DM and Neurology Copy

8/22/2019 DM and Neurology Copy

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Cross talk:

Neuro logy and Diabetes

Surat Tanprawate, MD, MSc(Lond.), FRCP(T)

The Northern Neuroscience Center in

Collaboration with Division of Neurology

Chiang Mai University


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A disease with symptoms such asconstant thirst (polydipsia),excessive urination (polyuria) andloss of weight.

He named the conditiondiabetes, meaninga flowing through.

Aretaeus, Greekphysician

(30-90CE)

Early desc r ipt ion o f Diabetes


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Major complication of Diabetes

Cardiovascular complication

Non-cardiovascular complication

Kannel WB, McGee DL. JAMA 1979;241:2035-8

Nephropathy

Neuropathy

Diabetic foot

Stroke


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Neuro logica l compl icat ion of

diabetes

CNS: Cerebrovascular disease,

Dementia

PNS: Neuropathies of diabetes->

diabetic foot


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Stroke and Diabetes

- Risk factor of stroke

- Outcome after stroke


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Diabetes and Stroke

DiabetesMicro- and

macrovascular

change

AtherosclerosisIschemic

st roke

Coronary heart

disease, cardiac

arrhythmia

Arterial

hypertension

Relative risk 1.8-6 fold of

stroke in DM


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Risk factor of stroke fatality

Steven RJ, et al. Diabetes Care 2004;27:201-07

**

**


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4537 patients hospitalized fora first-in-a-lifetime strokeTo examine the relationshipbetween diabetes and outcomeat 3 months (disability,

handicap, and death),controlling for risk factors,clinical presentation, anddemographics.

Diabet ic pat ients are more l ikely to have...limb weakness (P< 0.02)...dysarthria (P< 0.001)...ischemic stroke (P< 0.001)

...lacunar cerebral infarction (P< 0.03)

At 3 months,...the case fatality rates were not higher in thediabetic groups (P0.33)....Handicap (Rankin Scale) and disability

(Barthel Index) were significantly higher indiabetic patients (P< 0.005 and P< 0.016,

respectively).Megnerbi SE et al. Stroke 2003;34;688-694


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The Most successful treatment instroke is to prevent stroke !


11/43Stroke 2011;42;517-584


12/43DIABETES CARE, VOLUME 36, SUPPLEMENT 1, JANUARY 2013 S11


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Aggregate Clinical Endpoints

ukpds

1977-1991: Type 2 DM 5102 patients;

conventional (


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Primary p revent ion of s troke

UKPDS: conventional (


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Conclusion: stroke primary

prevention in diabetes There is no evidence that reduced glycemia

decreases short-term risk of macrovascular

events, including stroke, in patients with type 2

diabetes.

A glycohemoglobin goal of 7.0% has beenrecommended by the ADA to prevent long-term

microangiopathic complications in patients withtype 2 diabetes.

Whether control to this level also reduces thelong-term risk of cardiovascular events and

stroke requires further study. Stroke 2011;42;517-584


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Stroke 2011;42;227-276


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Secondary p revent ion of stroke

ACCORD: pt. with type 2 DM and vascular disease (intensive

vs conventional)

There was no significant difference in the rate of nonfatal

stroke

ADVANCE: pt. with type 2 DM and history of macrovascular

disease(9% stroke)

There was no significant reduction in the occurrence of

nonfatal stroke

Stroke 2011;42;517-584


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Why does glycemic control fail to prevent

Cerebrovascular disease?

Hypoglycemic event

Glycemic variability


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Actual Therapy analysis

ukpds

The UK Prospective Diabetes Study (UKPDS)

Hypoglycemic episode per annum

Conventional therapy

Intensive therapy

Intensive therapy

Conventional therapy


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Mechanisms by which hypoglycemia may affect cardiovascular events

Desouza C V et al. Dia Care 2010;33:1389-1394

Copyright 2011 American Diabetes Association, Inc.


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21

Graphic representations of glycemic control with high

(a) or low (b) variability.

patients with similar

glycosylated hemoglobin

levels and mean glucose

values can have markedlydifferent daily glucose

excursions

Egi, M., Bellomo, R., & Reade, M. C. (2009). Is reducing variability of

blood glucose the real but hidden target of intensive insulin therapy?.Critical Care, 13(2), 302.


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22

Correlation between carotid IMT and glycemic variability

in subjects without atherosclerotic lesion on MRA

Mo, Y., Zhou, J., Li, M., Wang, Y., Bao, Y., Ma, X., ... & Jia, W. (2013). Glycemic variability is associated with subclinical atherosclerosis

in Chinese type 2 diabetic patients. Cardiovascular diabetology, 12(1), 1-9.


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23Barbieri, M., Rizzo, M. R., Marfella, R., Boccardi, V., Esposito, A., Pansini, A., & Paolisso, G. (2013). Decreased carotid atheroscleroticprocess by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors.Atherosclerosis.

* p< 0.05 vs baseline ; + p


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PROactive: pt. with DM and macrovascular disease

using pioglitazone


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http://www.iristrial.org

The Insul in Resist ance Interventio n after Stroke (IRIS) trialis an

ongoing study funded by the National Institute for Neurological Disorders

and Stroke (NINDS)in which patients with TIA or stro keare randomly

assigned to piogl i tazoneor placebo for a primary outcome of stroke and MI
http://www.iristrial.org/http://www.iristrial.org/


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Conc lusion : diabetes and s troke

The incidence of stroke is high among diabetics

The severity of ischemic stroke and death are

increased with DM

We are waiting for the evidence of glycemic control

to prevent stroke


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Neuropathy o f Diabetes


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Definition

Diabetic neuropathy is defined as

The presence of symptoms and signs of peripheral nerve dysfunction in

individuals with diabetes after the exclusion of other causes.

CIDP, vitamin B12 deficiency, alcoholicneuropathy, endocrine neuropathy


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The riskof developing symptomatic

neuropathy in patients without

neuropathic symptoms or signs at thetime of initial diagnosis of diabetes is

estimated to be

4% to 10% by 5 years

50% by 25 years


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Clin ical Pattern o f Diabet ic neuropathy

- Distal sensory or

sensorimotor

polyneuropathy (DSDP)-

Small-fiber neuropathy

Cranial neuropathy

Truncal neuropathy

Mononeuropathy/multiple

mononeuropathyRadiculoneuropathy

3/4 of all

cases

- Diabetic Autonomic Neuropathy (DAN)

- Diabetic amyotrophy


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Major complication of Diabetic

neuropathy

Charcots joint

Foot ulcer

Picture from Br J Sports Med2003;37:3035


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5

10

15

20

25

6.9-9.2 9.3-10.8 10.9-12.6 12.7-23.6

Ulcers and amputations

Odds ratio 1.6 for each absolute increment in A1C of 2%

Moss SE et al.Arch Intern Med. 1992;152:610-616.

Risk of Foot Complications and

Glycemia in Older-Onset Diabetes

Patients (WESDR)


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Microfilament testing

Rith-Najarian SJ et al. Diabetes Care.1992;15:1386-1389


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Management

Prevention

Pathogenetic treatment

Symptomatic treatment


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DCCT: Result Summary

Improved control of blood glucose reduces the risk of clinically

meaningful

Retinopathy 76% (P


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Clinical trials investigating effects of enhanced glucose

control on neuropathy

Lancet Neurol 2012; 11: 52134


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Proposed pathophysiology


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Pathogenetic treatmen t


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Symptomat ic treatment

Pain control

TACs, antiepileptic drugs, opioid like drug

Treatment in dysautonomic symptom

gastrointestinal, sexual dysfunction, cardiac

symptom


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Conclusion : diabetes and neuropathy

The incidence of neuropathy and its complication

are highly disable

Glycemic control can prevent diabetic neuropathy


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reduced cognitive performance, in particular

slowing of information processing speed


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Thank you foryour attention


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Mechanisms by whichhyperglycaemia and diabetes

may influence cellularischaemia

Impair cerebral autoregulation

Higher rate of stroke recurrence

Higher rate of atherosclerotic risk

Cause

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DM and Neurology Copy