1. Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD) Al Maarefa Colleges (KSA) & Zagazig University (EGY) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD) Al Maarefa Colleges (KSA) & Zagazig University (EGY) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit

2. At the end of this lecture, students should be able to: Define diabetes mellitus. Enumerate the types of diabetes mellitus. Describe type 1 diabetes mellitus. Describe type 2 diabetes mellitus. Compare type 1 to type 2 diabetes mellitus. Know insulin resistance and its results. Discuss the link between obesity and insulin resistance. Discuss Characteristic disturbances of diabetes mellitus. Know diagnosis of diabetes mellitus. Describe the complications of diabetes mellitus.

4. DIABETES MELLITUS  The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.  The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.

5. Types of DIABETES MELLITUS 1- Secondary Diabetes: (↑ anti-insulin hormones) Cushing’s syndrome (Cortisol excess). Acromegaly (Growth hormone excess). Pheochromocytoma (Catecholamine excess). Glucagonoma (Glucagon). 2- Primary Diabetes: Type I diabetes Type II diabetes Gestational diabetes

6. Type I diabetes Type II diabetes 10 % of cases of diabetes.90 % of cases of diabetes. Immune-mediated diabetes occurs in childhood, but it may occur at older age. Latent Autoimmune Diabetes in Adults (LADA) is a form of autoimmune type I diabetes. Age of onset from 35 years upwards, but it may occur at younger age. Maturity Onset Diabetes of Young (MODY) is a form of type II that occurs at age below 25 years. There is little or no insulin secretion, as manifested by low or undetectable levels of plasma C-peptide. Normal or even increased insulin secretion. Decrease sensitivity of target cells to insulin i.e. insulin resistance Destruction of β -cells due to: a) Auto immune antibodies against beta cells. b) Viruses (Coxsackie and Mumps) against beta cells. Insulin Resistance may be due to: a) Abdominal obesity is a big risk factor. b) Physical inactivity. c) Aging. d) Genetics.

13. Insulin resistance A condition in which muscle, fat, and liver cells do not respond properly to insulin and thus cannot easily uptake glucose from the bloodstream. Over time, insulin resistance can lead to pre- diabetes and type 2 diabetes as the beta cells fail to keep up with the body’s increased need for insulin.

14. The major contributors to insulin resistance & type II DM

15. Diabesity  The link between obesity and insulin resistance:  Obesity, especially excess fat around the waist, is a primary cause of insulin resistance.  Belly fat plays a part in developing chronic, or long- lasting, inflammation in the body that decreases insulin sensitivity.  Adipocytokines secreted by adipose tissue modulate response of target tissue to insulin: I.Resistin (promotes insulin resistance), increases in obesity. II.Adiponectin (increases insulin sensitivity), decreases in obesity.

21. 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. Untreated gestational diabetes can damage the health of the fetus or mother.

22. Characteristic disturbances of diabetes (Clinical results of insulin deficiency) 1)Hyperglycemia: * Rise of fasting blood glucose ≥ 126 mg %. * Rise of post prandial blood glucose ≥ 200 mg %. 2) Glucosuria: * If blood glucose level rises above renal threshold (=180 mg %) 3) Lipid disturbances : *  lipolysis to supply fatty acids for gluconeogenesis & energy production   free fatty acids  oxidation of fatty acids for energy production  formation of ketone bodies  Ketonaemia  ketoacidosis.

23. 4) Negative nitrogen balance:  Protein catabolism  loss of weight. Hypoprotienaemia  low resistance to infections. 5) Polyuria & Polydipsia. 6) Dehydration, Na + & k + Depletion. 7) Circulatory failure, coma & death if not treated. Characteristic disturbances of diabetes

26. Acute complications (Diabetic coma) 1)Diabetic ketoacidosis 2)Hypoglycemic coma

27. (Vascular complications)

29. Advanced glycation end products(AGEs)  AGEs are the addition of a carbohydrate to a protein without the involvement of an enzyme. The glycation process makes cells stiffer, less pliable and more subject to damage and premature aging.carbohydrateproteinenzyme  AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis.  AGEs have a range of pathological effects, such as:pathological effects 1)Increased vascular permeability & arterial stiffnessvascular permeabilityarterial stiffness 2)Inhibition of vascular dilation by interfering with nitric oxide.vascular dilationnitric oxide 3)Oxidizing LDL.Oxidizing LDL 4)Binding cells—including macrophage, endothelial, and mesangial—to induce the secretion of a variety of cytokines.macrophageendothelialmesangialcytokines 5)Enhanced oxidative stress.oxidative stress

30. Diagnosis and Classification of DM

32. Management of Diabetes Mellitus

34. The major components of the treatment of diabetes are: Management of type 2 DM Diet and Exercise A Oral hypoglycaemic therapy B Insulin Therapy C

35. Diabetes Management Algorithm