This document discusses diabetic neuropathy, its types, risk factors, pathogenesis, and treatment. Diabetic neuropathies are chronic complications of diabetes that manifest in diverse clinical ways. The most common types are distal symmetric polyneuropathy and diabetic autonomic neuropathies. Tight control of blood sugar levels is the primary treatment approach, though additional therapies show some benefits for neuropathic pain relief and prevention of progression. Overall management of this condition remains challenging as existing nerve damage is largely irreversible.

1. DIABETIC NEUROPATHY
Dr Saumya H Mittal
Neurologist
Sharda Hospital & Health City

2. Courtesy:
http://www.healthywealthyandhappy.co.uk/archives/healthy/anat
omy/the-nervous-system/

3. Courtesy: Medscape

4. DIABETIC NEUROPATHY
 Diabetic neuropathies are serious, chronic
complications of diabetes with diverse clinical
manifestations.
 Identified in patients with
 Prediabetes
 Type 1 diabetes mellitus
 Type 2 diabetes mellitus

5. COMMON RISK FACTORS
 Duration of Diabetes
Mellitus
 4-10% by 5 years / up to
50% by 25 years
 Control of Sugar status
 Low serum insulin
concentration
 Smoking and Alcohol
consumption
 Tobacco use
 induces vasoconstriction
and nerve ischemia
 Age
 Male gender
 Damage to the blood
vessels
 Hyperlipidemia
 Mechanical Injury
 Overweight status
 Genetic susceptibility

7.  Distal symmetric polyneuropathy (DSPN) and
diabetic autonomic neuropathies, particularly
cardiovascular autonomic neuropathy (CAN), are
by far the most prevalent of the DNs.
Courtesy: Bradley’s Neurology

8. GENERALIZED SYMMETRICAL
POLYNEUROPATHIES

9. DISTAL SYMMETRICAL POLYNEUROPATHY
 Most common form of diabetic neuropathies.
 Sensory deficits predominate
 stocking-glove distribution.
 Advanced cases, sensation becomes impaired over the
anterior chest and abdomen, producing a truncal
wedge-shaped area of sensory loss.
 Autonomic symptoms usually correlate with the
severity of the neuropathy.
 Minor motor involvement affecting the distal
muscles of the lower extremities.
 2 major subgroups
 large-fiber variant
 small-fiber variant

10. LARGE FIBER NEUROPATHY
 Presents with
 often asymptomatic, but sensory deficit may be
detected by careful examination
 painless paresthesias beginning at the toes and feet
 impairment of vibration and joint position sense
 diminished muscle stretch reflexes
 In advanced cases, significant ataxia may develop

11. SMALL FIBER NEUROPATHY
 Presents with
 pain of a deep, burning, stinging, aching character,
 spontaneous shooting pains,
 allodynia to light touch,
 often accompanied by autonomic neuropathy.
 Pain and temperature modalities are impaired, with
relative preservation of vibration and joint position
sensation and muscle stretch reflexes.

12. OTHER VARIANTS- DIABETIC
POLYRADICULONEUROPATHY
 Often begins as a distal symmetrical
polyneuropathy
 Later involves proximal segments of the PNS
including multiple lumbosacral roots, thoracic
posterior primary rami, and (less commonly)
cervical myotomes.
 Some of these patients respond to high-dose IVIG
therapy, although a controlled clinical trial has not
yet been completed

13. IMPAIRED GLUCOSE TOLERANCE NEUROPATHY
 It is now clear that peripheral neuropathy can occur
before the onset of clinically diagnosable diabetes
mellitus; this is known as impaired glucose
tolerance neuropathy.
 OGTT.

14. TREATMENT-INDUCED NEUROPATHY
 An acute painful neuropathy (burning pain and
paresthesias) develop in the distal lower extremities
 Precipitated following initiation of treatment of a
diabetic patient with insulin.
 Spontaneous resolution to follow.
 Pathological studies demonstrate active axonal
regeneration, which may act as generators of
spontaneous nerve impulses.

15. HYPERGLYCEMIC NEUROPATHY
 Patients may be newly diagnosed diabetes when
they experience transient pain and paresthesias in
the distal lower extremities.
 The symptoms will usually resolve when the
hyperglycemia is brought under control.

16. DIABETIC NEUROPATHIC CACHEXIA
 Acute and severe painful diabetic neuropathy
associated with precipitous severe weight loss,
depression, insomnia, and impotence in men.
 More common in men with poor glucose control.

17. NEUROPATHIC ARTHROPATHY
 Complication seen in patients with diabetes who
often have foot ulcers and autonomic impairment.
 Tends to involve the small joints in the feet.

18. FOCAL AND ASYMMETRICAL
NEUROPATHIES

19. LIMB MONONEUROPATHY
 Single mononeuropathies are caused by two basic
mechanisms:
 nerve infarction : abrupt onset of pain followed by
variable weakness and atrophy.
 Entrapment: more common than nerve infarctions.
 Because the primary pathological lesion results in
acute axonal degeneration, recovery tends to be
slow.
 The median, ulnar, and fibular nerves are most
commonly affected.
 The reason diabetes predisposes to nerve
entrapment is unknown.

20. CRANIAL MONONEUROPATHIES
 A third nerve palsy is the most common.
 Pupillary sparing, the hallmark of diabetic third-nerve
palsy, results from ischemic infarction of the
centrifascicular oculomotor axons due to diabetic
vasculopathy of the vasa nervorum. The peripherally
located pupillary motor fibers are spared as a result of
collateral circulation from the circumferential arteries.
 With decreasing frequency, the fourth, sixth, and
seventh nerves are also affected.

21. TRUNCAL NEUROPATHY
 Involves T4 - T12 spinal nerve roots.
 Causes pain (burning, stabbing, boring, beltlike pain ) or
dysesthesias in areas of the chest or abdomen.
 affecting either the entire dermatomal distribution of adjacent spinal
nerves or,
 restricted areas limited to the distribution of the dorsal or ventral rami
of spinal nerves.
 Bulging of the abdominal wall as a result of weakness of
abdominal muscles may also occur.
 Contact with clothing can be very unpleasant.
 The onset may be either abrupt or gradual.
 The symptoms may persist for several months before gradual
and spontaneous resolution within 4 to 6 months.
 Focal anhidrosis on the trunk correlating with the area of pain is
detected with the help of the thermoregulatory sweat test.

22. MULTIPLE MONONEUROPATHIES
 Involvement of two or more nerves.
 Onset is abrupt in one nerve, and then other nerves
are involved sequentially at irregular intervals.
 Nerve infarction results from occlusion of the vasa
nervorum.

23. DIABETIC AMYOTROPHY / BRUNS GARLAND
SYNDROME
 This is debilitating, painful,
asymmetrical motor neuropathy with
profound atrophy of proximal leg
muscles.
 Pain usually recedes spontaneously
long before motor strength begins
to improve.
 Involvement of multiple nerve roots
or proximal nerve segments.
 Almost always restricted to the
lower limbs. In some patients,
additional body region is also
affected, mostly the thoracic
occasionally cervical region.

24.  Although a beneficial effect of immunomodulating
therapies has been proposed, controlled studies
have shown no positive effect for corticosteroids in
enhancing the recovery of the motor deficit.
 Recovery takes up to 24 months because of the
slow rate of axonal regeneration.

26. PATHOGENESIS

27. PATHOGENESIS
 Hyperglycemia generates rheological changes that
increase endoneurial vascular resistance and
reduce nerve blood flow.
 Hyperglycemia also causes depletion of nerve
myoinositol through a competitive uptake
mechanism and activates protein kinase C.
 In addition, persistently elevated blood glucose
levels activate the polyol pathway in nerve tissue
through the enzyme, aldose reductase, which leads
to the accumulation of sorbitol and fructose in nerve
and enhancement of nonenzymatic glycosylation of
structural nerve proteins.

28.  Another adverse effect of hyperglycemia is
autooxidation of glucose, which results in the
generation of toxic reactive oxygen intermediates.
 Overly exuberant activation of protein kinase C has
been linked to vascular damage in diabetic
neuropathy.
 These metabolic changes are likely to cause
abnormal neuronal/axonal and Schwann cell
metabolism and impaired axonal transport.

29. TREATMENT
Despite major advances in diabetes treatment in
general, to date, there is a paucity of U.S. Food and
Drug Administration–approved therapies that
effectively target reversal of the underlying nerve
damage.

30. TREATMENT
 The cornerstone in the treatment of diabetes and its
complications remains optimal glucose control.
 Good diabetic control is associated with less frequent and less
severe peripheral nerve complications
 ACCORD trial- At the end of the study, new cases of neuropathy were
significantly reduced in the intensive treatment group, but no significant
difference was found at the time of transition to standard therapy.
 ADVANCE trial- New or worsening neuropathy, a secondary outcome,
was not found to be significantly affected by intensive glucose
control after a median follow-up of 5 years.
 DCCT- showed that intensive glucose management by insulin pump or by
multiple daily insulin injections in patients with IDDM reduces the
development of neuropathy by 64% at 5 years compared to conventional
therapy. Recent follow-up studies of the DCCT study cohort indicate that
the beneficial effect of intensive glucose management persisted for at
least 8 years after the completion of DCCT, underscoring the importance
of continuous good diabetes control.
 Successful pancreatic transplantation is beneficial in preventing
the progression of diabetic neuropathy, and the effect may be
sustained in long-term follow-up.

31.  Use of high-dose IVIG or methylprednisolone has
been reported to benefit patients with progressive
deficits.
 The long-term use of corticosteroids in diabetic
patients is, however, problematic.

32.  Trials of α-lipoic acid, (oral or IV) showed benefit in
reducing neuropathic symptoms and deficits.
 α-linoleic acid showed lessening of neuropathic
deficits and improvement in measures of nerve
conduction.
 VEGF gene transfer into small mammals has been
shown to improve NCVs, increase blood vessel
density, and enhance nerve blood flow.
 Human C-peptide prevents neuropathy in diabetic
rats in a dose-dependent fashion.

33.  Attempts to treat diabetic neuropathy by
manipulating nerve metabolism have been
disappointing.
 Clinical trials of myoinositol supplementation have
shown conflicting results
 Results of aldose reductase inhibitors have so far failed.
 Neurotrophin treatments for diabetic neuropathy, such
as nerve growth factor, have been disappointing

35.  V. Bril, J. England, G.M. Franklin, et al. Evidence-based guideline: Treatment of painful diabeticneuropathy : Report of the
American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the
American Academy of Physical Medicine and Rehabilitation .Neurology 76 May 17, 2011
OPTIONS FOR PAINFUL DIBETIC NEUROPATHY

36. MOST IMPORTANT OF ALL
“Diabetic Neuropathy is The Presence Of Symptoms
And/Or Signs Of Peripheral Nerve Dysfunction In People
With Diabetes After The Exclusion Of Other Causes”
Boulton AJM, Gries FA, Jervell JA: Guidelines for the diagnosis and outpatient management
of diabetic peripheral neuropathy. Diabetic Med 15:508–514, 1998
“Also 10-55% patients with diabetic neuropathies may have
other conditions that cause similar manifestations- CIDP,
vitamin B12 deficiency, alcoholic neuropathy etc”
Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O'Brien
PC, Melton LJ 3rd, Service FJ. The prevalence by staged severity of various types of
diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the
Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr;43(4):817-24.

37. IN CONCLUSION
 Common diabetic
microvascular
complication.
 Can be caused by
etiologies other than
diabetes mellitus in
diabetics.
 Distal symmetric
polyneuropathy are the
most prevalent forms.
 Once the diabetic
neuropathy is
established, the existing
damage is largely
irreversible.
 Many doctors incorrectly
assume that the term
diabetic neuropathy is
synonymous with distal
symmetrical
polyneuropathy, because
the latter constitutes
perhaps three fourths of
all diabetic neuropathies.
But there are other
variants as well.
 Tight control of sugars is
a cornerstone of therapy.

39. THANK YOU