Insulin resistance and cognitive performance in type 2 diabetes - The Maastricht study.
OBJECTIVE
Type 2 diabetes, hyperinsulinemia, and insulin resistance are associated with cognitive impairment. Experimental studies indicate that insulin signaling in the brain is related to cognitive performance. Here we evaluated whether insulin-related variables contribute to the variance in cognitive performance among individuals with type 2 diabetes.


METHODS
A total of 806 individuals with type 2 diabetes (mean age 62±8years, HbA1c 6.9±1.1%) completed a neuropsychological test battery. Insulin-related variables evaluated were: fasting plasma insulin, C-peptide, and the Homeostasis Model Assessment (HOMA2-IR; in individuals without insulin treatment; n=641). The unadjusted coefficient of determination (R2), obtained from multiple linear regression analyses, was used to estimate the proportion of variance in cognition explained by insulin-related variables.


RESULTS
Sex, age, and educational level together explained 18.0% (R2) of the variance in memory function, 26.5% in information processing speed, and 22.8% in executive function and attention. Fasting insulin, C-peptide, or HOMA2-IR did not increase the explained variance (maximum ΔR20.3%, P≥0.14). Similar results were obtained when insulin-related variables were added to models that additionally included glycemic control, cardiovascular risk factors, and depression.


CONCLUSIONS
Our results show that measures of peripheral insulin resistance are unrelated to cognitive performance among individuals with adequately controlled type 2 diabetes.
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: stefan.geijselaers@gmail.com.
Stefan L C
SLC
Geijselaers
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Simone J S
SJS
Sep
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Miranda T
MT
Schram
Department of Psychiatry and Neuropsychology and MHeNS School for Mental Health and Neuroscience, Maastricht University Medical Center +, Maastricht, the Netherlands.
Martin P J
MPJ
van Boxtel
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Ronald M A
RMA
Henry
Department of Psychiatry and Neuropsychology and MHeNS School for Mental Health and Neuroscience, Maastricht University Medical Center +, Maastricht, the Netherlands.
Frans R J
FRJ
Verhey
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Abraham A
AA
Kroon
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands; CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.
Nicolaas C
NC
Schaper
CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands; CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands; Department of Epidemiology, Maastricht University, Maastricht, the Netherlands.
Pieter C
PC
Dagnelie
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Carla J H
CJH
van der Kallen
Department of Internal Medicine, Maastricht University Medical Center +, Maastricht, the Netherlands; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Coen D A
CDA
Stehouwer
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Geert Jan
GJ
Biessels
D000328:Adult; D000368:Aged; D000375:Aging; D015415:Biomarkers / Q000097:blood; D060825:Cognitive Dysfunction / Q000150:complications* / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors
D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
C-peptide; Cognitive performance; Fasting insulin; Insulin resistance; Type 2 diabetes mellitus