Dataset Information

Risk of dementia and cognitive dysfunction in individuals with diabetes or elevated blood glucose.

ABSTRACT:

Aims

To determine the risk of dementia in patients with type 1 or type 2 diabetes and in individuals with glycosylated haemoglobin, type A1C (HbA1c) of ⩾48 mmol/mol, which is the diagnostic limit for diabetes.

Methods

We included the following cohorts: all incident diabetes cases aged 15 or above registered in the National Diabetes Registry (NDR) from January 2000 through December 2012 (n = 148 036) and a reference population, adult participants from the Glostrup cohort (n = 16 801), the ADDITION Study (n = 26 586) and Copenhagen Aging and Midlife Biobank (CAMB) (n = 5408). Using these cohorts, we analysed if a diagnosis of type 1 or type 2 diabetes in the NDR or HbA1c level of ⩾ 6.5% (48 mmol/mol) in the cohorts increased risk of dementia in the Danish National Patient Registry or cognitive performance assessed by the Intelligenz-Struktur-Test 2000R (IST2000R).

Results

A diagnosis of type 1 or type 2 diabetes in the NDR was associated with increased risk of dementia diagnosed both before or after age 65 as well as across different subtypes of dementia. Self-reported diabetes or high HbA1c levels were associated with lower cognitive performance (p = 0.004), while high HbA1c was associated with increased risk of dementia (HR 1.94 (1.10-3.44) in the Glostrup cohort but not in the ADDITION Study (HR 0.96 (0.57-1.61)).

Conclusions

Both type 1 and type 2 diabetes are associated with an increased risk of dementia, while the importance of screening-detected elevated HbA1c remains less clear.

SUBMITTER: Wium-Andersen IK

PROVIDER: S-EPMC8061228 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundRecurrent moderate hypoglycemia (RH), a major adverse effect of hypoglycemic therapy in diabetic patients, is one of the main risk factors for cognitive impairment and dementia. Transient receptor potential canonical channel 6 (TRPC6) is a potential therapeutic target for Alzheimer's disease (AD) and its expression is highly regulated by glucose concentration.ObjectiveTo investigate whether RH regulates the expression of TRPC6 in brain and whether TRPC6 dysfunction can drive hypoglycemia-associated cognitive impairment in diabetes, and reveal the underlying mechanism.MethodsHistological staining, in vivo two-photon Ca2+ imaging, and behavioral tests were used to measure neuronal death, brain network activity, and cognitive function in mice, respectively. High-resolution respirometry and transmission electron microscope were used to assess mitochondrial structure and function. Intracellular calcium measurement and molecular biology techniques were conducted to uncover the underlying mechanism.ResultsHere, we report that the expression of TRPC6 in hippocampus was specifically repressed by RH in streptozocin-induced type 1 diabetic mice, but not in nondiabetic mice. TRPC6 knockout directly leads to neuron loss, neuronal activity, and cognitive function impairment under diabetic condition, the degree of which is similar to that of RH. Activation of TRPC6 with hyperforin substantially improved RH-induced cognitive impairment. Mechanistically, TRPC6 inhibited mitochondrial fission in the hippocampus of diabetic mice undergoing RH episodes by activating adenosine 5'-monophosphate-activated protein kinase, and TRPC6-mediated cytosolic calcium influx was required for this process. Clinically, dysfunction of TRPC6 was closely associated with cognitive impairment in type 2 diabetic patients with RH.ConclusionsOur results indicate that TRPC6 is a critical sensitive cation channel to hypoglycemia and is a promising target to prevent RH-induced cognitive impairment by properly orchestrating the mitochondrial dynamics in diabetic patients.