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, 10, 2042018819889024

Impaired Compensatory Hyperinsulinemia Among Nonobese Type 2 Diabetes Patients: A Cross-Sectional Study


Impaired Compensatory Hyperinsulinemia Among Nonobese Type 2 Diabetes Patients: A Cross-Sectional Study

Jit Sarkar et al. Ther Adv Endocrinol Metab.


Aims: Obesity associated prolonged hyperinsulinemia followed by β-cell failure is well established as the pathology behind type 2 diabetes mellitus (T2DM). However, studies on nonobese T2DM have reported it to be a distinct clinical entity with predominant insulin secretory defect. We, therefore, hypothesized that compensatory hyperinsulinemia in response to weight gain is impaired in nonobese subjects.

Methods: This was a cross-sectional study from a community-based metabolic health screening program. Adiposity parameters including body mass index (BMI), waist circumference (WC), body fat percentage, plasma leptin concentration and metabolic parameters namely fasting insulin, glucose, total cholesterol, and triglycerides were measured in 650 individuals (73% healthy, 62% nonobese with a BMI <25).

Results: In contrast to obese T2DM, nonobese T2DM patients did not exhibit significant hyperinsulinemia compared with the nonobese healthy group. Age, sex, and fasting glucose adjusted insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA-beta cell function (HOMA-B) were increased in obese T2DM compared with nonobese T2DM. Although adiposity parameters showed strong correlation with fasting insulin in obese healthy (r = 0.38, 0.38, and 0.42, respectively; all p values < 0.001) and T2DM (r = 0.54, 0.54, and 0.66, respectively; all p < 0.001), only BMI and leptin showed a weak correlation with insulin in the nonobese healthy group (0.13 and 0.13, respectively; all p < 0.05) which were completely lost in the nonobese T2DM.

Conclusions: Compensatory hyperinsulinemia in response to weight gain is impaired in the nonobese population making insulin secretory defect rather than IR the major pathology behind nonobese T2DM.

Keywords: body mass index; hyperinsulinemia; leptin; nonobese; type 2 diabetes; β-cell failure.

Conflict of interest statement

Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.


Figure 1.
Figure 1.
Study design and insulin, HOMA-IR and HOMA-B in nonobese and obese T2DM: (a) flow diagram of the research study; (b) fasting insulin levels; (c) IR expressed as HOMA-IR; and (d) insulin secretion expressed by HOMA-B for healthy and T2DM groups in nonobese and obese BMI categories. Data represent the values as mean ± SE. **p < 0.01, ***p < 0.001.

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    1. Colditz GA, Willett WC, Stampfer MJ, et al. Weight as a risk factor for clinical diabetes in women. Am J Epidemiol 1990; 132: 501–513. - PubMed
    1. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab 2004; 89: 2583–2589. - PubMed
    1. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 2007; 356: 213–215. - PubMed
    1. Eckel RH, Kahn SE, Ferrannini E, et al. Obesity and type 2 diabetes: what can be unified and what needs to be individualized? Diabetes Care 2011; 34: 1424–1430. - PMC - PubMed
    1. Estampador AC, Franks PW. Precision medicine in obesity and type 2 diabetes: the relevance of early-life exposures. Clin Chem 2018; 64: 130–141. - PubMed

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