Impact of overweight and obesity on fasting insulin secretion in men and women without diabetes: effect sizes and mechanisms
Authors' conclusion
The effect of body mass on insulin secretion is continuous, more pronounced in men, driven by fat mass and waist, sustained by hyperglycaemia and by an upregulation of beta cell insulin secretion and is only partially explained by typical hormonal and metabolic consequences of obesity. We suggest that hepatic glucose overproduction contributes to the fasting hyperinsulinaemia observed in individuals with obesity.
Study context
- Population
- Healthy adults without diabetes aged 30–60 years, BMI 18.5–40.0 kg/m², EGIR-RISC cohort547 men · 703 women
- Participants
- 1,250 adults
- Outcome
- Fasting insulin secretion (FIS)
Methodological detailsEGIR-RISC cohort, 3.5-year follow-up, multivariable regression
- EGIR-RISC cohort
- 3.5-year follow-up
- Multivariable regression
Main finding
As reported in the abstract
Fat mass, standardised β coefficient
0.27
p<0.0001
Waist circumference, standardised β coefficient
0.21
p<0.0001
Insulin secretion increase across BMI deciles
2.4-fold
Observational data: associations, not effects.
Further findings
Change in fasting glucose with weight change · 3.5-year follow-up
- Weight gain (∆ weight +5.1 ± 3.8 kg): increase in fasting insulin secretion (FIS); fasting glucose change
- +0.20 ± 0.63 mmol/l, p<0.03
- Weight loss (−4.7 ± 2.8 kg): reduction in FIS; fasting glucose change
- +0.06 ± 0.55 mmol/l, p<0.006
Change in ISR@5 with weight change · 3.5-year follow-up
- Weight losers
- −0.17 ± 1.9 U/h, p<0.002
- Stable weight
- −0.16 ± 1.0 U/h, p<0.002
- Weight gainers (no decline)
- −0.06 ± 1.1 U/h
Mechanisms
- Peripheral insulin resistance, plasma NEFA and leptin accounted for only part of obesity's effect on insulin secretion
- Endogenous glucose production (EGP) subset: rightwards shift in dose-response across fat mass quintiles, progressive hepatic glucose overproduction despite preserved hepatic insulin response
- EGP measured in subset of 368
Original publication
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