Type 2 Diabetes Mellitus and CNS

Transcription

1 Type 2 Diabetes Mellitus and CNS Grigorios Nasios, MD, Ph.D Neurologist, Associate Professor, TEI of Epirus, Department of Speech and Language Therapy, Ioannina, Greece nasios@ioa.teiep.gr 1

2 Whenever You Lose Concentration, Take Intranasal Insulin? Antje Gottschalk and Bjo rn Ellger Diabetes 2015 Mar; 64(3):

3 Intranasal Insulin Boosts Cognitive Function Shemesh E, Rudich A, Harman-Boehm I, Cukierman-Yaffe T. J Clin Endocrinol Metab Feb;97(2): Effect of intranasal insulin on cognitive function: a systematic review. 3

4 Intranasal Insulin Enhanced Resting- State Functional Connectivity of Hippocampal Regions in Type 2 Diabetes Hui Zhang et al. Diabetes 2015 Mar; 64(3): Conference on Neurodegenerative 4

5 We are talking about the diabetic brain! 5

6 TALK S OUTLINE 1. Type 2 DM: A multi-organ epidemic disease 1. T2DM and the Brain 1. Mechanisms underlying altered cognition 1. T2DM and Alzheimer s dementia 1. Concluding remarks 6

7 World Health Organization s 2016 Global report on Diabetes 1. The number of people with diabetes has risen from 108 million in 1980 to 422 million in The global prevalence of diabetes among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. 1. Almost half of all deaths attributable to high blood glucose occur before the age of 70 years. WHO projects that diabetes will be the 7th leading cause of death in Conference on Neurodegenerative 7

8 Diabetes Mellitus Type 2 (T2DM) - I Occurs due to insulin resistance or insensitivity of tissues to insulin and relative insulin deficiency. Obesity is a major risk factor. Decreased entry of glucose into insulinsensitive cells and increased release of glucose from the liver leads to hyperglycemia. 8

9 Diabetes Mellitus Type 2 (T2DM) - II Complications are related to both duration of diabetes and uncontrolled plasma glucose levels. Heritability is high (estimated to be > 50%) and provides evidence to the genetic risk associated. High calorie food intake, lack of physical activity, sleep deprivation, and low socioeconomic status seem to play important role. 9

10 DM type 2 : A multi-organ epidemic disease T2DM affects most body s systems and organs, among them more importantly : endocrine system (pancreas, liver, visceral fat) circulatory system (heart, large and small vessels, hypertension, elevated lipid levels) nervous system (brain, eyes, ears, nerves) urinary system (Kidneys, bladder) immune system (bone marrow, white blood cells) myoskeletal system (muscles, bones, the feet) digestive system (intenstine) reproductive system 10

11 TALK S OUTLINE 1. Type 2 DM: A multi-organ epidemic disease 1. T2DM and the Brain 1. Mechanisms underlying altered cognition 1. T2DM and Alzheimer s dementia 1. Concluding remarks 11

12 Relationship Between Hyperglycemia and Cognitive Function in Older NIDDM Patients. Diabetes Care 1990 Jan; 13(1): Gerald M Reaven, et. al. 1. Measures of verbal learning, abstract reasoning, and complex psychomotor functioning were performed more poorly by diabetic than nondiabetic subjects. 2. Within the diabetic group, individuals with poorer metabolic control performed more poorly on tasks involving learning, reasoning, and complex psychomotor performance, although this relationship was not evident for simple verbal or motor tasks. Conference on Neurodegenerative 12

13 Neurophysiological evidence for altered higher brain functions in NIDDM. Diabetes Care Apr;19(4): Kurita A, Katayama K, Mochio S. 1. Auditory P300 event-related potentials were recorded in 60 NIDDM patients who had no evidence of stroke, dementia, or any other neurological illnesses. 1. Diabetic patients had significantly longer P300 latencies than control subjects. 1. There was a trend toward longer P300 latencies in diabetic patients with retinopathy and in those with HbA1 of > or = 10%. 1. Microangiopathy and metabolic derangement may contribute to the pathophysiology of central nervous system involvement. 13

14 T2DM alters brain s structure and functions - I 1. Hippocampus and parahippocampal gyrus may be particularly vulnerable to the deleterious effects of T2DM. (J Clin Exp Neuropsychol. 2014;36(1):74-87). 1. T2DM has been related to diminished cerebral blood flow and cerebrovascular reactivity, particularly in more advanced disease. (Eur Neuropsychopharmacol Dec;24(12): ). 1. Impaired cerebral perfusion during mental tasks is accompanied by poor cognitive performance and stiffness in the cerebral vessels. (J Diabetes Complications Jun 30. pii: S (16) ). 1. Microangiopathy and metabolic derangement may contribute to the pathophysiology of central nervous system involvement. 14

15 T2DM alters brain s structure and functions - II 5. Declines of gray matter volume, cortical thickness, and surface area were found in T2DM patients. (Neurosci Lett Oct 8;606:100-5). 6. Markers of cortical atrophy and white matter lesion volume are associated with cognitive function in African Americans with type 2 diabetes. (AJNR Am J Neuroradiol Sep;36(9): ). 7. Patients with T2DM had lower total gray, white, and hippocampal volumes. Regions with loss of gray matter include the medial temporal, anterior cingulate, and medial frontal lobes. White matter loss was found in the frontal and temporal regions. (Diabetes Care 2013 Dec; 36(12): ). 8. Using diffusion MRI microstructural abnormalities and disruptions in the white matter network were found in individuals with T2DM compared with controls. (Diab. Care 2013;36: ). Conference on Neurodegenerative 15

16 TALK S OUTLINE 1. Type 2 DM: A multi-organ epidemic disease 1. T2DM and the Brain 1. Mechanisms underlying altered cognition 1. T2DM and Alzheimer s dementia 1. Concluding remarks 16

17 Mechanisms underlying altered cognition in T2DM T2DM is usually diagnosed at an older age and is commonly associated with obesity, insulin resistance, hypertension, and dyslipidemia, all of which can have a negative impact on the brain. Important role play : 1. imperfect glycaemic control 1. microvascular complications age comorbidity 17

18 Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning Medicine (Baltimore) Sep;95(36):e4803. Van Bussel FC, et. al. 1. Insulin signaling plays an important role in synaptic plasticity by modulating neurotransmitter channel activity, including excitatory, and inhibitory receptors. (Diabetes Jul;63(7): ). 1. Defects in brain insulin signaling may give rise to neuronal dysfunction and impaired cognitive performance. (Diabetes Care Sep;36(9): ). 1. Proton MR spectroscopy (1H-MRS) provides the unique opportunity to assess noninvasively the concentrations of neurometabolites in vivo. 1. Participants with type 2 diabetes have alterations in the GABAergic neurotransmitter system, which are related to lower cognitive functioning, and hint at the involvement of an underlying metabolic mechanism. 18

19 T2DM and Alzheimer s dementia - I 1. Both diseases share several common abnormalities. 2. Both diseases disrupt common cellular and molecular pathways and 3. Each disease potentiates the progression of the other. Correia SC et al. : Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res Mar 2;1441:

20 T2DM and Alzheimer s dementia - II Both diseases are characterized by : 1. impaired glucose metabolism, 1. increased oxidative stress, 1. insulin resistance and 1. deposition of amyloidogenic proteins. Correia SC et al. : Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res Mar 2;1441: Conference on Neurodegenerative 20

21 Diabetes Mellitus Induces Alzheimer s Disease Pathology: Histopathological Evidence from Animal Models Nobuyuki Kimura Int. J. Mol. Sci. 2016, 17(4), 503; doi: /ijms

22 because the fundamental abnormalities in AD represent effects of brain insulin resistance and deficiency, and the molecular and biochemical consequences overlap with type 1 and Type 2 diabetes, we suggest the term Type 3 diabetes to account for the underlying abnormalities associated with ADtype neurodegeneration. Type 3 Diabetes is Sporadic Alzheimer s disease: Mini-Review Eur Neuropsychopharmacol Dec; 24(12): Suzanne M. de la Monte 22

23 Programs that promote dietary change and physical activity are effective in reducing the likelihood that people at risk of developing type 2 diabetes will do so. Diet and exercise are effective in preventing type 2 diabetes, task force finds BMJ 2015;351:h3785 Michael McCarthry Conference on Neurodegenerative 23

24 A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia. Mortby ME, Janke AL, Anstey KJ, Sachdev PS, Cherbuin N. PLoS One Sep 4;8(9):e High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study. 24

25 TALK S OUTLINE 1. Type 2 DM: A multi-organ epidemic disease 1. T2DM and the Brain 1. Mechanisms underlying altered cognition 1. T2DM and Alzheimer s dementia 1. Concluding remarks 25

26 CONCLUDING REMARKS Type 2 diabetes is the new global epidemic and has been associated with high risk for dementia. It is linked with structural and functional changes in the brain which challenge cognition. Dietary change and physical activity are important both to prevent and offer better control of T2DM. Increased awareness about the risk of cognitive impairment in diabetes among medical providers is warranted. 26

27 Thank you very much for your attention! 27