History

Diabetes Mellitus
The name diabetes mellitus means sweet urine.

Sushruta (600BC)
"Father of Surgery."

Ancient Hindu Physician noted polyuria of diabetes & sweet taste of diabetic urine

Diabetes Mellitus
Definition A metabolic disorder of multiple etiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both Associated with a risk of developing late diabetic complications including Microvascular (Retinopathy, Nephropathy) Macrovascular (Atherosclerosis) Neuropathy

Diabetes Mellitus
Chronic high blood [glucose]. 2 forms of diabetes mellitus: Type I: Juvenile/ Insulin dependent diabetes (IDDM). Type II: Adult onset/ Non-insulin dependent diabetes (NIDDM).

Comparison of Type I and Type II Diabetes Mellitus

Insert table 19.6

Type I Diabetes Mellitus

cells of the islets of Langerhans are destroyed by autoimmune attack which may be provoked by environmental agent. Glucose cannot enter the adipose cells. Fatty acids converted to ketone bodies, producing ketoacidosis. Increased blood glucagon Stimulates glycogenolysis in liver.

Consequences of Uncorrected Deficiency in Type I Diabetes Mellitus

Type II Diabetes Mellitus

Slow to develop. Genetic factors are significant. Occurs most often in people who are overweight. Decreased sensitivity to insulin or an insulin resistance.
Obesity.

Insert fig. 19.11

Insert fig. 19.12

Do not usually develop ketoacidosis. May have high blood insulin or normal insulin.

Who gets Type 2 Diabetes?

People who are overweight Have a parent or sibling with diabetes Are 40 years of age Have high blood pressure Are African America, Latino, or Native American Had diabetes during pregnancy Have the stress of an illness or injury Had a baby that weighed more than 9 pounds at birth.

Type 2 diabetes is often without symptoms in its early stages. Thats the reason there are 40% of people with Type 2 diabetes are unaware of their disease. When there are symptoms, they may occur gradually. If present, they usually are:

Feeling tired and weak Passing large volumes of urine, especially during the night (polyuria) Having frequent infections Having blurred eyesight Weight-loss Excessive hunger and thirst

Risks!
If left untreated this, Diabetes can cause many life threatening complications: Blindness Chronic Renal Failure= kidney failure Atherosclerosis= heart attacks and stroke Diabetic Neuropathy= numbness and pain to hands and feet Foot Ulcers Autonomic Neuropathy= diarrhea, rapid heart beat, and low blood pressure

Risks!
Coma or death may occur as a result in Diabetic Ketoacidosis (caused by infection) People who smoke are at much higher risk of heart attacks, stroke, infections, and problems with poor circulation

Classification of diabetes
Gestational Diabetes Mellitus (GDM) developing during some cases of pregnancy but usually disappears after pregnancy. Impaired glucose regulation/Impaired fasting glucose Other rare forms include maturity-onset diabetes of the young (MODY)
Weight Loss

Primary prevention
Primary prevention

Physical Activity

Stop Smoking

Physical Activity and Diabetes Prevention

Physical activity decreases insulin resistance and can aid in both preventing type 2 diabetes mellitus and managing the disease. Physical activity has an insulin-like effect -- it can help lower blood sugar levels. Epidemiological studies suggest that physical activity can reduce the risk of non-insulin-dependent diabetes by up to 50 percent.

Smoking Predisposes to Type 2 Diabetes

Studies shown correlation between smoking and the risk of developing type 2 diabetes.
The risk is dose-dependent:

The longer you smoke, the higher the risk

Triad of Treatment
Diet Medication
Oral hypoglycemics Insulins

Treatment in Diabetes
Change in lifestyle: Increase exercise: Increases the amount of membrane GLUT4 carriers in the skeletal muscle cells. Weight reduction. Increased fiber in diet. Reduce saturated fat.

Exercise

Diabetic Profile Tests

Fasting Plasma Glucose Test
(FPG) - (cheap, fast) *fasting B.G.L. 100-125 mg/dl signals prediabetes *>140 mg/dl signals diabetes

Oral GlucoseTolerance Test (OGTT)

*tested for 2 hrs after glucose- rich drink *140-199 mg/dl signals prediabetes *>200 mg/dl signals diabetes

Glycated Hemoglobin tests (GHb) HbA1C Urine Glucose & Microalbumin

Diabetic Profile Tests

Oral Glucose Tolerance Test

Measurement of the ability of cells to secrete insulin. Ability of insulin to lower blood glucose. Normal persons rise in blood glucose after drinking glucose solution is reversed to normal in 2 hrs.

Insert fig. 19.8

Importance of OGTT
Asymptomatic patients with normal blood glucose may show high PP blood glucose Normal Fasting 140 mg/dl PP 200 mg/dl Diabetic patients - Fasting 140 mg/dl PP 200 mg/dl

Hyperglycemic Complications
IDDM

Decreased insulin & fluids

Diabetic Ketoacidosis

Diabetic Coma (Unconciousness)

Hyperglycemic Complications
NIDDM

Additional Tests done in Diabetic Ketoacidosis

Some insulin present

No Ketoacidosis

Polyuria due to increased glucose

Hyperosmolar Nonketonic Coma

Hypoglycemia

Hypoglycemia Etiology
1. Over treatment with oral hypoglycemic drugs or insulin 2. Insufficient food intake 3. Too much exercise with insufficient food intake

Insert fig. 19.13

Hypoglycemia Symptoms
Decrease in glucose Hypoglycemia

Rebound or Somogyi Effect

Hyperglycemia that follows a severe hypoglycemia

Stimulates release of epinephrine Nausea Weakness Lightheadedness Rapid Pulse Sweating Epigastric discomfort

Fasting Hypoglycemia
Spontaneous hypoglycemia with abnormally low levels of glucose within 12 hrs of beginning of fasting

Fasting Hypoglycemia Etiology

1. Drugs like propranolol, salicylates, disopyramide etc. 2. Oral hypoglycemic agents 3. Ethanol (inhibits gluconeogenesis) 4. Hepatic failure (decrease glycogen) 5. Deficiency of thyroxine, glucagon, glucocorticoids, GH, ACTH. 6. Islet cell tumor 7. Septicemia

Reactive Hypoglycemia Etiology

Reactive Hypoglycemia
Postprandial autonomic symptoms with low glucose levels after 1 to 3 hrs after eating.
1. Partial gastrectomy (rapid passage of glucose in blood stream and excessive secretion of insulin which utilizes it) 2. Fructose intolerance (accumulation of fructose 1 phosphate inhibits glucose synthesis)

Diabetes Self-testing Dr. Elliott Joslin, American diabetologist urine test for glucose.

Diabetes Self-testing Uristix dip-and-read enzyme based urine strips

Diabetes Self-testing
Glucometers home blood glucose monitoring (HBGM) by people with diabetes mellitus or with proneness to hypoglycemia

Preclinical Testing
American Diabetes Association (ADA) recommends first-degree relatives of IDDM patients & offsprings of NIDDM patients following tests 1. ICA (Islet Cell Antibodies) 2. IAA (Insulin Antibodies) 3. Insulin Secretion

Insulin Test
1. To determine Fasting Hypoglycemia 2. For differentiating patients required to be treated with insulin from those which can be controlled with diet.

Proinsulin & C peptide Test

To diagnose patients with benign or malignant beta cell tumor of pancreas

Advantage of C-peptide Over Insulin

1. Since hepatic metabolism is negligible C-peptide is better indicator over insulin 2. C-peptide do not cross react with insulin Ab which interfere in insulin immunoassays 3. It does not measure exogenous insulin