The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of β-Cell Function and Insulin Sensitivity

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

Research output: Contribution to journalJournal articleResearchpeer-review


OBJECTIVE: 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 β-cell function and insulin sensitivity.

RESEARCH DESIGN AND METHODS: We estimated β-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 3 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.

RESULTS: A total of 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.

CONCLUSIONS: 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.

Original languageEnglish
JournalDiabetes Care
Issue number8
Pages (from-to)1546-1555
Publication statusPublished - Aug 2023


  • Diabetes Mellitus, Type 2/complications
  • Diabetic Neuropathies/epidemiology
  • Humans
  • Insulin Resistance
  • Metabolic Syndrome/epidemiology
  • Polyneuropathies
  • Prevalence


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