Fasting hyperinsulinemia persists across type 2 diabetes duration without exogenous insulin
- 1University of California Davis
Abstract
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 with HbA1c-confirmed T2D for [≥]15 years 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.
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BibTeX
@misc{mirza2026fasting,
title = {{Fasting hyperinsulinemia persists across type 2 diabetes duration without exogenous insulin}},
author = {S. Mirza and N. Ernst and J. Moen},
howpublished = {medRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.27.26358997},
url = {https://www.medrxiv.org/content/10.64898/2026.07.27.26358997v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fasting hyperinsulinemia persists across type 2 diabetes duration without exogenous insulin
AU - S. Mirza
AU - N. Ernst
AU - J. Moen
PY - 2026
DA - 2026/07/27
PB - medRxiv
DO - 10.64898/2026.07.27.26358997
UR - https://www.medrxiv.org/content/10.64898/2026.07.27.26358997v2
AB - 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 with HbA1c-confirmed T2D for [≥]15 years 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.
ER -