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

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• Source: Ke, C et al.

• Q. What are the three key features of type 2 diabetes in Indian and Chinese populations?

  • 1. Younger age at diagnosis
  • 2. More beta-cell failure
  • 3. Leaner body habitus

• Q. What pathophysiological feature is seen in first-degree relatives of patients with type 2 diabetes that determines that there is probably a genetic component to diabetes?

  • Relatives of patients with type 2 diabetes have impaired first-phase and second-phase insulin secretion compared to other normal population
  • this may predispose them to develop type 2 diabetes in future

• Q. What is the key pathophysiological driver in patients with type 2 diabetes of South Asian origin and what studies have validated this?

  • The British Whitehall study, the MASALA, and the MESA studies looked at the pathophysiological differences in South Asians versus Europeans
  • They found that the HOMA-S was lower in South Asians compared to Europeans but in both cases declined with age
  • The HOMA-Beta- representing insulin response peaked 15 years earlier in South Asians and declined earlier compared to Europeans suggesting early exhaustion of compensatory mechanisms in South Asians compared to the Caucasians
  • This tells us that Beta-cell dysfunction occurs earlier in Indian patients with type 2 diabetes compared to Europeans

• Q. Apart from HOMA-Beta, what are the other methods by which you can determine the decline in beta-cell function over a period of time?

  • 1. Oral disposition index
  • 2. Glycemic deterioration over time - as evidenced by slipe of HbA1c over time

• Q. What is the formulation for Oral disposition index?

  • Oral disposition index = Insulin sensitivity index (Matsuda index) x insulin secretion index
    • Insulin sensitivity index = ISI = 10,000/square root of (Insulin at fasting × Glucose at fasting) × (mean glucose × mean insulin during OGTT) ==> note 75-g oral glucose test is used and blood samples were taken at 0, 30, 60, 90, and 120 min for the measurement of plasma glucose and insulin concentrations
    • Insulin secreation index = ΔI30/ΔG30 = (Ins30-Ins0)/(Glu30-Glu0)
      • Insulin and glucose at 30 minutes and baseline

• Q. In Indian patients with prediabetes- is there more IFG or more IGT?

  • There is more IFG compared to IGT
  • This is similar to non-caucasian cohorts in the US
  • The increase in IFG represents hepatic insulin resistance
  • HOMA-IR correlates well with hepatic insulin resistance

• Q. What is the distinct difference in the insulin resistance patterns in Indian versus the Chinese?

  • The Chinese have more Skeletal muscle insulin resistance and Indians have more hepatic insulin resistance
  • Hence Chinese Pre-diabetics have more IGT while Indians have more IFG
  • 

• Q. Summarize the key points in pathogenesis of Type 2 Diabetes mellitus in Indians

  • 

• Q. Which are the distinct alleles found from the GWAS study in the UK biobank in the Indian population that predispose them to develop Type 2 Diabetes?

  • HNF4A - Deals with insulin secretion
  • GRB14- deals with the action of insulin receptor
  • ST6GAL1- deals with insulin action
  • TMEM163- associated with insulin secretion

• Q. What are the broad interpretations from the UK biobank studies?

  • 1. Indians tend to have more issues with insulin secretion
  • 2. The alleles for subcutaneous adiposity are missing- hence Indians tend to have visceral adiposity

• Q. What are the common histopathological feature that is seen in Indian and Chinese type 2 diabetes patients?

  • Islet amyloid deposits in the pancreas are common in Indian and Chinese populations
  • They are seen in 40-100% of the patients

• Q. Summarize the genetic and environmental factors that contribute to the development of Type 2 Diabetes in the Indian and the Chinese?

  • 

• Q. What is the ANDIS classification of Diabetes mellitus?

  • Tags: Diabetes classification; Swedish cluster; Subtype of Diabetes; ANDIS classification
  • This is the classification of diabetes from the Swedish Cluster
  • SAID = Severe Autoimmune Diabetes
    • GAD antibodies, low insulin secretion, poor metabolic control
  • SIDD = Severe Insulin Deficient Diabetes
    • Low insulin secretion, poor metabolic control, increased risk of retinopathy
  • SIRD = Severe Insulin Resistant Diabetes
    • Insulin resistance, obesity, late-onset, marked increased risk of nephropathy
  • MOD = Moderate Obesity-Related Diabetes
    • Obesity, early-onset, good metabolic control
  • MARD = Moderate Age-Related Diabetes
    • Late-onset, good metabolic control, low risk of complications

• Q. What is the frequency of these clusters in the Indian cohorts?

  • The data from this comes from the INSPIRED and INDIAB studies
  • The frequencies are as follows:
  • 1. Severe insulin-deficient diabetes- 26-27%
  • 2. Severe insulin-resistant diabetes-7-12%
  • 3. Moderate obesity-related diabetes- 25-30%
  • 4. Mild age-related diabetes- 34-35%

• Q. What were the features of the Severe insulin-deficient diabetes cluster in the Indian population?

  • 1. It was more often compared to the Swedish (26% vs 17%)
  • 2. At younger age (42 vs 57 years)
  • 3. Lower BMI
  • 4. Lower beta-cell function
  • 5. lower insulin resistance
  • Interestingly even the severe insulin-resistant cluster of Indian patients had lower HOMA-Beta values (meaning more beta-cell dysfunction) compared to the Swedish cohort

• Q. Is the beta-cell decline in Young diabetics faster compared to others?

  • Yes
  • Type 2 diabetes before age of 40 years as studied in the TODAY trial showed more rapid deterioration of beta-cell function
  • this was evidenced by a rapidly declining oral disposition index at rate of 20-30% per year

• Q. Why are DPP-4 inhibitors more effective in the Indian population?

  • they say that it restores First phase insulin secreation earlier
  • hence more effective

• Q. What are the special issues with Thiazolidinones in the Asian population?

  • It seems that in the Asian population- the increased risk for heart failure hospitalization is not seen with these class of drugs
  • Tags: Pioglitazone

• Q. What are the summary and conclusion of this article?

  • 1. The age of onset of diabetes in the Indian population may be younger compared to the west. Diabetes before 40 years of age is very common
  • 2. Indian cohorts tend to have lower beta-cell function compared to the western cohorts. This is the key pathophysiological point and must be always kept in mind
  • 3. Severe insulin-deficient diabetes is a common cluster in the Indian subset of patients
  • 4. Overall, Indian diabetes is leaner and subcutaneous fat deposition is lesser
  • 5. Incretin-based therapies and AGI tend to do very well in the Indian subset of patients, especially when initiated when beta-cells are well preserved

Reference :

1. Ke, C., Narayan, K.M., Chan, J.C., Jha, P. and Shah, B.R., 2022. Pathophysiology, phenotypes, and management of type 2 diabetes mellitus in Indian and Chinese populations. Nature Reviews Endocrinology, pp.1-20