Physicians' Academy for Cardiovascular Education

Hyperglycemia can explain cognitive dysfunction in diabetic patients

The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive Performance – The Maastricht Study

Literature - Geijselaers SLC, Sep SJS, Claessens D, et al. - Diabetes Care 2017; published online ahead of print


Prediabetes and T2DM are associated with cognitive impairment [1]. The underlying pathophysiology is not absolutely clear, although markers of hyperglycemia, insulin resistance (IR) and vascular factors, like BP abnormalities, have been associated with cognitive dysfunction, irrespective of glucose metabolism status [2].

In this analysis of the Maastricht study, it was assessed whether the differences in cognitive performance between subjects with different glucose metabolism can be explained by the presence of hyperglycemia, IR, or BP-related variables. For this purpose, data from the first 3,451 participants included in the Maastricht study between November 2010 and September 2013 were used [3,4]. The glucose metabolism status was determined with a 2-h seven-sample oral glucose tolerance test (OGTT), and it was classified based on the 2006 WHO diagnostic criteria into normal glucose metabolism (NGM), impaired glucose metabolism (prediabetes), and T2DM. Patients with type 1 diabetes were excluded, and patients receiving insulin and those with a fasting glucose level >11.0 mmol/L were excluded from the OGTT, leaving a cohort with 2,531 participants.

Assessment of hyperglycemia was based on a composite index including fasting and post-load plasma glucose, as well as HbA1c, and tissue advanced glycation end products. For assessment of IR, the HOMA-IR index was used. Based on the recommendations of the British Hypertension Society, a composite index of SBP and DBP was used, which was derived from 24-h ambulatory BP data, and was combined with the use of antihypertensive medication. Moreover, a 24-h pulse pressure index was created.

Cognitive performance was measured by a concise neuropsychological test battery that lasts 30 min, and follows the recommendations for the assessment of diabetes-associated cognitive abnormalities [5]. In the current analysis, the raw test scores were standardized and divided into the cognitive domains of memory function, executive function plus attention (EF&A), and information processing speed.

Main results


In participants of the Maastricht study, differences in cognitive performance between T2DM patients and NGM individuals, could be explained by hyperglycemia and partially by BP-related variables, particularly in the domains of processing speed and executive function plus attention, whereas IR has no mediating effects. These findings suggest that the prevention of diabetes-associated deterioration of cognitive performance should focus on early glycemic and BP control.


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