Short-term weight loss improves β-cell function in patients with obesity who have either normal or impaired fasting glucose (IFG). However, despite initial improvements, β-cell function commonly deteriorates over the course of 2 years, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The study included 58 participants with body mass index ≥35 kg/m2 (14 with normal fasting glucose, 24 with IFG, and 20 with type 2 diabetes [T2D]) and 13 normal-weight participants with normal fasting glucose. Patients with obesity were recruited from the University of Michigan Weight Management Program, an intensive 2-year intervention aimed at improving weight loss and reducing complications of obesity. For this study, participants underwent 3-hour mixed-meal tolerance tests to estimate insulin sensitivity, insulin secretion, and β-cell function, which the researchers defined as model-based insulin secretion adjusted for insulin sensitivity. After 3 to 6 months of follow-up, all 58 participants with obesity were restudied, and 27 completed a follow-up mixed-meal tolerance test at 2 years after baseline.

After 3 to 6 months on a very-low-energy diet, participants with obesity had a mean weight loss of 20 kg and a mean decrease in body mass index of 6 kg/m2.

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Compared with baseline, insulin sensitivity significantly improved among participants with obesity and normal fasting glucose (ratio of geometric means, 2.48; 95% CI, 1.64-3.74; P =.0004), IFG (ratio of geometric means, 2.52; 95% CI, 1.80-3.53; P <.0001), and T2D (ratio of geometric means, 2.43; 95% CI, 1.78-3.33; P <.0001). In addition, insulin secretion decreased significantly among participants with normal fasting glucose (ratio of geometric means, 0.58; 95% CI, 0.48-0.71; P <.0001) and IFG (ratio of geometric means, 0.62; 95% CI, 0.53-0.73; P <.0001). Among participants with T2D, insulin secretion showed a trend toward decreasing (ratio of geometric means, 0.84; 95% CI, 0.69-1.01; P =.061).

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For participants with obesity and normal fasting glucose, β-cell function trended toward improvement at 3 to 6 months after baseline (ratio of geometric means, 1.23; 95% CI, 0.94-1.61; P =.13). Among those with IFG, β-cell function also showed a trend toward improvement (ratio of geometric means, 1.17; 95% CI, 0.93-1.47; P =.18).

After 2 years of follow-up, and despite maintaining significant weight loss, the researchers found that β-cell function declined among participants with normal fasting glucose (ratio of geometric means, 0.82; 95% CI, 0.41-1.61; P =.40) and T2D (ratio of geometric means, 0.95; 95% CI, 0.66-1.35; P =.73). However, for those with IFG, β-cell function remained significantly improved compared with baseline (ratio of geometric means, 0.77; 95% CI, 0.64-0.92; P =.0076), indicating that these patients experienced the most persistent benefits of weight loss with regard to metabolic health.

The study had several limitations, including the use of insulin over C-peptide to assess β-cell function and the relatively small number of participants who completed follow-up at 2 years.

“This suggests that there is a window of opportunity to improve β-cell function in subjects with IFG, but that there is an irreversible fall in β-cell function with time in subjects with obesity and [T2D],” the researchers wrote.

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Rothberg AE, Herman WH, Wu C, et al. Weight loss improves β-cell function in people with severe obesity and impaired fasting glucose: a window of opportunity [published online November 13, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz189