Download - DPP-4 Inhibitor and the Brain
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DPP-4 inhibitor and the Brain
Surat Tanprawate, MD, MSc(Lond.), FRCP(T)1, 2 1Division of Neurology, Department of Medicine
2The Northern Neuroscience Centre Chiang Mai University
NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
Issue of DM and the Brain Neurological complication of Diabetes and
guideline recommendation
Real life practice
New insight and future trends
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Neurological of Diabetes and Guideline recommendation
What guideline guides us?
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DM complicatio
nRisk
Trials of glycemic control to prevent
strokeResult from
the trialRecommendation from ASA stroke guideline (2014)
First stroke
- DM double risk of stroke
- DM may be responsible for >8% of first ischemic stroke
- 20% of DM pt. will die of stroke
- DM is RR for the first stroke -> 1.5-3.7
UKPDS (diet restriction vs intensive therapy)
ACCORD (intensive Rx HbA1c
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
DDP-4 inhibitor, glycemic control and stroke prevention
No major study available
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
Diabetic neuropathy Diabetic neuropathies are heterogenous with diverse clinical
manifestation (focal vs diffuse) : Most common forms: DPN, and autonomic neuropathy
Risk Trials of glycemic control to prevent DPNResult from the
trial Recommendation
DPN4% to 10% by 5 years
50% by 25 years
DCCT/EDIC research trial - in DM type 1
ACCORD trial: Intensive blood glucose control and vascular outcome
Cochrane Rev
Glycemic control was shown to effectively prevent DPN and CAN in type I DM
Glycemic control may modestly slow progression in type 2 DM
Tight glycemic control implement early in the course of DM, has been shown to effectively prevent or delay development of DPN and CAN in DM type 1, but evidence is not strong in DM type 2
Martin CL, et al Diabetes Care 2014;37:3138Patel A, et al. N Engl J Med 2008;358:25602572 Callaghan BC et al. Cochrane Database Syst Rev 2012;6
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
Diabetic neuropathy, glycemic control with DPP-4 inhibitor
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Real life practiceWhat we concern?
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
The studies on hypoglycaemic event related to cognitive impairment
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group; Jacobson AM, Musen G, Ryan CM, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007;356:1842-1852.
Punthakee Z, et al.ACCORD Group of Investigators: ACCORD-MIND Investigators. Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care. 2012;35(4):787-93.
Aung PP, et al. Edinburgh Type2 Diabetes Study Investigators. Severe hypoglycaemia and late-life cognitive ability in older people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabet Med. 2012;29:328-336.
Whitmer RA et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA. 2009;301:1565-1572.
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
Association between hypoglycaemia and dementia in biracial cohort of older adult with DMYaffe K. et al. JAMA Intern Med. 2013 July 22; 173(14)
783 older adult with DM, 12 years F/U period, severe hypoglycaemic episode with cognitive assessment record
61 participants (7.8%) had a reported hypoglycemic event
148 (18.9%) developed dementia
Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia
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NNC CMUThe Northern Neuroscience Centre
Chiang Mai University
Hyperglycemia and glycemic fluctuations
Oxidative stress Advanced glycation end-products
Endothelial dysfunction Cerebral hyperosmolarity
Microangiopathy Macroangiopathy
HT and Dyslipidemia
Cognitive disorders
DementiaInflammation
GeneticsAge
Insulin resistanceInsulin can regulate
phosphorylation of tau protein and clearance of
amyloid protein
Hypoglycemia
Buysschaert M et al. Medecine Maladies Mtaboliques 2015;9:47-52
Cognitive impairment in Diabetes
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New insight and Future trends
Diabetes & Dementia: how sweet we are?
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Craft, S. (2007). Curr Alzheimer Res 4, 147-52.
IDE, Insulin degrading enzyme FFA, Free fatty acid
peripheral hyperinsulinemia decrease insulin transport into the CNS
Long term increase can transport into the brain
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Slaked I et al. British Journal of Pharmacology (2012) 166 15861599
GLP-1 : an emerging opportunity to treat neurodegenerative disease
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Hiranya Pintana, Nattayaporn Apaijai, Nipon Chattipakorn and Siriporn C Chattipakorn from Chiang Mai University Journal of Endocrinology 218.1 (2013): 1-11.
DPP-4 Inhibitors improve cognition and brain mitochondrial function of insulin resistant in Rat
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J Diabetes Investig 2015