Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study

Abstract

Aims/hypothesisSouth Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants.MethodsIn a prospective British occupational cohort with 5-yearly clinical examinations (n = 230/5,749 South Asian/white participants, age 39–79 years at baseline), age-related trajectories of fasting glucose (FG) and 2 h post-load glucose (PLG), log-transformed fasting insulin (FINS) and 2 h post-load insulin (PLINS), HOMA insulin sensitivity (HOMA2-%S) and HOMA insulin secretion (HOMA2-%B) were fitted for South Asian and white individuals who remained free of diabetes between 1991 and 2009.ResultsIn sex-adjusted multilevel models, FG was stable in white participants but increased with age in South Asians (0.12 [SE = 0.04] mmol/l per decade). PLG, FINS and PLINS levels were lower among white participants (by 0.271 [SE = 0.092] mmol/l, 0.306 [SE = 0.046] log pmol/l, 0.707 [SE = 0.059] log pmol/l at age 50, respectively) compared with South Asians, although their age-related trajectories were parallel. HOMA2-%S was higher (0.226 [SE = 0.038] at age 50) and HOMA2-%B lower (by 0.189 [SE = 0.026] at age 50) among white than South Asian participants. The age-related decline in HOMA2-%S was similar in these groups, but the age-related increase in HOMA2-%B was greater in white participants (0.04 [SE = 0.02] per decade). This difference was explained by obesity, lifestyle and social status.Conclusions/interpretationFindings from a diabetes-free population suggest an inadequate pancreatic beta cell reserve in South Asians, as a significantly steeper age-related increase in FG was observed in this ethnic group compared with white individuals.

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

“…This suggests that they managed to compensate for their higher insulin resistance for many years until a steep decline in insulin secretion (and probable beta cell exhaustion) in the 5–7 years before diagnosis. In combination, these findings support the hypothesis that South Asians exhibit long-term beta cell compensation for chronic insulin resistance from childhood and that they are unable to produce further beta cell compensation in response to decreasing insulin sensitivity above 60 years of age [3]. Whether these differences are innate or related to the deleterious effects of some environmental factors is a question that our study is currently unable to answer.…”

“…We have also identified subgroups with different trajectories of insulin sensitivity and secretion prior to the development of diabetes, suggesting important heterogeneity in the relative contributions of insulin sensitivity and secretion before diagnosis of type 2 diabetes [15]. Longitudinal modelling of age-related changes in insulin sensitivity and insulin secretion among individuals without diabetes has shown a lack of compensatory increase in insulin secretion among South Asian compared with white individuals, supporting the hypothesis of a reduced pancreatic functional reserve in this high-risk group [3]. However, ethnic differences in the natural history of early changes in glucose metabolism prior to incident type 2 diabetes are not well understood, precluding optimal timing for screening and prevention activities among South Asian people.…”

Tale of two Indians: Heterogeneity in type 2 diabetes pathophysiology

“…In a separate study examining normal weight US adults, 21.0% of non‐Hispanic whites, 31.1% of African Americans, 38.5% of Hispanics, and 43.6% of South Asians were metabolically unhealthy yet thin, and South Asians had poorer pancreatic beta‐cell function compared with whites, blacks, and Hispanics . Similarly, an analysis from the Whitehall II cohort study in the UK suggested that South Asians may have a poorer beta‐cell reserve relative to white Europeans . These studies support the hypothesis of Phenotype 2b describing high‐risk individuals with narrow beta‐cell capacity.…”

Association between alcohol consumption pattern and the incidence risk of type 2 diabetes in Korean men: A 12-years follow-up study

“…However, pancreatic β-cell function, estimated by the IGI 60 , had an inverted J-shaped trend. Several recent studies have suggested that impaired β-cell function has a greater effect on the development of diabetes than does insulin resistance in Asian people 18 – 21 . We previously showed that heavy alcohol consumption was associated significantly with reduced insulin secretion, but not insulin sensitivity, in Koreans 22 .…”