diabetic autonomic neuropathy (dan). introduction
TRANSCRIPT
Diabetic AutonomicNeuropathy
(DAN)
Introduction
Epidemi0logy● Is a serious & a common complication of DM .● Frequently coexists with other peripheral neuropathies & other diabetic complications or may be isolated .● Frequently precedes the detection of other complications .● Prevalence of DAN varies depending on : 1)whether studies have been carried out in the community , clinic , or tertiary referral center . 2)lack of standard accepted definition of DAN & different diagnostic methods . 3)age , sex , duration of DM , type of DM & glycemic control . ● The 5 year mortality rate of diabetics who showed symptoms of DAN & a disrupted HRV in cardiovascular autonomic function tests was 53% , compared to only 15% in diabetics without autonomic dysfunction .
Clinical manifestationsCardiovascular :- Gastrointestinal:- Resting tachycardia Esophageal dysmotility Orthostatic hypotension Constipation Exercise intolerance Diarrhea Silent myocardial ischemia Fecal incontinenceGenitourinary:- Metabolic:- Neurogenic bladder Hypoglycemic unawareness Erectile dysfunction Hypoglycemia - associated Retrograde ejaculation autonomic failure Dyspareunia Sudomotor:- Pupillary:- Anhydrosis & dry skin Decrease diameter of dark - Heat intolereance adapted pupil
Differential Diagnosis
(1)Pure autonomic failure (formerly called idiopathic orthostatic hypotension) (2)Multiple system atrophy with autonomic failure (formerly called Shy - Drager syndrome)(3)Addison’s disease & hypopituitarism (4)Hypovolemia (5)Peripheral autonomic neuropathies (e.g amyloid neuropathy , idiopathic autonomic neuropathy)(6)Medications (e.g sympathetic blockers , vasodilators )
Pathophysiology
Possible pathological mechanisms of diabetic neuropathy :
● Disorders of polyol metabolism ● Disorders of FA metabolism ● Accumulation of glycated proteins● Endoneural ischemia ● Oxidative stress ● Destruction of nerve growth factors & axonal transport ● Immunological : autoimmune , inflammatory response
Aim of the work
To study autonomic changes that accompany diabetic neuropathy
Materials & Methods
The tests were done on 2 groups :
Control group (n=2) : Known healthy subjects
Diabetic neuropathy group (n=2) : Known diabetic patients complicated with peripheral neuropathy
Power lab apparatus
SphygmomanometerBridge amplifier
Bio amplifier
Pneumotracer
ECG leads
Disposable syringe
Hand grip
Screening (A)Parasympathetic tests :- HR response to deep breathing :-
- The patient breathes deeply for 3 cycles . - Greatest HR difference during each cycle is measured & the differences are averaged . Normal : ≥ 15 BPM Borderline : 11-14 BPM Abnormal : ≤ 10 BPM
First cycle
Second cycle
Third cycle
Average HR
Control 1
96 - 80 = 16
96 - 79 = 17
97 - 97 = 18
17 BPM
Control 2
89 - 59 = 30
87 - 60 = 27
89 - 60 = 29
29 BPM
Patient 1
97 - 89 = 8
88 - 79 = 9
97 - 89 = 8
8 BPM (abnormal)
Patient 2
118 - 90 = 28
135 - 94 = 41
139 - 77 = 62
44 BPM
HRV with deep respiration (Control)
HRV with deep respiration (Patients)
HR response to Valsalva :- - Subject breathes into disposable cardboard
mouthpiece attached to sphygmomanometer to keep
pressure at 40 mmHg for 15 sec .- Ratio of longest R-R within 20 beats of
ending manouvre to shortest R-R during manouvre .- Test is done 3 times & the average ratio is
measured .
Normal : ≥ 1.21 Abnormal : ≤ 1.20
First Valsalva
Second Valsalva
Third Valsalva
Average ratio
Control 1
0.88 s/0.56 s = 1.58
0.89 s/0.56 s = 1.6
0.89 s/0.56 s = 1.6
1.59
Control 2
0.78 s/0.35 s = 2.21
0.76 s/0.54 s = 1.40
0.98 s/o.30 s = 3.21
2.27
Patient 1
1.22 s/0.52 s = 2.33
0.84 s/0.52 s = 1.6
1 s/ 0.5 s = 2
1.97
Patient 2
0.92 s/0.27 s = 3.55
0.63 s/0.17 s = 3.69
1.01 s/0.23 s = 4.44
3.89
HR response to Valsalva (Control)
HR response to Valsalva (Patients)
HR response to standing :- 30 : 15 ratio Longest R-R at 30th beat & Shortest R-R at 15th beat Normal : ≥ 1.04 Borderline : 1.01-1.04 Abnormal : ≤ 1.00
Shortest R-R Longest R-R 30 : 15 ratio
Control 1 0.05 s 0.26 s 5.57
Control 2 0.272 s 0.89 s 3.27
Patient 1 0.24 s 0.3 s 1.24
Patient 2 0.35 s 1.28 s 3.67
B)Sympathetic tests :- BP response to standing :-
Normal : ≤ 10 mmHg Borderline : 11-20 mmHg Abnormal : ≥ 30 mmHg
Lying Standing
(after 1 min)
Difference in
systolic BP
Control 1 120 / 80 120 / 80 zero
Control 2 120 / 75 130 / 80 10
Patient 1 140 / 90 140 / 90 zero
Patient 2 100 / 70 88 / 70 12 (Borderline)
Response to standing (Control)
Response to standing (Patients)
BP response to sustained handgrip :-
- Maintaining handgrip at 30% of max. voluntary pressure for up to 5 min .- Systolic BP is recorded every min . - Stop if rise reaches normal level . If not , record just before handgrip release at 5 min .
Normal : ≥ 16 mmHg Borderline : 11-15 mmHg Abnormal : ≤ 10 mmHg
Before
1 min
2 min
3 min
4 min
5 min
Control 1
120 / 80
130 / 90
130 / 96
136 / 98
Control 2
130 / 90
140 / 90
144 / 100
146 / 100
Patient 1
140 / 100
142 / 108
150 / 100
140 / 110
140 / 106
140 / 106(abnormal)
Patient 2
100 / 80
110 / 90
114 / 90
116 / 90
Hand grip (Control + patients)
Discussion
► The tests described are based on the responses of HR & BP to variety of stimuli . ► The first 3 tests reflect cardiac parasympathetic integrity . While the last 2 tests start to give abnormal results with more severe sympathetic nerve damage . ► While each test may be used individually , all 5 should be performed when possible , so giving fuller information about the state of the autonomic nervous system . ► These tests are valid as specific markers of autonomic neuropathy if the following has been carefully ruled out & taken into consideration : 1-End-organ failure & other concomitant illness 2-Drug use (including anti-depressants , over-the-counter antihistaminics & cough , cold preparations , diuretics & aspirin) 3-Life style issues (such as exercise , smoking & caffeine intake) 4-Age
GradingNormal : All tests normal or 1 borderline
Mildly abnormal : One of the 3 HR tests abnormal or 2 borderline
Definitely abnormal : ≥ 2 of the HR tests abnormal
Severely abnormal : ≥ 2 of the HR tests abnormal plus one or both of the BP tests abnormal , or both borderline EWING DJ, CLARKE BF (1982):Diagnosis and management of diabetic autonomic neuropathy. BRITISH MEDICAL JOURNAL; 285 2 OCTOBER :916-18.
► By studying the results of the control group & the diabetic neuropathy group , we found that :
- HRV with deep respiration was below the normal level in patient 1 while it was normal in patient 2 . -There was no abnormality detected in results of Valsalva test & HR response to standing in both patients . -The result of BP response to sustained handgrip was below the normal level in patient 1 . -Results of BP response to standing test in patient 2 was borderline .
-To conclude , patient 1 has both sympathetic & parasympathetic affection . On the other hand patient 2 is normal , yet the sympathetic system starts to be affected .
►The natural history of autonomic damage in diabetic patients is becoming clearer , with parasympathetic damage occurring earlier . Ewing DJ, Campbell IW, Clarke BF (1981): Heart rate changes in diabetes Mellitus. Lancet;i:183-6.
However , this isn’t always the fact , sometimes the sympathetic system may be affected earlier than parasympathetic system . (http://care.diabetesjournals.org/content/26/5/1553.full)
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