Adipose Tissue Insulin Resistance Is Longitudinally Associated With Adipose Tissue Dysfunction, Circulating Lipids, and Dysglycemia: The PROMISE Cohort

Research design and methods: Adults at-risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n=468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and non-esterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and sCD163), circulating lipids (total cholesterol, HDL, LDL, TG), and systemic inflammation (Il-6 and TNF-α). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes.

Results: GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin: -4.20% (95%CI, -6.40 to –1.95); sCD163: 4.36% (95%CI, 1.73 – 7.06), HDL (-3.87% (95%CI, -5.15 to -2.57)) and TG (9.26% (95%CI, 5.01 to 13.69)). Adipo-IR was associated with increased risk of incident dysglycemia (OR=1.59; 95%CI, 1.09 to 2.31, per SD increase). Associations remained significant after adjustment for waist circumference, and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with Il-6, TNF-α, total cholesterol, or LDL.

Conclusion: Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.