Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort analysis within an observational study
PubMed 28409212 · doi:10.1007/s00125-017-4275-6
What was done
Using data from the Whitehall II prospective British occupational cohort (1991–2013) with clinical examinations every 5 years, researchers analyzed ethnic differences in trajectories of glucose metabolism prior to incident type 2 diabetes. Trajectories of fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2-hour post-load serum insulin (2hSI), HOMA2 insulin sensitivity (HOMA2-S), HOMA2 beta-cell function (HOMA2-B), and the Gutt insulin sensitivity index (ISI 0,120) were modeled using cubic mixed-effects models adjusted for multiple covariates in 120 South Asian and 867 white participants who developed diabetes.
What was found
Compared with white individuals, South Asians had a faster increase in FPG prior to diagnosis (slope difference: 0.22 mmol/l per decade; 95% CI: 0.02, 0.42; p = 0.03) and higher FPG at diagnosis (difference: 0.27 mmol/l; 95% CI: 0.06, 0.48; p = 0.01). South Asians also had higher FSI and 2hSI levels before and at diagnosis, experienced a faster decline in insulin sensitivity, and had lower log-transformed HOMA2-S at diagnosis (difference: 0.33; 95% CI: 0.21, 0.46; p < 0.001) as well as lower ISI 0,120 levels throughout. HOMA2-B increased in both groups until 7 years before diagnosis before declining, with the initial increase being faster in white individuals. No ethnic differences were observed for 2hPG trajectories.
Why it matters
The findings demonstrate distinct pre-diagnostic pathophysiological trajectories between ethnic groups, characterized by steeper declines in insulin sensitivity and impaired beta-cell compensatory response in South Asian individuals compared with white individuals.
Limits
The study is restricted to an occupational cohort of British civil servants, limiting generalizability. The South Asian subpopulation was substantially smaller (n = 120) than the white subpopulation (n = 867). Insulin secretion and sensitivity were surrogate indices calculated from fasting and oral glucose tolerance tests rather than direct clamp measurements.
Cited by
- context By the time fasting blood sugar becomes elevated, a person has experienced pancreatic exhaustion of insulin production for at least a decade.