Diabetes mellitus-Overview

• What is diabetes mellitus?

  It is a chronic disorder characterized by hyperglycemia due to several defects centered around insulin release & action.
• What are the possible causes of hyperglycemia?

  • Decreased entry of glucose into the cells
  • Decreased utilization of glucose by various tissues
  • Increased production og glucose by the liver (gluconeogenesis)
  • Decreased leveel of insulin/Insulin resistance
• What are the factors leadingt o the prevalence of DM?

  • Increasing age
  • Sedentary lifestyle
  • Unhealthy diet
• What is the major difference between Type I DM & Type II DM?

  Type I DM is due to insufficient insulin & Type II DM is due to insulin resistance
• What is the aetiology of Type I DM?

  • Total/near total insulin deficiency due to destruction of pancreatic B-cells
  • Autoimmune disease (Type IV hypersensitivity)
  • Secondary causes: Viral infections of pancreas/Toxins
  • Rapid onset
  • Mostly presents in young people
  • Strong geneetic link (HLA DR 3&4)
• What is the aetiology of Type II DM?

  • Impaired insulin secretion from pancreas
  • Insulin resistance in the tissues due to accumulation of amyloid peptide
  • Peripheral resistance to insulin is a post-receptor malfunction
  • No HLA link
  • Positive family history in 30% of patients
• Comparison of Type I & II DM

  • Type I is common in <20yrs while Type II is common in >30yrs
  • Type I is normal weight while Type II is obese
  • Type I has decreased insulin production while Type II has normal or increased insulin
  • Ketoacidosis is common in Type I but not in Type II
• What is the pathogenesis in Type I DM?

  Genetic susceptibility (HLA-linked)/Viral infections --> Autoimmune attack (B-cell destruction) --> Increased glucose production due to lack of insulin
• What is the pathogenesis in Type II DM?

  -Deranged insulin secretion

  -Insulin resistance: Reduced GLUTs

  -Obesity

  -Amylin: Accumulation causes pressure & necrosis of B-cells
• How to manage early morning hyperglycemia in patients with DM requiring insulin?

  • Increase the dose of insulin
  • Noctural surge of GH causes increased clearance of insulin
  • Results in diminution of insulin levels & causses breakthrough hyperglycemia
• What is the Somogyi phenomenon?

  • Patients with higher than required doses of insulin causes early morning hypoglycemia
  • Results in rebound hyperglycemia due to counterr regulatory hormone release (Epinephrine & glucagon)
  • Therefore, insulin dose has to be decreased
• Management of insulin dose

  Check the 3am blood glucose level

  • Hypoglycemia: Reduce the dose
  • Hyperglycemia: Increase the dose
• What are MOA of diabetic complications?

  Persistent exposure to high levels of sugars causes accumulation:

  • Osmotically active sugar (Sorbitol)-leads to massive damage to cells
  • Advanced Glycosylated End products in the tissues-due to non-enzymatic glycosylation (Glycation) of tissue proteins, LDL & HDL
• What is the MOA of glycation?

  • LDL/Cholesterol doubles the half-life of this lipoprotein
  • HDL results in quick clearance & decreased half life in the plasma
• How does AGE work?

  • AGE binding to cellular receptors
  • Macrophages release cytokines & growth factor
  • Leaky basement membranes of the vessel
  • Increased trapping of LDL/Cholesterol
• How does accelerated atherosclerosis in diabetes occur?

  Increased platelet adhesiveness:

  • Increased thromboxane A2
  • Decreased prostacyclin (potent vasodilator)

  Microangiopathy:

  • Thickening of capillary basement membrane
  • Increased cellular proliferation-Progressive narrowing of lumen of blood vessels
  • Subtypes: Retinopathy, Nephropathy & Vascular occulsions and gangrene in the eextremities
• What are the symptoms of hyperglycemia?

  • Thirst/Dry mouth
  • Polyuria/Nocturia
  • Fatigue
  • Weight loss
  • Blurring vision
  • Pruruitus vulvae (Genital candidiasis)
  • Nausea
  • Headache
  • Polyphagia
  • Mood change
• What are the acute complications of hyperglycemia?

  • Infections
  • Hypoglycemia
  • Comas- DKA in type I
• Why is hypoglycemia more common in Type I DM?

  • Due to administration of onsulin to keep fasting & post prandial blood sugar within the normal range

  -Results in a sympathetic stimulation (earliest warning sign)
• What are the diagnostic methods of hypoglycemia?

  • Symptoms of diabetes + a random plasma blood glucose concentration >200mg/dL
  • Fasting plasma glucose >126 mg/dL after an overnight fast
  • 2hr plasma glucose >200mg/dL during OGTT

  Glycosuria is not very reliable due to

  • False positives
  • Raised renal threshold
• When do you perform the OGTT?

  -Borderline fasting/Postprandial PG

  -Persistent glycosuria

  -Glycosuria of pregnancy

  -Pregnant women with family history of DM
• How do you perform OGTT?

  -Overnight fast

  -75g glucose in 300ml water given orally over 5 minutes

  -Basal plasma glucose & every 30 minutes for 2 hrs

  -Urine tested for sugar