DIABETES MELLITUS

DIABETES MELLITUS
Diabetes mellitus is a chronic disease due primarily to a disorder of carbohydrate metabolism, cause of which is deficiency or diminished effectiveness of insulin, resulting in hyperglycemia and glycosuria. May also cause secondary changes in metabolism of proteins, and lipids leading to grave consequences.

DIABETES - STAGES
There are 4 stages in diabetes:
Pre-diabetics Suspected diabetes Chemical/Latent diabetes Overt diabetes

DIABETES - TYPES
There are three major forms of diabetes: Type I Diabetes (IDDM) (Juvenile onset)
Type II Diabetes (NIDDM) (Maturity onset)

Gestational Diabetes

DIABETES MELLITUS FACTORS Heredity Obesity Diet Insulin antagonism

PATHOPHYSIOLOGY
Pancreas is composed of cells scattered throughout called the islets of Langerhans Two types of cells are important to glucose control Alpha cells- produce glucagon
Hormone that acts opposite of insulin Causes release of glucose from cell storage

Beta cells- produce insulin

Allows body cells to use and store carbohydrate, fat, and protien

INSULIN
Insulin allows glucose to move into cells to make energy Liver is first major organ to be reached
Promotes production and storage of glycogen (glycogenisis) Inhibits glycogen breakdown into glucose (glycogenolysis) Increases protein and lipid synthesis Inhibits tissue breakdown by inhibiting liver glycogenolysis (ketogenesis- converts fats to acids) & gluconeogenisis (conversion of proteins to glucose) In muscle, promotes protein and glycogen synthesis In fat cells, promotes triglyceride storage

INSULIN
Pancreas secretes 40-50 units of insulin daily in two steps:
Secreted at low levels during fasting ( basal insulin secretion Increased levels after eating (PP) An early burst of insulin occurs within 10 minutes of eating Then proceeds with increasing release as long as hyperglycemia is present

GLUCOSE HOMEOSTASIS
Glucose is main fuel for CNS Brain cannot make or store, therefore needs continuous supply Fatty acids can be used when glucose is not available ( triglycerides) Need 68-105 mg/dL to support brain Decreased levels of glucose, insulin release is stopped with glucagon released

GLUCOSE
Glucagon causes release of glucose from liver
Liver glucose is made thru glycogenolysis (glucogen to glucose) & Gluconeogenesis

When liver glucose is not available, lypolysis occures ( breakdown of fat) OR Proteinlysis (breakdown of amino acids)

ABSENCE OF INSULIN
Insulin needed to move glucose into cells. Without insulin, body enters a state of breaking down fats and proteins. Glucose levels increase (hyperglycemia).

DIABETES - TYPE I
It results from primary beta cell destruction leading to absolute insulin deficiency. Also caused by genetic defects of beta cell; genetic defects in insulin action; other endocrine and exocrine dysfunctions; drug induced; other genetic syndromes

DIABETES TYPE I

Frequency: less Commences usually before 15 yrs of age. Frequency: Males > than Females. Onset: rapid and abrupt Speedy Progression to Keto-acidosis and coma Usually patients are thin and underweight Deficient Insulin: At first Juvenile diabetics produce more insulin than normal, but the beta-cells soon become exhausted and patient becomes "overt" diabetics and practically no insulin . Plasma insulin- It is almost absent. No insulin response is shown to glucose load. Insulin therapy-is necessary for control of these cases.

DIABETES TYPE II
Frequency-more common. Occurs in middle aged individuals. More common in women. Onset is insidious Usually mild. Ketoacidosis is rare. Associated with obesity in 2/3 of cases. Usually detected during routine check-up of urine. Beta cells respond normally. Relative insulin deficiency may be due to insulin antagonism. Plasma levels of insulin may be normal or raised. Oral hypoglycemic agents and diet control are useful in treatment.

GESTATIONAL DIABETES
Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.

GDM SYMPTOMS
Glycosuria. Elevated blood glucose levels. Usually appears between 24-28 weeks gestation. Degree of hyperglycemia is not as severe as in other types of diabetes.

SECONDARY DIABETES
This condition is observed when diabetes occurs secondary to some diseases. Pancreatic diabetes:
Pancreatitis Haemochromatosis Malignancy of Pancreas.

Abnormal concentrations of antagonistic hormones

Hyperthyroidism Hypercorticism: like Cushings syndrome Hyperpituitarism: like acromegaly Increased glucagon activity.

Iatrogenic
In genetically susceptible cases, may be precipitated by therapy like corticosteroids, thiazide diuretics.

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

Polyuria Polydypsia Polyphagia Weakness and fatigue Diabetic Ketoacidosis Hypercholesterolemia leading to atherosclerosis Weight loss Hemoconcentration- related to dehydration Hypovolemia- decreased blood volume Hyperviscosity thick concentrated blood Hypoperfusion- decreased circulation Hypokalemia and Hyponatremia Kussmaul respirations

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

Polyuria:
Frequent and excessive urination Osmotic diuresis caused by excess glucose in urine Water loss can be severe along with sodium, chloride, and potassium

Polydipsia:
Excessive thirst associated with dehyration

Polyphagia:
Cells do not receive glucose leading to starvation which triggers excessive eating

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

Weakness and fatigue
Due to lack of glucose available for ATP formation.

Weight loss
Catabolism of lipids and proteins as a part of gluconeogenesis

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

Diabetic Ketoacidosis
DKA results in altered lipid metabolism. increased concentrations of total lipids, cholesterol, triglycerides, and free fatty acids. free fatty acids are shunted into ketone body formation due to lack of insulin; the rate of formation exceeds the capacity for their peripheral utilization and renal excretion leading to accumulation of ketoacids, and therefore metabolic acidosis.

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

Hypercholesterolemia & Atherosclerosis
Abnormal lipid metabolism leading to FFA and cholesterol biosynthesis. Cholesterol deposition - lead pipe arteries

CLINICAL FEATURES AND BIOCHEMICAL CORRELATIONS

Kussmaul respirations:
Excess acids cause increased H+ and CO2 levels Stimulate brain to increase rate and depth of respirations to excrete acid and carbon dioxide Acetone is exhaled thus breath has fruity odor Ultimately, pH will drop

Hypokalemia and Hyponatremia

Lack of insulin causes depletion of potassium and sodium

CHRONIC COMPLICATIONS
Blood vessels changes
Macrovascular:
Coronary heart disease, cerebrovascular accidents; & peripheral vascular disease Major risk factor for CAD, MI

Microvascular:
Nephropathy (kidney dysfunction); neruopathy (nerve dysfunction); & retinopathy (vision problems) Blindness is 25 times more common Microaneurysms Neovascularization- new blood vessels but thin, fragile and bleed easily Male erectile dysfunction (ED)

DIABETIC RETINOPATHY
Diabetes results in changes in veins, arteries and capillaries in the body. Risk of developing diabetic retinopathy: damage occurs to the fragile blood vessels inside the retina. Could develop cataracts (clouding of the naturally clear lens in the eye). May develop glaucoma (a disease of the optic nerve). 2 Forms Non proliferative Diabetic Retinopathy (NPDR) and Proliferative Diabetic Retinopathy (PDR).

NPDR
Early stage diabetic retinopathy Hard exudates on the central retina (macula). Microaneurysms (small bulges in blood vessels of the retina that often leak fluid). Retinal hemorrhages (tiny spots of blood that leak into the retina). Macular edema (swelling/thickening of macula). Macular ischemia (closing of small blood vessels/capillaries).

Retina showing NPDR

PDR
Later stage diabetic retinopathy Vitreous hemorrhage (new, abnormal blood vessels bleed into vitreous gel in center of eye, preventing light rays from reaching the retina). Traction retinal detachment (new, abnormal blood vessels begin to shrink and tug on retina; may cause retina to detach). Neovascular glaucoma (neovascularization occurs in the iris, causing pressure to build up in the eye, damaging the optic nerve).

Retina showing PDR

DIABETIC NEPHROPATHY
Diabetic nephropathy (nephropatia diabetica), also known as KimmelstielWilson syndrome and intercapillary glomerulonephritis. It is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. Characterized by nodular glomerulosclerosis.

DIABETIC NEPHROPATHY
Stage 1: Hyperfiltration, or an increase in glomerular filtration rate (GFR) occurs. Kidneys increase in size. Stage 2: Glomeruli begin to show damage and microalbuminurea occurs. Stage 3: Albumin excretion rate (AER) exceeds 200 micrograms/minute, and blood levels of creatinine and urea-nitrogen rise. Blood pressure may rise during this stage.

DIABETIC NEPHROPATHY
Stage 4: GFR decreases to less than 75 ml/min, large amounts of protein pass into the urine, and high blood pressure almost always occurs. Levels of creatinine and urea-nitrogen in the blood rise further. Stage 5: Kidney failure, or end stage renal disease (ESRD). GFR is less than 10 ml/min. The average length of time to progress from Stage 1 to Stage 4 kidney disease is 17 years for a person with type 1 diabetes. The average length of time to progress to Stage 5, kidney failure, is 23 years.

HYPERGLYCEMICHYPEROSMOLAR-NONKETOTIC SYNDROME AND COMA

Increased blood osmolarity caused by hyperglycemia Absence of ketosis and higher blood glucose levels & blood osmolarity (>800mg/dL) (44.5 mmol/L) Other manifestations are more severe

HHNS
MI, sepsis, pancreatitis, stroke, some drugs may cause HHNS Clients may have seizures or reversible paralysis Related to residual insulin secretion:
client secretes just enough insulin to prevent ketoacidosis, but not hyperglycemia Profound diuresis with e-lyte imbalance Decreased kidney perfusion leads to decreased urine output leading to decreased glucose in urine

DIABETIC NEUROPATHY AND DIABETIC FOOT

Neuropathy
Sensory Motor autonomic

Regulates sweating and perfusion to the limb Loss of autonomic control inhibits thermoregulatory function and sweating Result is dry, scaly and stiff skin that is prone to cracking and allows a portal of entry for bacteria

DIABETIC FOOT
Loss of protective sensation Starts distally and migrates proximally in stocking distribution Large fibre loss light touch and proprioception Small fibre loss pain and temperature Usually a combination of the two. Mild form of diabetic foot Charcot foot

DIABETIC FOOT
Mostly affects forefoot ulceration
Intrinsic muscle wasting claw toes Equinous contracture

Two mechanisms of Ulceration

Unacceptable stress few times
rock in shoe, glass, burn

Acceptable or moderate stress repeatedly

Improper shoe ware deformity

DIABETIC FOOT
Wagners Classification 1. Intact skin (impending ulcer) 2. Superficial 3. Deep to tendon bone or ligament 4. Osteomyelitis (Bone marrow inflammation) 5. Gangrene of toes or forefoot 6. Gangrene of entire foot

METABOLIC CHANGES IN DIABETES MELLITUS

LAB DIAGNOSTICS
Urine tests:
Ketones Renal function Glucose

Blood tests:
Fasting blood glucose test Oral glucose tolerance test Glycosylated hemoglobin assays Glycosylated serum proteins and albumin

URINE TESTS
Ketones:
Waste products of fat metabolism Presence in urine may indicate pending ketoacidosis

Renal function:
Urine protein without renal symptoms may indicate microvascular changes Albumin at 30-3000 mg/hr indicates too much protein in urine (microalbuminemia) Creatinine clearance tests

Glucose:
Blood glucose can be measured indirectly through urine

BLOOD TESTS
Fasting blood glucose:
Obtain blood thru venipuncture Fast for 8 hours Draw before Rx given; >126mg/dL X 2

Oral glucose tolerance:

Most sensitive test, but not routinely used Drinks beverage with 75 g of glucose; blood samples are drawn at 30 min intervals for 2 hours. >200 mg/dL at 120 minutes

BLOOD TESTS
Glycosylated hemoglobin assays:
Blood glucose attaches to hemoglobin Higher the glucose over time, > glycosyolated hemoglobin Good indicator of average blood glucose levels (HbA1c) Average glucose over last 120 days-life span of RBCs

Glycosylated serum proteins and albumim:

Like hemoglobin, serum proteins and albumin become satuated with glucose over time Turnover rate for proteins and albumin is 14 days, therefore assesses glucose over shorter period of time

DIABETES MANAGEMENT MEALS

MUST BE INDIVIDUALIZED NO SUCH THING AS DIABETIC DIET PORTION CONTROL IS THE KEY Goals include:
Keep BS and HgbA1c normal Optimal lipid levels Optimal BP Ensure adequate calories Preventing complications Improve overall health Facilitate healthy eating habits Meet nutritional and psychological needs Provide self management education May help to facilitate moderate weight loss if at risk for complications of obesity

MEALS
Day to day consistency in timing and amount helps control blood glucose Protein, carbohydrates, and fats must be consumed in appropriate amounts
Protein- 15-20% of total daily calories in clients with normal renal function (reduce to9 10% in renal dysfunction) Fat- <10% saturated fats; up to 10% in polyunsaturated fats Carbohydrates- emphasis in on total amount of CHO, not source

MEALS
High fiber improve carbohydrate metabolism and lower cholesterol (20-35 g of fiber per day) Increase fluid intake with fiber Nonnutritive sweeteners:
Saccharin Aspartame Acesulfame K Sucralose

MEALS
Fat replacers:
< 5 g of CHO per meal or < 20 calories Limit to 3 servings per day

Excess calories from any source are stored as adipose tissue and the storage capacity is unlimited

MEALS
Alcohol:
Moderate use if ok if diabetes is contolled; at risk for hypoglycemia so ingest with meals

Exchange system: no one size fits all

Based on 3 food groups Individualized for each meal

CHO counting
Focus on total CHO amounts CHO controls blood glucose levels 1 unit of rapid-acting insulin for each 15 g of CHO

Special considerations
Type I- spread CHO over 3 meals; avoid gaining weight Type II- reduce calories eaten and increase calories expended; 3 meals with snacks

MEDICATIONS
All medications must be used along with diet, exercise and stress management Two types to control diabetes:
Antidiabetic agents Insulin

MEDICATIONS
Oral therapy: prescribed after dietary control has been proven insufficient or if the client is highly symptomatic Classifications:
Sulfonylureas Meglitnide analogs Biguanides Alpha-glucosidse inhibitors Thiazolidinedione antidiabetic agents

MEDICATIONS: INSULIN
Insulin therapy is needed for Type I and many Type II diabetics Many types of insulin Dose varies but between 0.5-1 unit/kg/day Safety is issue for elderly patients, vision, mobility, coordination, and memory deficits

INSULIN
Types of insulin:
Obtained for animal sources such as beef or pork pancreas, combined, synthetic human and semisynthetic. There are differences in strength and onset of action between human and animal insulins Human is more rapid acting, shorter peak action, and shorter duration Human insulin is preferred during pregnancy or with clients with allergies or resistance to animal sources

INSULIN
Protocols:
Single daily: Two-dose: 2/3 before breakfast; 1/3 in evening Three-dose: breakfast, evening, bedtime Four-dose: before meals, bedtime

INSULIN
New technologies:
Insulin pumps: Inject continuous basal doses of insulin with increased doses at meals. Implanted insulin pumps: implanted into peritoneal cavity where blood supply absorbs insulin. Needleless devices: ultrathin liquid is forced under the skin with high pressure. Pen-type injectors: more precise smaller doses, easy to carry and use. Inhaled insulin: under development; pellet that is vaporized in an inhaler (like spiriva).

Photograph reproduced with permission of manufacturer.

SUMMARY
There is nothing inevitable about the complications of diabetes. However, the evidence is overwhelming that good control does count. Morbidity and mortality can be reduced.

SUMMARY
Insulin administration should mimic nature Natures way is basal insulin 24 hrs. a day. Insulin glargine or detemir can supply the basal with one injection per day.

SUMMARY
Assessment tools include Self Monitoring of Blood Glucose and HbA1C. Targets should be established for each of these for each patients within the national guidelines. When targets are not reached the help of a specialist should be sought.

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