American Diabetes Association
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The prevalence of polyneuropathy in type 2 diabetes subgroups based on HOMA2 indices of beta-cell function and insulin sensitivity

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posted on 2023-06-19, 20:24 authored by Frederik Pagh Bredahl Kristensen, Diana Hedevang Christensen, Brian Christopher Callaghan, Jacob Volmer Stidsen, Jens Steen Nielsen, Kurt Højlund, Henning Beck-Nielsen, Troels Staehelin Jensen, Henning Andersen, Peter Vestergaard, Niels Jessen, Michael Hecht Olsen, Torben Hansen, Charlotte Brøns, Allan Vaag, Henrik Toft Sørensen, Reimar Wernich Thomsen



Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of beta-cell function and insulin sensitivity.


We estimated beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of three years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S.


3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. 


Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.


The DD2 study was supported by the Danish Agency for Science (grant numbers 09-067009 and 09-075724), the Danish Health and Medicines Authority, the Danish Diabetes Associa-tion, Region of Southern Denmark, and the Novo Nordisk Foundation (grant numbers NNF17SA0030962-2 and NNF20O0063292). The DD2 biobank was supported by an unre-stricted donation from Novo Nordisk A/S. Project partners are listed on the website


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