Dementia Risk According to Indices of Insulin Sensitivity and Beta-Cell Function in Individuals With Newly Diagnosed Type 2 Diabetes: A Cohort Study.
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.
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.
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.
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.
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.
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.
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.
Authors
Jensen Jensen, Kousholt Kousholt, Nielsen Nielsen, Stidsen Stidsen, Vaag Vaag, Thomsen Thomsen, Rungby Rungby, Kristensen Kristensen
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