Complications+of+Diabetes

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