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Beta cell function in Asian Indians: evidence for marked declines

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.

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 = [Δinsulin0–30/Δglucose0–30] × [1/fasting insulin]).

RESULTS Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m2 (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.

Type 2 diabetes mellitus is a global problem, with 80% of all cases worldwide occurring in low- and middle-income countries (1). However, despite the increasing prevalence of type 2 diabetes, the etiology of the disease remains incompletely understood. Previously invoked as the driving feature of diabetes, increased insulin resistance can trigger increased insulin production to maintain normoglycemia and, over time, can strain β cells to the point at which insulin production is no longer adequate (2–4), i.e., β-cell “exhaustion.” Characteristics associated with insulin resistance, particularly older age, obesity, and physical inactivity, are strong risk factors for diabetes (5).

Yet, poor β-cell function also may have more of a primary role in diabetes development. The inadequate β-cell response to physiologic needs for insulin not only may be an acquired feature (e.g., as a result of insulin resistance) but also, at least in some individuals, may be an inherent feature. β-Cell dysfunction has been detected early in the pathogenesis of the disease (6), with recent cross-sectional and longitudinal studies detecting dysfunction in people with prediabetes or even normoglycemia (7–10). Supported by recent genetic discoveries (11), these studies suggest that some individuals have an underlying susceptibility to poor β-cell function (12) and that β-cell dysfunction may be an early driving metabolic feature of diabetes development.

Most studies of diabetes pathogenesis have been conducted in populations of European descent; however, more people have diabetes in other populations worldwide. Asian Indians, in particular, experience high rates of type 2 diabetes (13) at younger ages and lower BMI values (14) compared with other populations. They have high basal insulin levels (15) that are not entirely explained by obesity or adverse fat distribution (16), which are commonly cited factors related to insulin resistance. Considering these characteristics, Asian Indians may be an ideal population to utilize for developing a better understanding of the relative roles of β-cell function and insulin resistance in the pathogenesis of type 2 diabetes. Previous studies that have examined the etiology of diabetes in Asian Indians have produced conflicting findings. Altered β-cell function has been associated with impaired glucose tolerance (IGT) (17), has not been associated with IGT (18,19), and has been associated with impaired fasting glucose (IFG) but not IGT (20). Furthermore, β-cell function has not always been evaluated rigorously in Asian Indians (i.e., expressed relative to the insulin resistance of each individual) (21). We investigated the associations between the pathophysiologic mechanisms of insulin resistance and β-cell function with glycemic status in a large cohort (n = 1,264) of Asian Indians in Chennai, India.

 

By Ronan
Mar 16, 2015
14:05
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