Association between non-obese diabetes versus obese diabetes on dementia and mortality All of Us research program

TL;DR

Non-obese people with diabetes, especially type 1, face a higher dementia risk than obese diabetics or non-diabetics, according to a large US study.

Contribution

The study reveals that non-obese diabetes, particularly T1D, is linked to a significantly higher dementia risk compared to obese diabetes.

Findings

Non-obese T1D had a 4 times higher dementia risk compared to non-diabetic individuals.

Non-obese T2D showed a 1.82 times higher dementia risk compared to non-diabetic individuals.

The associations remained significant when accounting for mortality and using waist circumference as an obesity measure.

Abstract

Diabetes mellitus represents a significant risk factor for dementia, with both Type 1 and Type 2 diabetes contributing to cognitive decline through distinct mechanisms including insulin resistance, tau hyperphosphorylation, β-amyloid accumulation, chronic inflammation, and oxidative stress. To compare dementia risk between non-obese and obese individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) among US adults aged over 50 years, this retrospective study utilized data from the All of Us research program and ICD-9/10 codes to identify T1D, T2D, and dementia cases. Participants were classified as non-obese based on BMI (< 30 kg/m² for non-Asian races; < 27.5 kg/m² for Asian Americans) and waist circumference (< 102 cm for males, < 88 cm for females). Statistical analyses employed Cox-proportional hazard models and competing risk models accounting for mortality. Among 268,648 participants with a median follow-up of 10 (interquartile range, 6–14) years, 216 (17.8%) participants developed dementia. After full adjustment, non-obese T1D demonstrated a 4 times higher risk of dementia (95% CI: 2.86-5.60), while non-obese T2D showed a 1.82 times higher risk (95% CI: 1.45-2.28) compared to those without diabetes. These associations persisted when accounting for competing mortality risk and when using waist circumference as an obesity measure. Non-obese diabetes, particularly T1D, is associated with a significantly greater dementia risk compared to both obese diabetes and no diabetes. These findings underscore the importance of early cognitive screening, careful glycemic management, and targeted prevention strategies for non-obese individuals with diabetes.