• Credits
  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

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• Video:

• Q. Summarize the Pathogenesis of Type 2 Diabetes and its natural history with a picture ?

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• Q. How many islets of langerhans do we have and how many Beta-cells in each of them ?

  • We have 1 million islets of langerhans
  • Each islet has 1000 Beta-cells

• Q. What % of Beta-cells function is lost at the time of diagnosis of Type 2 Diabetes mellitus and what % is lost every year ?

  • 50% is lost at the time of diagnosis
  • 4-5% reduction every year

• Q. What does insulin output depend upon ?

  • It depends upon
    • 1. beta-cell mass
    • 2. beta-cell function

• Q. What is the current debate in the role of Beta-cells in Type 2 diabetes ?

  • The current debate is whether is there a reduction in beta-cell mass that leads to type 2 diabetes or it is reduction in beta-cell function that leads to diabetes

• Q. Why is this debate important ?

  • This is important because if there is only loss of function and not mass to potential of remission from disease is high
  • However, if there is a loss of mass and less issue with function- the potential of remission over a long term is questionable

• Q. What are Swisa's three models for Beta-cell failure in Type 2 Diabetes mellitus ?

  • 1. Reduced beta-cell number
  • 2. Beta-cell dysfunction due to (Also called beta-cell exhaustion )
    • Endoplasmic reticulum stress
    • Oxidative stress
  • 3. Compromised identity of Beta-cells
    • or Dedifferentiation / transdifferentiation of beta-cells
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• Q. First model - What leads to reduction of reduced beta-cell mass ?

  • 1. People may have low beta-cell to begin with (Fetal programming)
  • 2. Beta-cell may undergo apoptosis
  • 3. Aging leads to decline in beta-cell mass

• Q. Second model - What leads to reduced beta-cell function ?

  • 1. Endoplasmic reticulum stress
    • Endoplasmic reticulum stress is an important cause of beta-cell loss in both type 1 and Type 2 Diabetes mellitus
  • 2. Oxidative stress
  • This is where the phenomenon of Glucose Toxicity (Glucotoxicity) comes into picture
  • This is the recoverable part of Beta-cell dysfunction
  • There might be temporary stunning of beta-cells due to Hyperglycemia

• Q. ER Stress and Beta-cells

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• Q. Third model - compromised identity - Transdiffertiation of Beta-cells to other cells

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• Q. Of the above two models - which is more important ?

  • Model 2 is more important
  • This is because reduction of beta-cell mass can be compensated by increase in beta-cell function
  • A patient can have diabetes even with normal beta-cell mass
  • On the contrary- increase of beta-cell mass may not always compensate for reduced beta-cell function
  • This is a very important thing to understand
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• Q. According to a study, which drugs lead to how much of monotherapy failure?

  • At 5 years
    • Glyburide- 34%
    • Metformin- 21%
    • Rosiglitazone- 15%
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• Q. Enlist the various tests that are useful for the Assessment of beta-cell function ( beta-cell function ) in clinical practice ?

  • 1. Proinsulin:Insulin ratio
  • 2. HOMA-Beta
  • 3. Mixed meal stimulation test
  • 4. OGTT

• Q. What are the usual C-peptide in Fasting and post-meal states in euglycemic individual ?

  • Fasting - 0.9-1.8 ng/ml
  • Post -meal- 3-9 ng/ml

• Q. What is the best-cutt of blood C-peptide levels to determine insulin use in a post-prandial sample ?

  • 2 hour post meal- C-peptide <6 ng/dl (<2.02 nmol/l) is a stong predictor of insulin requirement

• Q. What is the interpretation of Random C-peptide value ?

  • The RBS >140 mg/dl for interpretation
  • Random c-peptide
    • <0.6 ng/ml ==> Absolute insulin deficiency
    • <1.8 ng/ml ==> Likely Type 1
    • 0.6-6.0 ng/ml ==> Requires mixed meal stimulation test
    • More than 6.0 ng/ml==> Rules out Type 1
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  • Convert nmol/l to ng/dl by multiplying by 3