Diabetes mellitus Lecture Outline I. Diagnosis II. Epidemiology III. Causes of diabetes IV. Health Problems and Diabetes V. Treating Diabetes VI. Physical activity and diabetes 1
Diabetes Disorder characterized by a relative lack or insensitivity to hormone insulin. Diabetics show high blood sugar levels and presence of sugar in the urine Develops when insulin production or insulin use is inadequate Most cases are classified as type 1(I) or type 2 (II) Two other types: gestational and secondary (due to genetic defects, infections, diseases of exocrine pancreas, drug induced etc.) Prevalence increases with aging; affects 25% of adults over 85 years of age Diagnosis of Diabetes Impaired fasting glucose: plasma glucose > 125mg.100ml -1 (>7mmol.L -1 ) following an 8 h fast. Glucose tolerance test (GTT): Oral: drink a solution in which 75 g of anhydrous glucose is dissolved in water. 2 hours later: plasma glucose >200mg.100ml -1 (>11.1mmol.L -1 ) Intravenous: catheter placed in both arms. Glucose solution injected into one arm and blood samples drawn from the other arm over a course of 3 hr. Allows to develop a curve of glucose and insulin responses. Pre-Diabetes : American Diabetes Association (1997): Fasting glucose: 110-125mg.100ml -1 (6.1-6.9mmol.L -1 ) American Diabetes Association (2003): Fasting glucose: 100-125mg.100ml -1 (5.6-6.9mmol.L -1 ) GTT: 140-200mg.100ml -1 (7.8-11mmol.L -1 ) 2
Diagnosis of Diabetes Venous plasma glucose (mg/dl) Time after oral glucose (min) Epidemiology of type 2 diabetes Worldwide: - in 2002: estimated170-200 million cases; - prediction, by 2020: 300 million (WHO) Ireland: - estimated 200,000 diabetics, and a further 200,000 who have diabetes but are unaware that they have the condition. - a further 250,000 people have impaired glucose tolerance ("prediabetes ) of which 50% will develop diabetes in the next 5 years if lifestyle changes are not made. 3
Epidemiology of type 2 diabetes Wild et al., Diabetes care 2004 Type 1 Diabetes Mellitus Insulin dependent diabetes mellitus (IDDM) Onset occurs most often during childhood or young adulthood Requires daily injections of insulin (due to ß-cell dysfunction) administered subcutaneously: long, intermediate or short periods of time Includes 10% to 15% of all individuals with diabetes 4
Type 2 Diabetes Mellitus Non-insulin dependent diabetes mellitus (NIDDM) Onset occurs most often gradually during adulthood* RISK FACTORS: Family history, lack of exercise, obesity, ethnic background, age, history of gestational diabetes Causes: - Heredity Excessive hepatic glucose production Peripheral insulin resistance (insensitivity) and Defective ß-cell secretory function. - Obesity Beta-cells become less responsive to increased blood glucose Target cells undergo reduction in active insulin receptors Includes 85% to 90% of all individuals with diabetes Actions of Insulin Figure 21.5 G&S 3rd Ed 5
Glucose Regulation Via Insulin Via Glucagon Plasma glucose Plasma glucose Negative feedback Beta cells in pancreas Insulin secretion Negative feedback Alpha cells in pancreas Glucagon secretion Most tissues Liver and muscle Liver Glucose uptake into cells Glycogen synthesis Glycogenolysis Gluconeogenesis Liver Adipose tissue Gluconeogenesis Lipolysis Glycogenolysis Plasma fatty acids Plasma glucose Plasma glucose Glucose spared (a) (b) Figure 21.7 G&S 3rd Ed Health Problems and Diabetes Macrovascular: Coronary artery and peripheral vascular disease Capillary abnormalities: blood platelets more adhesive or stickier: greater risk of thrombosis (clotting) Neuropathy (nerve damage): through deterioration of myelin Hypertension Gangrene Ulceration of the skin Microvascular: Renal disorders Eye disorders: blindness, cataracts 6
Treating Diabetes Type II: Controlled by diet alone or in combination with antidiabetic drugs Oral hypoglicemic agents (sulfonylureas): stimulate insulin secretion Metformin: inhibit excessive hepatic glucose production Troglitazone: reduces insulin resistance Sometimes injections of insulin Type I: Individualized insulin administration and monitoring Well-balanced diet #Regular exercise and physical training GLUT-4 (glucose transporter) to cellular membrane During exercise: Contractions regulated by AMPK pathway (effect lasts after 3-6 h post-exercise) PI3K pathway (subsequent 42 h of recovery) So, plasma insulin levels decrease (by inhibition of ß-cell activity via exercise-induced catecholamine release); so, need for insulin decreases and insulin sensitivity of muscle cell increases. Figure 20.19 M,K&K 3rd Ed 7
Physical Activity and Diabetes People with type I diabetes may or may not improve their glycemic control with exercise, but exercise will help lower their risk for coronary artery disease (reductions in lipid profile, BP, abdominal fat) Preventing Hypoglycemia during exercise: Differences in insulin release (physiological versus injected) Site of injection Pre-exercise: If blood glucose < 100mg.100ml -1 : delay exercise, 10-15 g of CHO should be consumed Post-exercise: Blood glucose <70mg.100ml -1 Ingestion of 15g of CHO, wait 10-15 min, if necessary another 15g CHO If unconscious: injection of glucagon Physical Activity and Diabetes Preventing Hyperglycemia during exercise: If blood glucose > 250mg.100ml -1 : delay exercise If insulin not adequate elevated blood glucose and ketosis. Ketone conc, can rise 30 times above normal: extreme acidosis and diabetic coma. Attention to foot care (especially type I diabetes) due to decreased sensation and peripheral blood flow in the feet. Exercise improves insulin sensitivity (and thus, decreases insulin resistance) for glucose transport in skeletal muscle and adipose tissue from 1) translocation of GLUT-4 from the endoplasmic reticulum to the cell surface 2) increase in the total quantity of GLUT-4 8
Physical Activity and Diabetes: Exercise Prescription Complete CVS evaluation before program commences Exercise mode dependent on complications (I.e. diabetics with peripheral neuropathy jogging may cause trauma in legs, more appropriate swimming, cycling) Aerobic training: Intensity: 60-80% HR max, 50-80% VO 2 max Frequency: 3-5 times/wk for 30 to 60 min. Resistance training: 8-10 exercises; minimum one set of 10-15 reps Frequency: 2 times/wk A combination of aerobic and resistance exercise program improves markers of insulin resistance more than endurance training alone. Timing: Time of the day most convenient for patient Avoid exercise late in the evening (risk of hypoglycemia when sleeping) 9