagliptin (Januvia, Merck) - approved October 2006

Januvia (Sitagliptin) - recommended dose of JANUVIA is 100 mg PO once daily JANUVIA (sitagliptin phosphate), the first and only a new breakthrough class of DPP-4 inhibitor available in the United States for the treatment of type 2 diabetes, as monotherapy and as add-on therapy to either of two other types of oral diabetes medications, metformin or thiazolidinediones (TZDs), to improve blood sugar (glucose) control in patients with type 2 diabetes when diet and exercise is not enough. JANUVIA enhances a natural body system called the incretin system, which helps to regulate glucose by affecting the beta cells and alpha cells in the pancreas. Through DPP-4 inhibition, JANUVIA works only when blood sugar is elevated to address diminished insulin due to betacell dysfunction and uncontrolled production of glucose by the liver due to alpha-cell and betacell dysfunction.

Helps control glucose without weight gain or an increased risk of hypoglycemia JANUVIA is indicated, as an adjunct to diet and exercise, as monotherapy to improve glycemic control in patients with type 2 diabetes mellitus. The recommended dose of JANUVIA is 100 mg once daily, with or without food, as monotherapy or as combination therapy with metformin or a TZD as an adjunct to diet and exercise for type 2 diabetes. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. A dosage adjustment is recommended in patients with moderate or severe renal insufficiency or with end-stage renal disease(ESRD) requiring hemodialysis or peritoneal dialysis. The use of JANUVIA in combination with medications known to cause hypoglycemia, such as sulfonylureas or insulin, has not been adequately studied. Research is ongoing. The incidence of selected gastrointestinal (GI) adverse reactions in patients treated with JANUVIA 100 mg vs placebo was as follows: abdominal pain (2.3%, 2.1%); nausea (1.4%, 0.6%); and diarrhea (3.0%, 2.3%).

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Janumet (Sitagliptin/metformin) 50/500 or 50/1000 mg tab 1 tab bid PO Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin INSULIN treatment Rapid-Acting | Short-Acting | Intermediate-Acting | Long-Acting | Combination | New Inhaled Insulin | Non-insulin subc

RAPID-ACTING: as Humalog & Novolog insulin

Onset: 10-30 min | Peak: 30-60 min | Duration: 3-5 h 2002)

(Medical Letter September

Humalog insulin analog is faster but shorter duration action than Human regular insulin. Use within 15 min before meals. Injection, solution, aspart, human:

NovoLog: 100 units/mL (10 mL vial) NovoLog [PenFill]: 100 units/mL (3 mL cartridge)

Injection, solution, lispro, human:

Humalog: 100 units/mL (1.5 mL cartridge, 3 mL disposable pen, 10 mL vial)

Injection, Apidra (insulin glulisine) given within 15 min premeal or within 20 min after starting a meal.

SHORT-ACTING: Regular insulin

Onset: 30-60 min | Peak: 1.5-2 h | Duration: 5-8 h

Injection, solution, regular, human:

Humulin R: 100 units/mL (10 mL vial)


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Novolin R: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial) Novolin R [PenFill]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

Injection, solution, regular, human, buffered :

* Velosulin BR [Discontinued]: 100 units/mL (10 mL vial)

Injection, solution, regular, purified pork:

Regular Iletin II: 100 units/mL (10 mL vial)

INTERMEDIATE-ACTING: NPH or Lente insulin

Onset: 1-2 h | Peak: 4-8 h | Duration: 10-20 h

Injection, suspension, lente, human [zinc]:


Humulin L, * Novolin L [Discontinued]: 100 units/mL (10 mL vial) Injection, suspension, lente, purified pork [zinc]: Lente Iletin II: 100 units/mL (10 mL vial) [Discontinued]

Injection, suspension, NPH, human [isophane]:


Humulin N: 100 units/mL (3 mL disposable pen, 10 mL vial) Novolin N: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial) Novolin N [PenFill]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

Injection, suspension, NPH, purified pork [isophane]:

NPH Iletin II: 100 units/mL (10 mL vial)

Injection, Levemir [insulin determir (rDNA origin)] subc once or twice daily

Onset of action: 23 h; Duration of action: 924 hr; Peak action: variable modest peak: 610 hr

LONG-ACTING: Ultralente insulin Injection, suspension, Ultralente, human [zinc]:


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Humulin U Ultralente: 100 units/mL (10 mL vial) Onset: 2-4 h | Peak: 8-20 h | Duration: 16-24 h

Injection, solution, glargine, human:

Lantus (Insulin glargine - rDNA origin) once a day injection, start 10 IU daily (about the same dose as NPH) 100 unit/mL (10 mL vial) Onset: 1-3 h | Peak: no peak | Duration: 20-24 h

Pramlintide (Amylin)

Adjunct to insulin for patients who fail to achieve glycemic control with insulin alone Inject subcutaneously before meals Dose: 15 g initially, titrate upward as necessary to 3060 g Reduce preprandial insulin by 50% initially

COMBINATION, INTERMEDIATE-ACTING: Injection, aspart protamine human suspension 70% and rapid-acting aspart human solution 30%

(NovoLog Mix 70/30): 100 units/mL (3 mL cartridge, 3 mL prefilled syringe)

Injection, lispro protamine human suspension 75% and rapid-acting lispro human solution 25%

(Humalog Mix 75/25): 100 units/mL (3 mL disposable pen, 10 mL vial)

Injection, NPH human insulin suspension 50% and short-acting regular human insulin solution 50%

(Humulin 50/50): 100 units/mL (10 mL vial)

Injection, NPH human insulin suspension 70% and short-acting regular human insulin solution 30%:

Humulin 70/30: 100 units/mL (3 mL disposable pen, 10 mL vial) Novolin 70/30: 100 units/mL (1.5 mL prefilled syringe, 10 mL vial) Novolin 70/30 [PenFill]: 100 units/mL (1.5 mL cartridge, 3 mL cartridge)

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NEW Insulin

Inhaled insulin (Exubera - Pfizer) - NEW 2006 ! Onset of action: 1530 min; Peak action: 1.52 hr; Duration of action: 68 hr Dose: 1 mg for pts 30-39.9kg, and then add 1 mg for every 20 kg in patient over 40 kg. Supply: 1-mg and 3-mg blister pakcs. The 1-mg pack is approximately equivalent to 3 units of subc regular insulin, 3-mg pck is about 8 units of subc regular insulin. Jan. 27, 2006 The first inhaled insulin (Exubera) was approved today by the US Food and Drug Administration (FDA) for the treatment of adult patients with type 1 and type 2 diabetes. An inhaled powder form of recombinant human insulin (rDNA), the drug and delivery system is the first new insulin formulation introduced since the discovery of insulin in the 1920s, according to the FDA. FDA recommends pulmonary function testing at the start of Exuber therapy, at 6 months, and every year thereafter. Exubera is used 10-15 min before meals for prandial insulin coverage only; patients still need subc injections of long-acting insulins for basal coverage. Exubera is contraindicated in patients with preexisting lung disease and in smokers.

Sulfonylureas (as Glipizide/Glucotrol, Glyburide/Micronase) | Biguanides (Metformin/Glucophage) Thiazolidinediones (Pioglitazone/Actos, Rosiglitazone/Avandia) | Meglitinide (Prandin/Repaglinide, Starlix/Nataglinide) a-Glucosidase inhibitors (Acarbose/Precose, Miglitol/Glyset) | GLP Analogues (Exenatide/Byetta, Pramlintide/Symlin Subc) DPP IV Inhibitors (Vildagliptin/Galvus, Sitagliptin/Januvia PO) | Insulin, etc Rx , New Inhaled Insulin (Exubera) Correlation of HgA1c to Average Blood Glucose

6% - 135 mg/dL | 7% - 170 mg/dL | 8% - 205 mg/dL | 9% - 240 mg/dL | 10% 275 mg/dL | 11% - 310 mg/dL | 12% - 345 mg/dL Each 1% above 6% add 35 mg/dl to the base 135 mg/dL.

2006 General Guidelines for Management of Patients Presenting with High Blood Sugars Diabetic Ketoacidosis
For blood glucose 300 - 500 mg/dl:
1. Give 10 units Regular or Novolog (Aspart) insulin + 10 units NPH insulin

subcutaneously. 2. Order the following STAT labs the day of the visit: " RBS, lytes, BUN, Cr, ketones (add appropriate lab studies if not done recently i.e. nonLloyd Institute Of Management &Technology Page 51

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fasting DM panel (HbA1c, urine Microalbumin, non-fasting HDL, LDL, ALT).


3. If DCC follow-up is desired, schedule same-day (SDD) appointment for the next working

day. 4. Start oral agent and give diabetes education packet. " Order on Health Connect or give prescription for One Touch Ultra glucose meter kit with extra strips (Sure Step, if elderly). " Please call DCC or patient may contact the Call Center to schedule for a meter instruction class (60-90 minutes) at DCC Imperial Bldg. B Suite 327, # 8-327-2440 (Imperial ext. 72440). **It is important that patient is told to bring his/her machine to the class. 5. Recheck blood sugar before patient is discharged home. Goal: blood sugar <300. 6. Review with patient the need to force fluids and eat on schedule. For blood glucose greater than 500 mg/dl (but glucose less than 700 mg/dL and serum CO2>20):
1. Give 15 units Regular or Novolog (Aspart) insulin + 10 units NPH insulin

2.
3.

4.

5.

subcutaneously. Order the following STAT labs on the day of the visit: RBS, lytes, BUN, Cr, ketones " Add appropriate lab studies if not done recently i.e.,non -fasting DM panel (HbAlc, urine microalbumin, and non-fasting HDL, LDL, ALT). Start IV hydration with 1 liter normal saline. Give 20 meq KCl p.o. if K+ is <3.5. " Blood sugar should be checked hourly. " Call DCC 8-327-2440 (Imperial ext. 72440) if assistance is needed. During after-hours, send the patient to ED for hydration and further treatment after initial insulin injection. If DCC follow-up is desired, schedule same-day (SDD) appointment for the next working day. Phone: 8-327-2440 (Imperial ext. 72440) or Fax a referral: 8-327-2402 (Imperial ext. 72402) Labs to be done before follow-up visit: stat FBS, ketones, and lytes (if abnormal on day of initial visit). Start oral agent or add insulin if indicated. " Give diabetes education packet and encourage pt. to attend MHE classes. " Order on Health Connect or give prescription for One Touch Ultra glucose meter kit and extra strips (Sure Step, if elderly). " Please call DCC or patient may contact the Call Center to schedule for a meter instruction class (60-90 minutes) at DCC Imperial Bldg. B, Suite 327, tie line 8-327-2440 (Imperial ext. 72440). **It is important that patient is told to bring his/her machine to the class. " Insulin instruction classes (60 minutes) can also be scheduled at DCC 8-327-2440 (Imperial ext. 72440). **Please provide patient with prescriptions for insulin and syringes before discharge. Include a separate written order that notes dose of insulin you want patient to be started

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on.
6. Recheck blood sugar before patient is discharged home. Goal: blood sugar <300.

7. Review with patient the need to force fluids and eat on schedule.

For blood glucose >700 mg/dl or C02 <20,

patients should be sent to Emergency Room Department after giving insulin and 20 meq KCL p.o if K+ is <3.5. If patient appears dehydrated, start one liter normal saline IV and transport by ambulance.

Conclusion

As per my patient counseling, diabetes is a common disease of middle aged group. It can be manifested by increase BP, increase glucose plasma level, glycosurea. It can be controlled completely taking proper precaution and medication. There are several effective medications in market (TRIAPRIDE, DIAPRIDE FORTE) for diabetes. It may be fatal if not treated or not to be taken proper precaution. Pharmacists in retail shop or well aware about diabetes and perform better counseling of patients.

REFERENCELloyd Institute Of Management &Technology Page 53

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Wikipedia Encyclopedia http://www.www.ndei.org Diabetes mellitus: a fundamental and clinical text. 2nd ed. Edited by Derek LeRoith, Simeon Taylor, Jerrold M. Olefsky Ellenberg & Rifkin's diabetes mellitus. 5th ed. Edited by Daniel Porte, Jr., Robert S. Sherwin. Stamford, CT, Appleton & Lange, c1997. 1423 p. Includes bibliographical references. Joslin, Elliott P. Joslin's diabetes mellitus. 13th ed. Edited by C. Ronald Kahn, Gordon C. Weir. Philadelphia, Lea & Febiger, 1994. 1068 p. Textbook of diabetes. 2nd ed. Edited by John C. Pickup and Gareth Williams. Oxford, Cambridge, MA, Blackwell Science, 1997. 2 v. American Diabetes Association complete guide to diabetes: the ultimate home diabetes reference. 2nd ed. Alexandria, VA, American Diabetes Association, c1999. 506 p. Beaser, Richard S., Joan V.C. Hill, and the Joslin Education Committee. The Joslin guide to diabetes: a program for managing your treatment. New York, Simon & Schuster, c1995. 351 p. Betschart, Jean, and Susan Thom. In control: a guide for teens with diabetes. Minneapolis, MN, Chronimed Pub., c1995. 116 p Saudek, Christopher D., Richard R. Rubin, and Cynthia S. Shump. The Johns Hopkins guide to diabetes: for today and tomorrow. Baltimore, MD, Johns Hopkins University Press, 1997. 422 p Medical Pharmacology author KD Tripathi.

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