Effects of intensified metabolic control on CNS function in type 2 diabetes

The mild cognitive decline associated with type 2 diabetes (T2DM) has been suggested to be reversible with improved glycemic control. In order to characterise this cognitive decline and study the effects of improved glycemic control we have studied patients with T2DM (N=28) and healthy control subjects (N=21). One group of patients with diabetes (N=15) were given a 2-month treatment of intensified glycemic control, whereas the other group (N=13) maintained their regular treatment. Cognitive function in four different domains, auditory event-related potentials (ERPs) and resting EEG power spectrum were studied in the two groups of patients and in healthy control subjects before and after the 2-month trial period. There were significant differences at baseline (p<0.02) between patients with T2DM and controls. Patients had lower scores in two cognitive domains: verbal fluency (p<0.01) and visuospatial ability (p<0.03). T2DM also affected ERP with a decrease in N100 amplitude (p<0.04) and an increase in P300 latency (p<0.03). Furthermore, resting EEG activity in the beta band (13-30Hz) was reduced (p<0.04). The change between 1st and 2nd investigation was significantly different in the three groups of patients/subjects (p<0.03). Patients receiving intensified treatment for glycemic control had an improvement of cognitive ability in visuospatial ability (p<0.02) and semantic memory performance (p<0.04) together with increased resting EEG activity in the alpha band (8-13Hz, p<0.02) and connectivity in the theta (4-8Hz, p<0.03) and alpha bands (p<0.03) over central and lateral regions. Furthermore, there was an increase in the connectivity in the beta band (p<0.04) over the central regions of the scalp. In conclusion, subjects with T2DM had a similar type of cognitive function impairment and EEG/ERP abnormality as previously demonstrated for subjects with type 1 diabetes (T1DM). Intensified therapy showed cognitive improvement not shown for regular treatment, suggesting that the negative effect of T2DM on cognition is reversible by means of improved glycemic control. Furthermore, there was an improvement in electro-physiological measures, suggesting increased availability of compensatory mechanisms in subjects with intensified treatment.

[1]  Geert Jan Biessels,et al.  The effects of type 1 diabetes on cognitive performance: a meta-analysis. , 2005, Diabetes care.

[2]  A. Verma,et al.  Cognitive dysfunction in NIDDM: P3 event related evoked potential study. , 1999, Indian journal of physiology and pharmacology.

[3]  R. Kronmal,et al.  The Cardiovascular Health Study: design and rationale. , 1991, Annals of epidemiology.

[4]  U. Hadar,et al.  Cognition in stroke , 1994, Acta neurologica Scandinavica.

[5]  M. Thorén,et al.  Altered relation between circulating levels of insulin-like growth factor-binding protein-1 and insulin in growth hormone-deficient patients and insulin-dependent diabetic patients compared to that in healthy subjects. , 1995, The Journal of clinical endocrinology and metabolism.

[6]  M. Gagnon,et al.  Glucose and Glucoregulatory Modulation of Memory Scanning, Event-Related Potentials and EEG in Elderly Subjects , 2001, Neuropsychobiology.

[7]  P. Cleary,et al.  Long-term effect of diabetes and its treatment on cognitive function. , 2007, The New England journal of medicine.

[8]  A. Convit,et al.  Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Fasching,et al.  Previous episodes of hypoglycemic coma are not associated with permanent cognitive brain dysfunction in IDDM patients on intensive insulin treatment. , 1998, Diabetes.

[10]  M. A. Viergever,et al.  Automated measurement of brain and white matter lesion volume in type 2 diabetes mellitus , 2007, Diabetologia.

[11]  C. Stam,et al.  Phase lag index: Assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources , 2007, Human brain mapping.

[12]  G. Reaven,et al.  Verbal Learning and/or Memory Improves with Glycemic Control in Older Subjects with Non‐Insulin‐Dependent Diabetes Mellitus , 1993, Journal of the American Geriatrics Society.

[13]  G. Reaven,et al.  Relationship Between Hyperglycemia and Cognitive Function in Older NIDDM Patients , 1990, Diabetes Care.

[14]  E. Nilsson,et al.  Cognitive performance in very old diabetic persons: the impact of semantic structure, preclinical dementia, and impending death. , 2002, Neuropsychology.

[15]  P. Tun,et al.  Memory self-assessment and performance in aged diabetics and non-diabetics. , 1987, Experimental aging research.

[16]  Elizabeth R Seaquist,et al.  Cognitive Dysfunction and Diabetes Mellitus , 2022 .

[17]  R. Jarrett Type 2 (non-insulin-dependent) diabetes mellitus and coronary heart disease — chicken, egg or neither? , 1984, Diabetologia.

[18]  J. Manson,et al.  Type 2 diabetes and cognitive function in community-dwelling elderly women. , 2001, Diabetes care.

[19]  C. Messier Impact of impaired glucose tolerance and type 2 diabetes on cognitive aging , 2005, Neurobiology of Aging.

[20]  H. Tuokko,et al.  The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. , 1993, Journal of gerontology.

[21]  Vadim V. Nikulin,et al.  Time course and variability of power in different frequency bands of EEG during resting conditions , 2004, Neurophysiologie Clinique/Clinical Neurophysiology.

[22]  D. Singer,et al.  Decreased cognitive function in aging non-insulin-dependent diabetic patients. , 1984, The American journal of medicine.

[23]  K. Hall,et al.  Cross-reaction of serum somatomedin-binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid. , 1984, Acta endocrinologica.

[24]  J. Polich,et al.  P300 and Alzheimer's disease: oddball task difficulty and modality effects. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[25]  J. Gillis,et al.  Classical dynamics of particles and systems , 1965 .

[26]  F. Barkhof,et al.  Cognitive performance in type 1 diabetes patients is associated with cerebral white matter volume , 2007, Diabetologia.

[27]  (On the Occasion of His 70th Birthday) , 2002 .

[28]  T. Brismar,et al.  Predictors of cognitive impairment in type 1 diabetes , 2007, Psychoneuroendocrinology.

[29]  T. Brismar,et al.  Cognitive impairment correlates to low auditory event-related potential amplitudes in type 1 diabetes , 2008, Psychoneuroendocrinology.

[30]  D. Andrewes,et al.  Neuropsychological Complications of IDDM in Children 2 Years After Disease Onset , 1998, Diabetes Care.

[31]  L. Bäckman,et al.  Episodic memory functioning in a community-based sample of old adults with major depression: utilization of cognitive support. , 1994, Journal of abnormal psychology.

[32]  F. Rist,et al.  Effects of improved glycaemic control maintained for 3 months on cognitive function in patients with Type 2 diabetes , 2004, Diabetic medicine : a journal of the British Diabetic Association.

[33]  K. Sleegers,et al.  Cholesterol and triglycerides moderate the effect of apolipoprotein E on memory functioning in older adults. , 2007, The journals of gerontology. Series B, Psychological sciences and social sciences.

[34]  T. Brismar,et al.  Loss of temporal lobe beta power in young adults with type 1 diabetes mellitus , 2002, Neuroreport.

[35]  B. Mueller,et al.  Diffusion Tensor Imaging Identifies Deficits in White Matter Microstructure in Subjects With Type 1 Diabetes That Correlate With Reduced Neurocognitive Function , 2008, Diabetes.

[36]  J. Martinerie,et al.  The brainweb: Phase synchronization and large-scale integration , 2001, Nature Reviews Neuroscience.

[37]  C. Stam,et al.  Functional Brain Connectivity and Neurocognitive Functioning in Patients With Long-Standing Type 1 Diabetes With and Without Microvascular Complications , 2009, Diabetes.

[38]  Nick Bryan,et al.  Clinical Correlates of Ventricular and Sulcal Size on Cranial Magnetic Resonance Imaging of 3,301 Elderly People , 1999, Neuroepidemiology.

[39]  K. Perryman,et al.  Cortical function in elderly non-insulin dependent diabetic patients. Behavioral and electrophysiologic studies. , 1988, Archives of internal medicine.

[40]  T. Orchard,et al.  Psychomotor Slowing Is Associated With Distal Symmetrical Polyneuropathy in Adults With Diabetes Mellitus , 1992, Diabetes.

[41]  T. Brismar,et al.  EEG abnormalities with and without relation to severe hypoglycaemia in adolescents with type 1 diabetes , 2005, Diabetologia.

[42]  I. Deary,et al.  Is Type II Diabetes Associated With an Increased Risk of Cognitive Dysfunction?: A critical review of published studies , 1997, Diabetes Care.

[43]  K. Højlund,et al.  Development and clinical evaluation of a novel immunoassay for the binary complex of IGF-I and IGF-binding protein-1 in human serum. , 2002, The Journal of clinical endocrinology and metabolism.

[44]  Carole Dufouil,et al.  Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study. , 2004, Diabetes.

[45]  A. Kurita,et al.  Neurophysiological evidence for altered higher brain functions in NIDDM. , 1996 .

[46]  G. Pozzessere,et al.  Abnormalities of Cognitive Functions in IDDM Revealed by P300 Event-Related Potential Analysis: Comparison With Short-Latency Evoked Potentials and Psychometric Tests , 1991, Diabetes.

[47]  K Yaffe,et al.  Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. , 2000, Archives of internal medicine.

[48]  Geert Jan Biessels,et al.  Brain Imaging in Patients With Diabetes , 2006, Diabetes Care.