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  1. 1. Complications of Diabetes
  2. 2. What is Diabetes Mellitus? <ul><li>Diabainein in greek refers - to pass through </li></ul><ul><li>Mel refers to- honey </li></ul><ul><li>Diabetes - “sweet urine” </li></ul><ul><li>Chronic metabolic disorder characterized- persistent hyperglycemia, altered metabolism of lipids, carbohydrates and proteins. </li></ul>
  3. 3. Diagnostic Criteria American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10 FPG 2-h PPG (OGTT) 126 60 80 100 120 140 160 180 200 Plasma glucose (mg/dL) Normal Diabetes Mellitus 240 220 Diabetes Mellitus Normal IGT IGT 8
  4. 4. Etiological Classification <ul><li>I. Type 1 diabetes - previously known as juvenile diabetes </li></ul><ul><ul><li>insulin-dependent diabetes mellitus (IDDM) </li></ul></ul><ul><li>II. Type 2 diabetes - previously known as adult-onset diabetes </li></ul><ul><ul><li>non-insulin-dependent diabetes mellitus (NIDDM) </li></ul></ul><ul><li>III. Gestational diabetes mellitus (GDM) </li></ul>American Diabetes Association
  5. 5. Type- I Diabetes Mellitus <ul><li>T cell-mediated destruction of pancreatic ß-cells </li></ul><ul><li>Rapid onset, usually in childhood </li></ul><ul><li>Complete insulin deficiency </li></ul><ul><li>Absolute insulin requirement </li></ul>
  6. 6. Type- II Diabetes Mellitus <ul><li>Pancreas doesn’t produce enough insulin or cells ignore it (insulin resistance) </li></ul><ul><li>Most people with diabetes have type 2 (85%), occurs after 40 years of age </li></ul><ul><li>Associated with obesity & runs in families to some extent </li></ul><ul><li>Lifestyle issues prominent </li></ul>
  7. 7. Gestational Diabetes Mellitus (GDM) <ul><li>Any degree of glucose intolerance with onset during pregnancy </li></ul><ul><li>Return to normal glucose regulation after delivery is common </li></ul><ul><li>Increased perinatal morbidity and mortality if untreated </li></ul>
  8. 8. Salient Clinical Symptoms <ul><li>Disease of mainly three P’s </li></ul><ul><li>Polydipsia- Excessive Thirst </li></ul><ul><li>Polyphagia- Excessive Hunger </li></ul><ul><li>Polyurea- Excessive Urination </li></ul><ul><li>Hyperglycemia </li></ul><ul><li>Tiredness </li></ul><ul><li>Loss of weight </li></ul>
  9. 9. Diabetes Mellitus - Complications
  10. 10. Complications of diabetes mellitus <ul><li>Acute (Metabolic) </li></ul>Chronic (Angiopathy) Macro Vascular Complications Micro Vascular Complications
  11. 11. Risk factors and complications Microvascular disease Eyes Kidneys Nerves Macrovascular disease Ischaemic heart disease Strokes Peripheral vascular disease Feet Hypertension Hyperglycaemia Dyslipidaemia Coagulopathy Smoking
  12. 12. Acute Complications <ul><li>Diabetic Ketoacidosis (DKA) </li></ul><ul><li>Hyperosmolar non-ketomic Coma (HONK) </li></ul><ul><li>Hypoglycemia </li></ul>
  13. 13. <ul><li>Metabolic injury to large vessels </li></ul>Biology of Macrovascular Injury Heart Brain Extremities <ul><li>Coronary artery disease </li></ul><ul><ul><li>– Coronary syndrome </li></ul></ul><ul><ul><li>– MI </li></ul></ul><ul><ul><li>– CHF </li></ul></ul><ul><li>Cerebrovascular disease </li></ul><ul><li>Peripheral vascular disease </li></ul><ul><ul><li>– Ulceration </li></ul></ul><ul><ul><li>– Gangrene </li></ul></ul><ul><ul><li>– Amputation </li></ul></ul>
  14. 14. <ul><li>Hyperglycemia </li></ul>Biology of Microvascular Injury <ul><li>Neuropathy </li></ul><ul><ul><li>Peripheral </li></ul></ul><ul><ul><li>Autonomic </li></ul></ul>Kidney Nerves Retinopathy - Cataract - Glaucoma <ul><li>Nephropathy </li></ul><ul><ul><li>Microalbuminuria </li></ul></ul><ul><ul><li>Gross albuminuria </li></ul></ul>Blindness Kidney failure Amputation Death and/or disability Eye
  15. 15. Microvascular Complications of Diabetes-1 <ul><li>Retinopathy: Damage to blood vessels in and around the retina. It could occur with varying degrees of severity. </li></ul>Normal -------------  Small hemorrhages ---------  Large hemorrhage
  16. 16. <ul><li>Nephropathy: </li></ul><ul><li>Glomeruli are damaged in the kidneys. </li></ul><ul><li>Results in loss of protein </li></ul><ul><li>DIAGNOSTIC VALUE- Normal microalbumin level is 30mg/24 hours. </li></ul><ul><li>May lead to kidney failure </li></ul>Microvascular Complications of Diabetes-2
  17. 17. Microvascular Complications of Diabetes-3 <ul><li>Neuropathy </li></ul><ul><li>Nerve fibres degenerate </li></ul><ul><li>Blood vessels supplying the nerves are ‘grossly diseased’ </li></ul>
  18. 18. Mechanism of Complications of Diabetes
  19. 19. Mechanisms causing diabetic complications-1 <ul><li>Accumulation of Sorbitol </li></ul><ul><li>Polyol (Polyhydroxy alcohols) Pathway </li></ul><ul><li>Sorbitol is formed from glucose catalyzed by aldose reductase </li></ul><ul><li>This pathway is activated in hyperglycemia </li></ul><ul><li>Sorbitol does not cross cell membranes, accumulates intracellularly and produces osmotic stress. </li></ul><ul><li>Sorbitol normally helps in osmoregulation </li></ul>
  20. 20. Consequences of high Sorbitol concentration <ul><li>Osmotic damage to cells: caused by impermeable Sorbitol intracellularly </li></ul><ul><li>Reduction in nerve myoinositol: causes decrease activity of Na/K ATP Pump- causes decreased nerve conduction velocity </li></ul><ul><li>Inhibition of nitric oxide (NO) production: results in vasoconstriction and hypertension </li></ul><ul><li>Increased production of free radicals: which cause oxidative damage to tissue </li></ul>
  21. 21. Mechanisms causing diabetic complications-2 <ul><li>Glycation of Proteins </li></ul><ul><li>Sugars in the blood and inside cells form chemical bonds to proteins and to DNA by glycation or nonenzymatic glycosylation. </li></ul><ul><li>Over time, the glycated proteins are chemically modified to become molecular structures called Advanced Glycation Endproducts (AGEs). </li></ul>
  22. 22. Pathological Consequences of Glycation of Proteins in Diabetics <ul><li>Crosslinking reduces the flexibility, elasticity and functionality of the proteins. </li></ul><ul><li>The chemical modifications of glycation and crosslinking can initiate harmful inflammatory and autoimmune responses. </li></ul><ul><li>Glycation has been found in connective tissue collagen, arterial collagen, kidney glomerular basement membrane, eye lens crystallins, nerve myelin proteins and in the circulating low-density lipoprotein ( LDL ) of the blood. </li></ul>
  23. 23. Diabetes is Managed, But it Does Not Go Away . <ul><li>GOAL: </li></ul>To maintain target blood glucose
  24. 24. Management Of Diabetes Mellitus <ul><li>The Fundamental Aim is - Glycemic Control </li></ul><ul><li>HbA1C < 7.0% </li></ul><ul><li>Pre-prandial PG 90 – 130 mg/dl </li></ul><ul><li>Postprandial PG < 180 mg/dl </li></ul><ul><li>Blood Pressure < 130/80 mmHg </li></ul><ul><li>Lipids - LDL < 100 mg/dl </li></ul><ul><li>Triglycerides < 150 mg/dl </li></ul><ul><li>HDL > 40 mg/dl </li></ul>
  25. 25. Management Of DM <ul><li>Step 1: Diet and Exercise to achieve Euglycemia. </li></ul><ul><li>If Euglycemia not achieved; Follow Step 2. </li></ul><ul><li>Step 2: Monotherapy with: </li></ul><ul><ul><li>Sulfonylurea </li></ul></ul><ul><ul><li>Bigunide </li></ul></ul><ul><ul><li>Glitazones </li></ul></ul><ul><ul><li>Meglitinides (Repaglinides) </li></ul></ul><ul><ul><li>Alpha-glucosidase </li></ul></ul><ul><li>Step 3: Addition of second oral agent or Insulin. </li></ul><ul><li>Consider Insulin therapy in Type I DM always. </li></ul>
  26. 26. THANK YOU