Evidence of reduced β-cell function in Asian Indians with mild dysglycemia

Abstract

Objective: To examine β-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI.

Research design and methods: One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and β-cell function (oral disposition index = [Δ insulin0-30/Δ glucose 0-30] × [1/fasting insulin]).

Results: Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m(2) (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each P < 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23-0.55; iIGT: OR, 0.37; 95% CI, 0.24-0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23-2.33; iIGT: OR, 1.53; 95% CI, 1.11-2.11).

Conclusions: Asian Indians with mild dysglycemia have reduced β-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of β-cell function.

Trial registration: ClinicalTrials.gov NCT01283308.

Figure 1

Age- and sex-adjusted mean oral disposition index and mean HOMA-IR across glycemic status. White bars indicate DI_o; filled triangles (▴) indicate HOMA-IR. Error bars indicate SE estimates. Geometric means and geometric SE were calculated for DI_o (L/mmol). HOMA-IR is presented as (mmol_glu × mmol_ins)/L²).