DIABETES AUTONOMIC
NEUROPATHY
MONICA MORENO MD
ENDOCRINOLOGY AND DIABETES CLINIC
IHC SAINT GEORGE UT
SALT LAKE CITY
NOVEMBER 2 2011
Objectives
• Identify the pathophysiologic mechanisms
and clinical manifestations of diabetic
autonomic neuropathy (DAN).
• Discuss and describe aspects of screening,
prevention and education for patients at risk
for DAN.
Diabetic Neuropathy
• Involvement of peripheral and autonomic
nervous systems
• Most common complication of diabetes
• Underdiagnosed and Undertreated
• Substantial morbidity/mortality (CAN)
Diabetic neuropathy
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Distal symmetric polyneuropathy
Focal Mononeuropathies
Autonomic neuropathy
Polyradiculopathies
Mononeuropathy multiple
DIABETIC AUTONOMIC
NEUROPATHY (DAN)
• Least recognized and
understood complications of
diabetes.
• Can involve the entire
autonomic nervous system
(ANS)
• May be either clinically
evident or subclinical
DAN: Incidence
Panbianco et Al. The pittsburgh Epidemiology
of Diabetes Complications Study experience
DAN: Prevalence
Tesfaye et Al. Vascular Risk Factors and Diabetic Neuropathy.
EURODIAB Prospective Complication Study Group NEJM 352;4
January 27, 2005
Pathophysiology
Vinik A: Diabetic Neuropathy: Pathogenesis and Therapy. Am J Med 107
(2B):17S-26S, 1999
DAN: Risk Factors
Tesfaye et Al. Vascular
Risk Factors and Diabetic
Neuropathy. EURODIAB
Prospective Complication
Study Group NEJM
352;4 January 27, 2005
DAN: Risk Factors
Tesfaye et Al. Vascular
Risk Factors and Diabetic
Neuropathy. EURODIAB
Prospective Complication
Study Group NEJM
352;4 January 27, 2005
Clinical Presentation
• Clinical symptoms generally do not
appear until long after the onset of
diabetes. However, subclinical
autonomic dysfunction can occur within
a year of diagnosis in type 2 diabetes
patients and within two years in type 1
diabetes patients
Pfeifer MA, Weinberg CR, Cook DL, Reenan A, Halter JB,
Ensinck JW: Autonomic neural dysfunction in recently
diagnosed diabetic subjects. Diabetes Care 7:447-453,
1984
Clinical Presentation
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Functional (e.g. gastroparesis with hyperglycemia and ketoacidosis)
Organic (nerve fibers are actually lost)
AN is not unique to diabetes: establish the diagnosis and exclude
other causes.
The best studied methods:evaluation of cardiovascular reflexes (can be
easily done in clinic setting)
This tests can be used as a surrogate for the diagnosis of AN of any
system since it is generally rare to find involvement of any other
division of the ANS in the absence of cardiovascular autonomic
dysfunction
Differential Diagnosis
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Idiopathic Orthostatic hypotension
Panhypopituitarism
Pheochromocytoma
Amyloidosis
Hypovolemia from diuretics
SE from medications
CHF
Hypoglycemia due to intensive glycemic
control.
CAN
• Most studied and clinically important
• Increased CV mortality
• damage to the autonomic nerve fibers
that innervate the heart and blood
vessels, resulting in abnormalities in
heart rate control and vascular
dynamics.4
Relative risks and 95% CIs for studies of cardiovascular neuropathy (CAN) and mortality.
Maser R E et al. Dia Care 2003;26:1895-1901
Copyright © 2011 American Diabetes Association, Inc.
Effects of Cardiac Autonomic Dysfunction on Mortality Risk in the Action to
Control Cardiovascular Risk in Diabetes (ACCORD) Trial. Pop-Busui R et al.
Dia Care 2010;33:1578-1584
Central CAN
1.Tachycardia (HR >100 bpm)
2.Decreased exercise tolerance
3.Orthostasis (>20mmHg fall in systolic BP
upon standing without compensationHR)
4.Cardiac denervation syndrome= SILENT MI
5.Paradoxic supine or nocturnal hypertension
6.Intraoperative and perioperative
cardiovascular instability
7. Left ventricular diastolic dysfunction
Peripheral CAN
1. Decreased thermoregulation
2. Decreased sweating
3. Altered blood flow
4. Impaired vasomotion
5. Edema
Testing for CAN
Testing for CAN
METABOLIC
1.Hypoglycemia unawareness: decreased
counterregulatory catecholamine
responses
2.Hypoglycemia unresponsiveness:
Reduction in glucagon and epinephrine
secretion in response to Hypoglycemia
GI
• Esophageal dysmotility
• Gastroparesis diabeticorum (25%)
• Diarrhea (20% nocturnal diarrhea/fecal
incontinence)
• Constipation (60%)
• Fecal incontinence
GU
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Erectile dysfunction (50% at 10 years)
Retrograde ejaculation
Neurogenic bladder and cystopathy
Female sexual dysfunction (20% loss
of vaginal lubrication)
Sudomotor
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Anhidrosis
Hyperhidrosis
Heat intolerance
Gustatory sweating
Dry skin
Pupillary
1. Pupillomotor function impairment (e.g.,
decreased diameter of dark adapted
pupil)
2. Pseudo Argyll-Robertson pupil
DAN Screening
ADA Guidelines 2011
• At the time of diagnosis DM2
• 5 years after diagnosis DM1
• Special testing rarely needed, may not affect
management or outcomes
DAN Screening
ADA Guidelines 2011
• Increase risk of exercise induce injury or
adverse event
• Patients should undergo cardiac investigation
before intensifying physical activity
DAN Screening
ADA Guidelines 2011
• Comprehensive HPI
• Microvascular complications:
–
–
DPN
DAN (ED,gastroparesis, incontinence,
recurrent infections, hypogycemia
unawareness)
DAN Screening
ADA Guidelines 2011
• Signs: tachycardia, orthostatic hypotension,
abnormal monofilament or VPT testing
• Test HR variability
E:I ratio, valsalva maneuver, standing, EKG
• If normal repeat once a year
DAN treatment
• !!Prevention!!
• Once stablished: Improve glycemic control
can slow progression but not reversal of
neuronal loss if advanced at time of
diagnoses.
• Symptomatic treatment: can improve quality
of life of the patient.
DAN treatment
Gaede et Al. Multifactorial Intervention and Cardiovascular disease in Patients with
Type 2 Diabetes. Steno 2 Trial. N Engl J Med 2003;348:383-93
CAN
• Nuclear Stress test
• ACE I, BB, Antioxidants (Alpha-lipoic acid)
• Supportive garments for orthostatic
hypotension
• Clonidine, fludrocortisone, midodrine,
octreotide?
Gastroparesis
• Suspect if erratic glucose control or upper GI
symptoms without other identified cause
• Gastric emptying study, barium study,
Endoscopy : poorly correlation with
symptoms.
• Diet, prokinetic agents, bulking agents
GU
• ED: therapy, phosphodiesterase type 5
inhibitors, intracorporeal or intraurethral
prostaglandins, vacuum devices, or penile
prostheses.
• Bladder: Postvoidal residual: bethanechol,
intermitent catheterization
Hypoglycemia
• Avoidance of recurrent hypoglycemia
• Frequent FSBG testing or CMGS
• Individualized HgA1c goals
CGMS
CGMS