Fasting glucose and homeostatic model assessment-insulin resistance (HOMA-IR) are important measures of the risk for metabolic syndrome and diabetes. Weight loss interventions are considered part of the first line of therapy for those who develop disease states associated with insulin resistance, such as pre-diabetes, diabetes, or metabolic syndrome. Sex differences in insulin resistance have been extensively reported, but sex differences in the ability to improve insulin sensitivity are not well-established. This study sought to identify factors that predict change in HOMA-IR in response to weight loss.


Non-diabetic subjects who were overweight/obese (n=100) were randomly assigned to a walnut-enriched reduced-energy diet or a standard reduced-energy-density diet in a 6-month weight loss intervention. There were no significant differences in weight change, glucose, insulin, or HOMA-IR between the two diet groups. These subjects were combined into a single cohort and analyzed with multivariate analysis.


The combined groups lost an average of 8.7 kg (p<0.0001), decreased serum glucose by an average 0.2 mmol/L (p<0.001), and decreased HOMA-IR by an average of 1.4 (p<0.0001). Change in HOMA-IR (R2=0.69) was positively associated with weight change (p<0.0001) and male sex (p<0.01), and negatively associated with baseline HOMA-IR (p<0.0001).


Findings from this study suggest that men may have a more difficult time improving insulin sensitivity as compared with women with an equivalent weight loss and baseline HOMA-IR. One hypothesis to explain the differences across sexes may be due to sex differences in visceral adipose fat (VAT). This may mean that insulin resistant men require more aggressive intervention than women to prevent progression to metabolic syndrome or diabetes.

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