Abstract Background Hyperinsulinemia is conventionally viewed as a compensatory response to insulin resistance primarily aimed at maintaining glycemic control. However, insulin also functions as a signal for energy conservation, promoting lipogenesis and inhibiting proteolysis. We hypothesized that chronic elevations in insulin drive a phenotype of preferential central adiposity and non-functional muscle preservation, detectable before the onset of hyperglycemia. Methods We analyzed cross-sectional data from 2,855 adults aged 18 years or older in the National Health and Nutrition Examination Survey (2011–2014). The primary exposure was fasting plasma insulin. The primary outcome was the ratio of grip strength to waist-to-height ratio (grip/WHtR). Multivariable linear regression models were adjusted for demographic and lifestyle factors and stratified by glycemic status. Results Fasting insulin was inversely associated with grip/WHtR (adjusted β per 1 μU/mL increase, −0.50; 95% confidence interval CI, −0.59 to −0.42; P0.001). The association was strongest in normoglycemic participants (β, −0.69; 95% CI, −0.86 to −0.51). Higher insulin concentrations were associated with significantly increased total body fat and appendicular lean mass but not increased grip strength. Mediation analysis revealed that adjusting for lean mass paradoxically strengthened the inverse association between insulin and grip/WHtR, indicating that insulin-associated muscle preservation did not translate to functional strength. Conclusions In a nationally representative sample, fasting insulin was strongly associated with an adverse body composition profile characterized by central adiposity and functionally inefficient muscle. This "reponic" phenotype is most pronounced in normoglycemic individuals, suggesting that hyperinsulinemia is an early, independent driver of metabolic dysfunction that precedes overt dysglycemia.
Droge et al. (Thu,) studied this question.