Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes

Abstract

Objective Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes. Methods A retrospective cohort study of 777 randomly selected participants from ~11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (±9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects’ performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization. Results Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r = −0.166, p = 0.011), executive functions (r = −0.136, p = 0.038), and overall cognition (r = −0.157, p = 0.016). Conclusions Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes.

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

“…CRP-associated impaired memory was also described in type II diabetes patients. 58 However, no association was observed between abnormal CRP and long-term verbal recall impairment in SZ. Memory impairment related to inflammatory processes is less clear in depression.…”

Day-to-day fasting glycaemic variability in DEVOTE: associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2)

“…Grouping patients into thirds to investigate variability has been used in previous studies [30–32]. Example SMBG profiles for three separate DEVOTE patients can be seen in Fig.…”

“…For the purposes of summarising the baseline characteristics by low and high day-to-day fasting glycaemic variability, the patient population was divided into tertiles or thirds defined by low, medium and high variability. Grouping patients into thirds to investigate variability has been used in previous studies [ 30 – 32 ]. Example SMBG profiles for three separate DEVOTE patients can be seen in Fig.…”

Dopamine Adaptations as a Common Pathway for Neurocognitive Impairment in Diabetes and Obesity: A Neuropsychological Perspective

“…This poses a problem for interpreting the pathophysiology of the link between T2D and cognition because individuals with chronic T2D exhibit a number of pathologies associated with cognitive decline such as damage to the blood brain barrier (BBB), neuroinflammation (Banks et al, 2012; Steculorum et al, 2014), cerebral atrophy, and small vessel disease (Biessels and Reijmer, 2014; Akrivos et al, 2015; Ramos-Rodriguez et al, 2016; Stranahan et al, 2016). The co-occurrence of these pathologies that are secondary to diabetes has led to controversy over whether it is T2D (Biessels and Reagan, 2015) or complications arising from T2D that leads to cognitive decline (De Felice and Ferreira, 2014).…”