Diabetes Mellitus

1. Diabetes Mellitus MaramAbdaljaleel, M.D University of Jordan, School of Medicine

2. Pancreas

3. The endocrine pancreas consists of the islets of Langerhans, which contain four major cell types—beta, alpha, delta, and PP (pancreatic polypeptide) cells. • beta cell insulin, • alpha cell  glucagon (raises glucose levels through its glycogenolytic activity in the liver) • Delta cells somatostatin (suppresses both insulin and glucagon release) • PP cells pancreatic polypeptide(secretion of gastric and intestinal enzymes and inhibition of intestinal motility). • The most important disease of the endocrine pancreas is diabetes mellitus, caused by deficient production or action of insulin.

4. Diabetes Mellitus: • Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia. • In the United States, diabetes is the leading cause of end-stage renal disease, adult-onset blindness, and nontraumatic lower-extremity amputations resulting from atherosclerosis of arteries.

5. Diagnosis • Blood glucose levels normally are maintained in a very narrow range, usually 70 to 120 mg/dL. • According to the American Diabetes Association (ADA) and the World Health Organization (WHO), diagnostic criteria for diabetes include the following: 1. A fasting plasma glucose > 126 mg/dL, and/or 2. A random plasma glucose >200 mg/dL (in a patient with classic hyperglycemic signs), and/or 3. A 2-hour plasma glucose > 200 mg/dL during an oral glucose tolerance test with a loading dose of 75 gm, and/or 4. A glycated hemoglobin (HbA1C) level > 6.5%

6. All tests, except the random blood glucose test in a patient with classic hyperglycemic signs, need to be repeated and confirmed on a separate day.

7. Impaired glucose tolerance (prediabetes) is defined as: 1. A fasting plasma glucose between 100 and 125 mg/dL (“impaired fasting glucose”), and/or 2. A 2-hour plasma glucose between 140 and 199 mg/dLduring an oral glucose tolerance test, and/or 3. HbA1C level between 5.7% and 6.4%

8. Pre- diabetics: • ¼ of patients with impairedglucose tolerance  diabetes in 5 years • prediabetes have an elevated risk of cardiovascular disease.

9. Simplified Classification of Diabetes: 1. Type 1 Diabetes: Beta cell destruction, usually leading to absolute insulin deficiency 2. Type 2 Diabetes: Combination of insulin resistance and beta cell dysfunction 3. Genetic Defects of Beta Cell Function: Maturity-onset diabetes of the young (MODY)& Insulin gene mutations 4. Genetic Defects in Insulin Action: Insulin receptor mutations 5. Exocrine Pancreatic Defects: Chronic pancreatitis, Pancreatectomy, Cystic fibrosis, Hemochromatosis 6. Endocrinopathies: acromegaly, Cushing syndrome, Hyperthyroidism,Pheochromocytoma 7. Infections: CMV, Coxsackievirus B, Congenital rubella 8. Drugs; Glucocorticoids & Thyroid hormone, β-Adrenergic agonists 9. Gestational Diabetes: Diabetes associated with pregnancy

10. TYPE 1 Diabetes millitus • 5-10% of all cases • autoimmune disease destructing pancreatic B-cells with absolute deficiency of insulin • childhood (<20 yr), becomes manifest at puberty • most patients depend on exogenous insulin for survival; without insulin they develop serious metabolic complications . • The classic manifestations of the disease occur late in its course, after 90% of the beta cells have been destroyed.

11. Type 2 diabetes millitus • 90-95 % of cases • caused by a combination of peripheral resistance to insulin action and an inadequate secretory response by the pancreatic β cells (“relative insulin deficiency”). • Although classically considered “adult-onset,” the prevalence of type 2 diabetes in children and adolescents is increasing at an alarming pace due to the increasing rates of obesity in these age groups.

12. Type 1 diabetes mellitus • The onset of the diseases is marked by polyuria, polydipsia, polyphagia. • Acute complications of type 1 diabetesdue to Deviations from normal diet, unusual physical activity, infection, or stress may predispose to diabetic ketoacidosis

13. Diabetic Ketoacidosis • type 1 diabetes, • The plasma glucose usually is in the range of 500 to 700 mg/dL • hyperglycemia causes an osmotic diuresis , dehydration andactivation of the ketogenicmachinery (activation of hormone-sensitive lipase) excessive breakdown of adipose stores increased FFAs oxidized by the liver to produce ketones leading to ketonemia and ketonuria. • If the urinary excretion of ketones is compromised by dehydration, the accumulating ketones decrease blood pH, resulting in metabolic acidosis.

14. Type 2 diabetes mellitus • Also may manifest with polyuria and polydipsia, • obese patients • In some cases, medical attention is sought due to unexplained weakness . - Most frequently, however, the diagnosis is made after routine blood or urine testing in asymptomatic persons.

15. In the decompensated state, patients develop hyperosmolar nonketotic coma. This syndrome is due to severe dehydration resulting from sustained osmotic diuresis and urinary fluid loss - The affected person is an elderly diabetic who is disabled by stroke or infection and unable to maintain adequate water intake. • The absence of ketoacidosis and its symptoms (nausea, vomiting, fruity smelling breath, abdominal pain, confusion, respiratory difficulties) delays recognition of the seriousness of the situation until the onset of severe dehydration and coma.

16. Complications of Diabetes I. MacrovascularDisease mainly accelerated atherosclerosis and complications including: a- Myocardial infarction( MI) • caused by Coronary artery atherosclerosis and is considered the most common cause of death in diabetics. - Diabetics have 2-4X greaterincidence of CAD, and 4Xhigher risk of death from CV complications, than nondiabetics. b- Gangrene of the lower extremities, is 100 times more common in persons with diabetes than in the general population

17. II. Diabetic Nephropathy: • Renal failure is second to MI as a cause of death from this disease. • is a leading cause of end-stage renal disease in the United States • The earliest manifestation of diabetic nephropathy is the appearance of small amounts of albumin in the urine (>30 but <300 mg/day) microalbuminuria • By 20 years after diagnosis, >75% of individuals with type 1 DM and 20% of type 2 DM with overt nephropathy will develop end-stage renal disease, necessitating dialysis or renal transplantation

18. III. Ocular Complications: • Diabetes is the 4th leading cause of acquired blindness in US. • 60%-80% of patients develop diabetic retinopathy (15-20 yrs after dx). • Presented as: • diabetic retinopathy: neovascularization is attributable to hypoxia-induced overexpression of VEGF in the retina. • glaucoma • cataract formation

19. IV. Diabetic Neuropathy. • distal symmetric polyneuropathy: - of the lower extremities +/- upper extremities “gloveand stocking”. • autonomic neuropathy, which produces disturbances in bowel and bladder function • diabetic mononeuropathy: - manifest as sudden footdrop, wristdrop, or isolated cranial nerve palsies.

20. V. increased susceptibility to infections: • skin, tuberculosis, pneumonia, and pyelonephritis. • Infections cause 5% of diabetes related deaths. • In an individual with diabetic neuropathy, a trivial infection in a toe may be the first event in a long succession of complications (gangrene, bacteremia, pneumonia) that may ultimately lead to death.

21. TREATMENT: • type 1 diabetesinsulinreplacement therapy is the mainstay of treatment, • type 2 diabetes • Dietary restrictions and exercise (that improves insulin sensitivity) are the "first line of defense" • Most patients will eventually require therapeutic intervention achieved by administration of a number of agents that lower glucose levels

22. HbA1C • Used to assess the glycemic control by measuring the percentage of glycosylated hemoglobin(HbA1C). • measures glycemic control over long periods of time (2 to 3 months) and is relatively unaffected by day-to-day Variations.

23. In summery:

25. Thank you