Association between Visit-to-Visit Glucose Variability and Cognitive Function in Aged Type 2 Diabetic Patients: A Cross-Sectional Study

Abstract

Background and PurposeDiabetes is associated with cognitive decline as well as the development of dementia. Although mean blood glucose levels are typically used to assess the status of diabetic patients, glucose variability is also involved in the manifestation of macro- and microvascular complications in this population. Thus, the present study sought to determine whether visit-to-visit glucose variability contributes to cognitive decline in patients with type 2 diabetes.MethodsThe present study assessed 68 patients with type 2 diabetes using several validated neuropsychological measures. All patients had no cerebrovascular disease, history of hypoglycemia, psychiatric conditions, or other medical illnesses. Standard deviations (SDs) and coefficients of variance (CVs) of the patients’ blood glucose (after fasting and 2 hours postprandial; FBS and PP2), and glycated hemoglobin (HbA1c) values were used as indices of glucose variability. The cognitive outcome parameters were transformed with z-scores and entered into a multiple linear regression model that included educational status, age, sex, vascular risk factors, and mean glucose parameters as covariates.ResultsThe mean age of the total patient population was 70.9 years; 46 (67.6%) of the patients were men, and the median follow-up duration at our endocrinology outpatient clinic was 4.8 years. The mean FBS and PP2 glucose levels of the patients were 132 mg/dL and 199 mg/dL, respectively, and the mean HbA1c level was 8.0%. A univariable analysis revealed that only the PP2 value was associated with the Mini-Mental State Examination (MMSE) score, and multivariable analysis revealed that a high SD and/or CV for PP2 glucose were associated with low scores on the Rey Complex Figure Copy test and/or the Verbal Learning Test. Additionally, a high SD and a higher CV for HbA1c level were significantly associated with low MMSE and Digit Span test scores even after adjusting for mean HbA1c values.ConclusionsThe present data indicate that a greater degree of visit-to-visit glucose variability influenced specific types of cognitive function in type 2 diabetic patients independently of mean blood glucose levels. Future studies should focus on whether reductions in glycemic variability will improve the cognitive decline observed in type 2 diabetic patients.

Impact of postprandial glucose control on diabetes-related complications: How is the evidence evolving?

“…Postprandial hyperglycemia has also been associated with an increase in the risk of cognitive dysfunction [40,41], and pancreatic, colorectal and breast cancers [42][43][44]. A recent study of 68 individuals with type 2 diabetes revealed that the mean 2-hour PPG value (univariable analysis), and "visit-to-visit" 2-hour PPG variability (multivariable analysis) was associated with cognitive decline in standardized tests over a median 4.8-year period [41].…”

“…A recent study of 68 individuals with type 2 diabetes revealed that the mean 2-hour PPG value (univariable analysis), and "visit-to-visit" 2-hour PPG variability (multivariable analysis) was associated with cognitive decline in standardized tests over a median 4.8-year period [41]. PPG levels also correlated with cancer mortality.…”

Ambulatory glucose profile in diabetes‐related dementia

“…There is growing evidence that DM carries greater risks of cognitive decline and dementia compared with healthy individuals . Studies have reported that hyperglycemia, hypoglycemic episodes, postprandial glucose excursions and glucose variability might contribute to cognitive impairment and brain atrophy in individuals with DM . In addition to cerebrovascular diseases, several mechanisms, such as impaired neuronal insulin signaling, inflammation, mitochondrial dysfunction and oxidative stress, β‐amyloid accumulation, and tau phosphorylation, have been proposed for neuronal damage associated with DM .…”

Diabetes type 2 diabetes in the elderly – solved and unsolved questions

“…При изучении гликемического контроля у 337 пациентов пожилого возраста с СД2 с помощью НМГ выявлено, что женский пол, продолжительность диабета, уровень гликированного гемоглобина являются значимыми фак-торами влияния на вариабельность гликемии, в то время как сам по себе возраст не имеет ассоциации с вариабель-ностью гликемии у данных пациентов [28]. Тем не менее, высокая вариабельность гликемии -более значимый показатель неблагоприятного воздействия диабета на когнитивную функцию пожилых лиц, чем средний уро-вень гликемии [29]. В исследовании китайских ученых показана положительная прямая связь между высокой вариабельностью гликемии и наличием и тяжестью сердечно-сосудистых заболеваний (ССЗ) у пациентов с СД2 [30].…”