Elevated Fasting Blood Glucose Levels Are Associated With Lower Cognitive Function, With a Threshold in Non-Diabetic Individuals: A Population-Based Study

Abstract

Background: Cognitive dysfunction has been recognized as a diabetes-related complication. Whether hyperglycemia or elevated fasting glucose are associated with cognitive decline remains controversial. We aimed to investigate the relationship between fasting glucose levels and cognitive function in diabetic and non-diabetic individuals. Methods: Participants were Japanese diabetic (n = 191) and non-diabetic (n = 616) men, aged 46-81 years, from 2010-2014. Blood samples were taken after a 12 h fast. The Cognitive Ability Screening Instrument (CASI), with a maximum score of 100, was used for cognitive assessment. Cognitive domains of CASI were also investigated. Fractional logit regression with covariate adjustment for potential confounders was used to model cross-sectional relationships between fasting blood glucose and CASI score. Results: For diabetic individuals, CASI score was 0.38 (95% confidence interval: 0.66-0.12) lower per 1 mmol=L higher fasting glucose level. Short-term memory domain also exhibited an inverse association. For non-diabetic individuals, a reverse Ushaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance of 91.8 CASI score at 3.97-6.20 mmol=L (71.5-111.6 mg=dL) fasting glucose. Language ability domain displayed a similar relationship with fasting glucose. Conclusions: Elevated fasting glucose levels in diabetic men were associated with lower cognitive function, in which short-term memory was the main associated domain. Interestingly, in non-diabetic men, we identified a threshold for the inverse relationship of elevated fasting glucose with cognitive function. Contrastingly to diabetic men, language ability was the main associated cognitive domain among non-diabetic men.

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho

“…The linear association was independent of potential confounders including socio-demographics, health behaviors, and adiposity. Our findings corroborate results from several previous epidemiological studies showing dose-response relationships between fasting or postprandial blood glucose levels and cognitive deficits in non-diabetic elderly adults ( 5 – 7 ). The persistent adverse impact of elevated glucose on cognition across the spectrum highlights the need for early screening and preventive interventions even before the diagnosis of diabetes.…”

“…Numerous epidemiological studies have demonstrated that diabetes mellitus is one of the key risk factors for cognitive decline (2)(3)(4). Moreover, increased blood glucose levels are thought to be associated with cognitive impairment even among people without diabetes (5)(6)(7). For example, a prospective study found that a reverse U-shaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance at 3.97-6.20 mmol/L fasting glucose (5)., indicating impaired fasting glucose may be associated with cognitive impairment.…”

“…Moreover, increased blood glucose levels are thought to be associated with cognitive impairment even among people without diabetes (5)(6)(7). For example, a prospective study found that a reverse U-shaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance at 3.97-6.20 mmol/L fasting glucose (5)., indicating impaired fasting glucose may be associated with cognitive impairment. However, associations between blood glucose and cognition are inconsistent across different populations.…”

Pengaruh kadar gula darah puasa terhadap ekspresi Glucose transporter type-4 (GLUT4) neuron hipokampus pada tikus model diabetes

“…12 Peningkatan kadar gula darah puasa sering diasosiasikan dengan penurunan fungsi kognitif dan dapat menjadi salah marker dalam menilai gangguan fungsi kognitif. 13 Pada kondisi normal masuknya glukosa ke dalam sel diatur oleh insulin dan kecepatan transpor glukosa melalui suatu protein spesifik yang berikatan pada membran plasma yaitu glukosa tranpsorter (GLUT). GLUT sebagai protein transporter yang sudah diketahui dan dikenal dengan baik sebagai transporter glukosa adalah bentuk GLUT 1 sampai GLUT 14.…”

“…Mengingat kontrol kadar gula darah puasa yang normal sangat penting bagi tubuh dan peningkatan peningkatan kadar gula darah puasa dikaitkan dengan gangguan fungsi kognitif dan menjadi marker dalam menilai gangguan fungsi kognitif. 13 Serta satu penelitian menunjukkan ekspresi GLUT4 menurun pada kondisi terjadinya peningkatan kadar gula darah puasa pada penyakit DM. 17 Berdasarkan latar belakang yang diuraikan peneliti bertujuan untuk mengetahui pengaruh kadar gula darah puasa terhadap ekspresi GLUT4 neuron hipokampus pada tikus model diabetes yang diinduksi STZ dan NA.…”