(16) Type 2 Diabetes Phenotypes and Polyneuropathy: A Prevalence Study in The DD2 Cohort

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 690

Presenting Author(s)

Frederik Pagh Kristensen
– Aarhus University, Aarhus N, Midtjylland, Denmark

Co-Author(s)

Diana Christensen
– Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark., Denmark
Brian Callaghan
– Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA., United States
Helene Svane
– Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark., Denmark
Jacob Stidsen
– Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark., Denmark
Jens Nielsen
– Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark., Denmark
Kurt Højlund
– Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark., Denmark
Henning Beck-Nielsen
– Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark., Denmark
Troels Jensen
– Department of Neurology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark., Denmark
Henning Andersen
– Department of Neurology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark., Denmark
Peter Vestergaard
– Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark., Denmark
Niels Jessen
– Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark., Denmark
Michael Olsen
– Department of Regional Health Research, University of Southern Denmark, Odense, Denmark, Denmark
Torben Hansen
– Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark, Denmark
Charlotte Brøns
– Steno Diabetes Center Copenhagen, Odense University Hospital, Odense, Denmark, Denmark
Allan Vaag
– Steno Diabetes Center Copenhagen, Odense University Hospital, Odense, Denmark, Denmark
Henrik Toft Sørensen, MD, PhD, DMSc, DSc
– Professor & Chair, Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark, Midtjylland, Denmark
Reimar W. Thomsen, MD, PhD
– Professor, Aarhus University, Aarhus N, Midtjylland, Denmark

Background: The exact cause of diabetic polyneuropathy (DPN) in type 2 diabetes (T2D) remains unknown. Studies have suggested a clinical rationale for subgrouping T2D into 3 phenotypes of either insulinopenic (high insulin sensitivity, low beta-cell function), classical (low insulin sensitivity, low beta cell function), or hyperinsulinemic (low insulin sensitivity, high beta cell function). We hypothesized that patients with hyperinsulinemic T2D have the highest prevalence of DPN and that hyperinsulinemia per se is independently associated with DPN above and beyond other components of the metabolic syndrome.

Objectives: To investigate the association between hyperinsulinemia with DPN.

Methods: We included 3,397 recently diagnosed T2D patients (median diabetes duration 1y [IQR 0-3]) prospectively enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Cohort between 2010-2015. Insulin sensitivity and beta-cell function were quantified with the HOMA2 model based on baseline fasting serum C-peptide and plasma glucose levels. DPN was defined as a score of ≥4 when answering the Michigan Neuropathy Screening Instrument questionnaire sent out median 3 years after DD2 enrollment. We used multiple chained equation to impute missing values of potential confounders and applied Poisson regression to calculate age-, sex-, diabetes duration-, drug therapy- and lifestyle adjusted prevalence ratios (aPR) of DPN.

Results: We identified 900 (27%) hyperinsulinemic, 2,150 (63%) classical, and 347 (10%) insulinopenic T2D patients. Hyperinsulinemic patients had higher waist circumference (≥88/102 cm in females/males; 36% of insulinopenic, 75% of classical, 89% of hyperinsulinemic), more self-reported sedentary lifestyle (9%, 21%, 49%), higher triglycerides (≥1.7 mmol/L; 13%, 35%, 42%), but intermediate high HbA1c levels (≥7.5%; 8%, 12%, 6%). The aPR of DPN was 1.42 (95% CI 1.21-1.65) for hyperinsulinemic T2D patients, compared with the classical phenotype. The prevalence remained elevated (1.35 [1.15-1.57]) after further adjustment for central obesity, hypertriglyceridemia, hypertension, and HbA1c. For the insulinopenic patients, the partly and fully aPRs of DPN were 0.86 (0.65-1.14) and 1.03 (0.77-1.38), respectively. In additional spline analyses, increasing hyperinsulinemia was a strong driver of DPN even after adjusting for insulin resistance. In contrast, the effect of insulin resistance on DPN disappeared when adjusting for hyperinsulinemia.

Conclusions: The prevalence of DPN is increased in patients with the hyperinsulinemic T2D-phenotype. Hyperinsulinemia per se is associated with DPN, irrespectively of other metabolic factors.