Fasting hyperinsulinemia persists across type 2 diabetes duration without exogenous insulin

Declining insulin with longer type 2 diabetes (T2D) duration is commonly interpreted as beta-cell failure. We analyzed NHANES data from 2003-August 2023 cross-sectionally and 2007-2018 with mortality linkage. The primary harmonized analysis included 2,072 adults with diagnosed T2D, calculable duration, and no exogenous insulin, and 9,050 normoglycemic adults. Across durations of <5, 5-14, and 15+ years, adjusted insulin ratios versus normoglycemia were 2.39 (95% CI 2.20-2.60), 1.88 (1.76-2.00), and 1.71 (1.58-1.86). A sensitivity restricted to current laboratory diabetes without exogenous insulin or secretagogues (n=808) yielded ratios of 2.21, 1.86, and 1.88. Among adults aged 75 years or older with HbA1c-confirmed T2D for 15 years or longer and no exogenous insulin or secretagogue, the ratio was 1.73 (1.36-2.21; n=37). In the prespecified primary mortality analysis of the most recent six-cycle NDI-linked window, 2007-2018, insulin was associated with cardiovascular mortality in prediabetes (hazard ratio 2.95, 1.70-5.11). Hyperinsulinemia persisted across T2D duration and advanced age, arguing against uniform insulin deficiency in long-duration non-insulin-treated T2D. Mortality associations differed by disease stage and survey period.