medwireNews: Type 2 diabetes in young, lean people is much more common in Asian Indians than in White Europeans, say researchers who found that genetically determined beta-cell function may be to blame.
Ewan Pearson (University of Dundee, UK) and colleagues drew data from the ICMR-INDIAB study (n=1712) and Dr Mohan’s Diabetes Specialties Centre (DMDSC; n=54,989) cohorts of Asian Indians with newly diagnosed type 2 diabetes. They highlight their focus on non-migrant populations, in contrast with many previous studies.
The median age at diagnosis was “dramatically lower” in these Indian cohorts than in 42,563 White European individuals from the East Scotland Diabetes Cohort, at 47–50 versus 62 years, reports the team in Diabetologia.
Moreover, 24–39% of Indian people were classified as having a healthy BMI at the time of diagnosis, compared with just 9.3% of the White Europeans, based on ethnic-specific cutoffs of less than 23 kg/m2 for Asian Indians and 25 kg/m2 for White Europeans.
Asian Indians diagnosed at the age of 40 years or younger had an identical median BMI to those diagnosed when older, but they had significantly lower fasting and stimulated C-peptide and poorer beta-cell function, yet were more insulin-sensitive. In addition, they more often had a family history of diabetes (69 vs 44%).
And among Asian Indians diagnosed young, those with a healthy BMI had lower C-peptide levels and poorer beta-cell function than people with an overweight or obese BMI. Conversely, they were more insulin-sensitive and had more favorable lipid profiles.
When the researchers assessed seven genetic variants associated with poor beta-cell function, they found these to be significantly more frequent in the Asian Indians than in the White Europeans in their study cohorts and also in people from the UK Biobank, with approximately 45% versus 25% having at least eight risk alleles.
However, Pearson and team caution that these variants were identified in White European cohorts, and that studies in Asian people might “produce a different or expanded set of candidate [single nucleotide polymorphisms] for beta cell function.”
Overall, they conclude that their findings point to poor beta-cell function as a factor underlying the high proportion of relatively young, lean people with type 2 diabetes in India.
The researchers say: “The demographics of India are changing, with more urbanisation and a shift to sedentary jobs. It is likely that, against the background of poor beta cell function and lower muscle mass, smaller increases in ectopic fat and adiposity may drastically increase diabetes risk.”
Nevertheless, they emphasize “that the substantive proportion” of diabetes in younger people occurred in those with obese BMIs, and point out that these people also had elevated levels of the liver enzyme alanine aminotransferase (ALT).
“This is suggestive of higher ectopic fat deposition, as ALT is a reasonable correlate of ectopic fat, consistent with the hypothesis of the ‘thin–fat’ phenotype that has been suggested to predispose Asian Indians to type 2 diabetes,” writes the team.
“This mirrors the more classic insulin resistance aetiology of diabetes.”
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