Dementia Risk According to Indices of Insulin Sensitivity and Beta-Cell Function in Individuals With Newly Diagnosed Type 2 Diabetes : A Cohort Study
(2026) In European Journal of Neurology 33(3).- Abstract
Background: Insulin resistance and impaired insulin secretion are hallmarks of type 2 diabetes (T2D) and may influence risks of complications including dementia. We investigated dementia risk across T2D subgroups defined by beta-cell function and insulin sensitivity. Methods: We used Homeostasis Model Assessment-2 indices of beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) to classify 7221 individuals with recently diagnosed T2D into insulinopenic (low HOMA2-B, high HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and hyperinsulinemic (high HOMA2-B, low HOMA2-S) subgroups. Incident dementia was ascertained by validated hospital diagnosis codes and dementia-specific medication over 13 years. Absolute risks were estimated... (More)
Background: Insulin resistance and impaired insulin secretion are hallmarks of type 2 diabetes (T2D) and may influence risks of complications including dementia. We investigated dementia risk across T2D subgroups defined by beta-cell function and insulin sensitivity. Methods: We used Homeostasis Model Assessment-2 indices of beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) to classify 7221 individuals with recently diagnosed T2D into insulinopenic (low HOMA2-B, high HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and hyperinsulinemic (high HOMA2-B, low HOMA2-S) subgroups. Incident dementia was ascertained by validated hospital diagnosis codes and dementia-specific medication over 13 years. Absolute risks were estimated using the Aalen-Johansen estimator and adjusted hazard ratios (aHRs) using Cox regression. Results: Over a median follow-up of 9 years, 179 (2.5%) developed dementia. The 10-year risk (95% CI) was 3.8% (2.4%–5.8%) in the insulinopenic subgroup versus 2.8% in both classical (2.3%–3.5%) and hyperinsulinemic (2.0%–3.8%) subgroups. Compared with classical T2D, aHRs (95% CI) were 1.31 (0.83–2.09) for insulinopenic and 1.10 (0.78–1.54) for hyperinsulinemic T2D. No robust associations with dementia were observed with insulin resistance (HOMA-IR) or C-peptide levels, although compared to the lowest C-peptide levels (quartile 1), aHRs (95% CI) were decreased at 0.67 (0.45–1.01) in quartile 2, 0.73 (0.48–1.09) in quartile 3, and 0.89 (0.59–1.33) in quartile 4. Conclusions: We found no clear associations between T2D subgroup, insulin resistance, or C-peptide level at T2D diagnosis and dementia risk. The numerically higher risk in those with lower insulin secretion was statistically imprecise and warrants further study.
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- author
- Jensen, Nicole Jacqueline ; Kousholt, Astrid ; Nielsen, Jens Steen ; Stidsen, Jacob ; Vaag, Allan LU ; Thomsen, Reimar Wernich ; Rungby, Jørgen and Kristensen, Frederik Pagh Bredahl
- organization
- publishing date
- 2026-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- C-peptide, dementia, diabetes mellitus type 2, insulin resistance, insulin secretion
- in
- European Journal of Neurology
- volume
- 33
- issue
- 3
- article number
- e70527
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:41761701
- scopus:105031515059
- ISSN
- 1351-5101
- DOI
- 10.1111/ene.70527
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2026 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
- id
- ce7d8fa6-b94e-4f87-9bc6-bff625df4934
- date added to LUP
- 2026-04-20 15:49:57
- date last changed
- 2026-05-18 19:01:37
@article{ce7d8fa6-b94e-4f87-9bc6-bff625df4934,
abstract = {{<p>Background: Insulin resistance and impaired insulin secretion are hallmarks of type 2 diabetes (T2D) and may influence risks of complications including dementia. We investigated dementia risk across T2D subgroups defined by beta-cell function and insulin sensitivity. Methods: We used Homeostasis Model Assessment-2 indices of beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) to classify 7221 individuals with recently diagnosed T2D into insulinopenic (low HOMA2-B, high HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and hyperinsulinemic (high HOMA2-B, low HOMA2-S) subgroups. Incident dementia was ascertained by validated hospital diagnosis codes and dementia-specific medication over 13 years. Absolute risks were estimated using the Aalen-Johansen estimator and adjusted hazard ratios (aHRs) using Cox regression. Results: Over a median follow-up of 9 years, 179 (2.5%) developed dementia. The 10-year risk (95% CI) was 3.8% (2.4%–5.8%) in the insulinopenic subgroup versus 2.8% in both classical (2.3%–3.5%) and hyperinsulinemic (2.0%–3.8%) subgroups. Compared with classical T2D, aHRs (95% CI) were 1.31 (0.83–2.09) for insulinopenic and 1.10 (0.78–1.54) for hyperinsulinemic T2D. No robust associations with dementia were observed with insulin resistance (HOMA-IR) or C-peptide levels, although compared to the lowest C-peptide levels (quartile 1), aHRs (95% CI) were decreased at 0.67 (0.45–1.01) in quartile 2, 0.73 (0.48–1.09) in quartile 3, and 0.89 (0.59–1.33) in quartile 4. Conclusions: We found no clear associations between T2D subgroup, insulin resistance, or C-peptide level at T2D diagnosis and dementia risk. The numerically higher risk in those with lower insulin secretion was statistically imprecise and warrants further study.</p>}},
author = {{Jensen, Nicole Jacqueline and Kousholt, Astrid and Nielsen, Jens Steen and Stidsen, Jacob and Vaag, Allan and Thomsen, Reimar Wernich and Rungby, Jørgen and Kristensen, Frederik Pagh Bredahl}},
issn = {{1351-5101}},
keywords = {{C-peptide; dementia; diabetes mellitus type 2; insulin resistance; insulin secretion}},
language = {{eng}},
number = {{3}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Neurology}},
title = {{Dementia Risk According to Indices of Insulin Sensitivity and Beta-Cell Function in Individuals With Newly Diagnosed Type 2 Diabetes : A Cohort Study}},
url = {{http://dx.doi.org/10.1111/ene.70527}},
doi = {{10.1111/ene.70527}},
volume = {{33}},
year = {{2026}},
}