(P20-032-25) Effects of Significant Weight Reduction via Very Low Calorie Diet or Gastric Bypass on Beta Cell Function

Objectives: Obesity is a major risk factor for developing metabolic syndrome and type 2 diabetes mellitus (DM). Body weight is positively correlated with changes in insulin resistance and β-cell function, often preceding the onset of disease. Both Roux-en-Y gastric bypass (RYGB) and very low-calorie diets (VLCD) are effective weight loss strategies, but the mechanism underlying their effects on β-cell function remain unclear.

Methods: The development of metabolic syndrome is similar in both non-human primates (NHPs) and humans. Investigating metabolic syndrome in nonhuman primates poses multiple advantages, including a controlled diet and environment. This study investigated the impact of significant weight loss on β-cell function by comparing VLCD in obese NHPs to RYGB in obese humans. Fourteen spontaneously obese NHPs with and without DM were compared to 18 obese humans with and without DM.  β-cell function was assessed by measurement of acute insulin response (AIR) and disposition index (DI) at baseline and after 24 months of intervention.

Results: The AIR (µU/ml/min) in NHPs decreased after weight loss from 291 to 167 (p=0.025) in the obese group and increased from 17 to 42 (p=0.028) in the DM group. The AIR in obese humans decreased from 77 to 44 and increased in the DM group from 15 to 25. The DI in NHPs decreased after weight loss via VLCD from 2530 to 1732 (p=0.049) in the obese group and increased from 98 to 441 in the DM group. The DI in humans increased in both the obese and DM groups after weight loss from 1134 to 2226 and 339 to 1098, respectively (p = 0.017 and p = 0.003).

Conclusions: ß-cell function normalized in non-diabetic obese populations following weight loss, suggesting ß-cells hyperfunction in obese individuals. However, in diabetic populations, ß-cell function improved but did not entirely normalize, suggesting the inability ß-cells to fully recover in the case of overt DM.

Funding Sources: NIH National Institutes of Health, NIA National Institute on Aging
NIA HHSN263200800022C