Type 2 diabetes, elevated glucose associated with increased risk of unspecified dementia
Risk of Alzheimer's disease or vascular dementia was not associated with nonfasting plasma glucose levels in a large Danish study that included patients with and without diabetes.
A high level of nonfasting plasma glucose is causally related to a higher risk of unspecified dementia, but not to a higher risk of Alzheimer's disease or vascular dementia, a study found.
Researchers used a Mendelian randomization design to look at the association between high plasma glucose levels and risk of unspecified dementia, Alzheimer's disease, and vascular dementia in the general population and in patients with genetic variants that have been associated with lifelong elevated glucose concentrations but not increases in body mass index, blood pressure, or cholesterol levels. They used data from 125,875 Danish individuals from two prospective studies, the Copenhagen General Population Study and the Copenhagen City Heart Study. Results were published March 14 by Diabetologia.
Overall, 35% of individuals in the cohort had a baseline nonfasting plasma glucose concentration of less than 5.0 mmol/L (90 mg/dL), 42% had a baseline between 5.0 and 5.9 mmol/L (90 mg/dL and 106.2 mg/dL), 14% had a baseline between 6.0 and 6.9 mmol/L (108 and 124.2 mg/dL), and 8.4% had a baseline of 7.0 mmol/L (126 mg/dL) or greater. A total of 7,930 (6.3%) individuals had type 2 diabetes. Overall, 115,958 participants had glucose-associated genotypes available. During up to 43 years of follow-up (median, 10 years), 2,596 participants developed unspecified dementia, 2,287 developed Alzheimer's disease, and 493 developed vascular dementia.
In adjusted observational analyses, those with a glucose level higher than 7.0 mmol/L (126 mg/dL) versus 5.0 to 5.9 mmol/L (90 to 106.2 mg/dL) had hazard ratios of 1.15 (95% CI, 1.01 to 1.32; P=0.039) for unspecified dementia, 0.91 (95% CI, 0.79 to 1.06; P=0.22) for Alzheimer's disease, and 1.16 (95% CI, 0.86 to 1.55; P=0.34) for vascular dementia. Corresponding hazard ratios in individuals with type 2 diabetes, compared to those without, were 1.42 (95% CI, 1.24 to 1.63; P<0.001) for unspecified dementia, 1.11 (95% CI, 0.95 to 1.29; P=0.18) for Alzheimer's disease, and 1.73 (95% CI, 1.31 to 2.27; P<0.001) for vascular dementia. In genetic causal analyses, a 1-mmol/L (18-mg/dL) higher plasma glucose level had risk ratios of 2.40 (95% CI, 1.18 to 4.89; P=0.016) for unspecified dementia, 1.41 (95% CI, 0.82 to 2.43; P=0.22) for Alzheimer's disease, and 1.20 (95% CI, 0.82 to 1.75; P=0.36) for vascular dementia. Having more glucose-increasing alleles was associated with a trend of increased risk of unspecified dementia (but not the other types); adjusted for age and sex, those with a weighted glucose allele score in the 95th to 100th percentile had a hazard ratio of 1.24 (95% CI, 1.00 to 1.53; P=0.05) compared to those in the 0 to 24th percentile.
The study only captured individuals in contact with hospitals and was not able to pinpoint age of onset for types of dementia, among other limitations, the authors noted. “Our finding that high plasma glucose has a causal effect on the risk of unspecified dementia underscores the importance of glycaemic control in patients with diabetes mellitus and potentially also in individuals with impaired glucose tolerance,” they concluded. “Future research should address the causal role and potential disease mechanisms of plasma glucose on the risk of unspecified dementia.”