History

Fact Explanation
Paraesthesiae in feet [1][2] Occurs due to diabetic polyneuropathy. Sensory neuropathy that affects small nerve fibers cause painful anesthesia.[1][2]
Dull, aching and/ or lancinating, pain in lower limbs, worse at night[1][2] Occurs due to diabetic polyneuropathy. Sensory neuropathy that affects small nerve fibers cause painful anesthesia.[1][2] Neuropathic pain has a diurnal variation. [3]
Loss of sweating[1][2] Occurs due to diabetic autonomic neuropathy. Sweat gland is a complex structure with a cholinergic innervation. In diabetics there is a wide spread lesion in small nerve fibers[7].
Orthostatic hypotention[1][2] Occurs due to diabetic autonomic neuropathy. Blood pressure regulation in erect posture maintains by both neural and humoral factors.[4] In diabetes this occurs usually due to the damage of the efferent sympathetic vasomotor fibers, especially in the splanchnic vasculature.[5]
Gastroparesis and diarrhoea[1][2] Occurs due to diabetic autonomic neuropathy. Gastroparesis - Gastric emptying needs proper action of smooth muscle, enteric and extrinsic autonomic nerves, and specialized pacemaker cells, the interstitial cells of Cajal. Diabetes may result in gastric motor dysfunction which include autonomic neuropathy, enteric neuropathy involving excitatory and inhibitory nerves, abnormalities of interstitial cells of Cajal, acute fluctuations in blood glucose, incretin-based medications used to normalize postprandial blood glucose and psychosomatic factors. [6] Diarrhoea - Due to autonomic dysfunction there is impaired motility in the small bowels.Bacterial overgrowth due to stasis of the bowel may contribute to diarrhea [5]
Erectile dysfunction[1][2] In diabetes this occurs due to multifactorial etiologies, Neuropathy, metabolic control, vascular disease, nutrition, endocrine disorders, psychogenic factors and anti-diabetic drugs [5]
Gustatory sweating[1][2] Occurs due to diabetic autonomic neuropathy. Even though aberrant nerve regeneration has been suggested as a possible mechanism, exact mechanism is still unknown. [7]
Neuropathic ulcers[1][2] Occurs due to multiple factors associate with diabetics, which include neuropathy, vascular disease and immunopathy [8]. Mainly due to the sensory neuropathy in which protective sensation is lost. [7]
Difficulty in micturition, urinary incontinence, reccurent infection due to atonic bladder[1][2] Occurs due to diabetic autonomic neuropathy. It affects the sacral nerves and impairs detrusor muscle while pudendal innervation of perineal and periurethral striated muscle is usually unaffected in diabetic neuropathy[7].
References
  1. Lindsay, K. W., Bone, I., Fuller, G., & Callander, R. (2011). Neurology and neurosurgery illustrated. Edinburgh: Churchill Livingstone/Elsevier.p441-2
  2. Boon, N. A., Colledge, N.R., Walker,B.R., Hunter, J.(2006). Davidson's Principles and Practice of Medicine.Edinburgh: Churchill Livingstone/Elsevier.p843-4
  3. GILRON I, BAILEY JM, VANDENKERKHOF EG. Chronobiological characteristics of neuropathic pain: clinical predictors of diurnal pain rhythmicity. Clin J Pain [online] 2013 Sep, 29(9):755-9 [viewed 15 May 2014] Available from: doi:10.1097/AJP.0b013e318275f287
  4. Christlieb, A. R., Munichoodappa, C., & Braaten, J. T. (1974). Decreased response of plasma renin activity to orthostasis in diabetic patients with orthostatie hypotension. Diabetes, 23(10), 835-840.
  5. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821
  6. CAMILLERI M, BHARUCHA AE, FARRUGIA G. Epidemiology, Mechanisms and Management of Diabetic Gastroparesis Clin Gastroenterol Hepatol [online] 2011 Jan, 9(1):5-e7 [viewed 15 May 2014] Available from: doi:10.1016/j.cgh.2010.09.022
  7. WATKINS P, THOMAS P. Diabetes mellitus and the nervous system J Neurol Neurosurg Psychiatry [online] 1998 Nov, 65(5):620-632 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170362
  8. Wieman, T. J., Smiell, J. M., & Su, Y. (1998). Efficacy and Safely of a Topical Gel Formulation of Recombinant Human Platelet-Derived Growth Factor-BB (Becaplermin) in Patients With Chronic Neuropathic Diabetic Ulcers: A phase III randomized placebo-controlled double-blind study. Diabetes care, 21(5), 822-827.

Examination

Fact Explanation
'glove and stoking' type sensory loss[1] Occurs due to diabetic sensory polyneuropathy. small myelinated and unmyelinated axons become impaired.[1] Longest nerve fibers are affected first[6].
Dry skin[1] Occurs due to diabetic autonomic neuropathy. Sweat gland is a complex structure with a cholinergic innervation. In diabetics there is a lesion in small nerve fibers that supply to the skin and the sweating get impaired.[1]
Orthostatic hypotention[1] Occurs due to diabetic autonomic neuropathy. In any condition orthostatic hypotention can be occur due to defective contraction of resistance vessels in the standing position or abnormal reduction in blood volume or diminished cardiac output in the standing position due either to reduced venous return or to inability to accelerate the heart, or both. In long term diabetes above mention all three factors may be involved.[2] In diabetes this occurs usually due to the damage of the efferent sympathetic vasomotor fibers, especially in the splanchnic vasculature.[3]
Fixed heart rate and Resting tachycardia[1] Occurs due to diabetic autonomic neuropathy. There is combined vagal and sympathetic impairment, the rate remains elevated.[3]
Loss of vibratory sensation and joint position sensation[1] Large myelinated fibers and other proprioceptive afferent fibers impairment leads to disturbance of light touch sensation, sensibility to pressure and vibration, and joint position sense.[5]
Cranial nerve palsies Third, sixth and seventh nerve palsy occurs due to diabetic associated central nervous system involvement.[6]
Neuropathic osteoarthropathy (Charcot joints)[1] Occurs due to diabetic associated multifactorial etiological factors. Neuropathic joint degeneration, recurrent trauma due to loss of protective joint sensation and osteopenia, possibly because of increased blood flow from sympathetic denervation, are the main predisposing factors. [1]
Loss of muscle power and muscle wasting[1] Occurs due to proximal diabetic neuropathy of the lower limbs, wasting of the quadriceps and loss of the patellar reflex occur at an early stage in the disease[5]. In nerve biopsies immune-mediated epineurial microvasculitis has been reported[7].
References
  1. WATKINS P, THOMAS P. Diabetes mellitus and the nervous system J Neurol Neurosurg Psychiatry [online] 1998 Nov, 65(5):620-632 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170362
  2. HILSTED J, PARVING HH, CHRISTENSEN NJ, BENN J, GALBO H. Hemodynamics in diabetic orthostatic hypotension. J Clin Invest [online] 1981 Dec, 68(6):1427-1434 [viewed 16 May 2014] Available from: doi:10.1172/JCI110394
  3. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821
  4. Vinik, A. I., & Ziegler, D. (2007). Diabetic cardiovascular autonomic neuropathy. Circulation, 115(3), 387-397.
  5. SAID G. Diabetic neuropathy--a review. Nat Clin Pract Neurol [online] 2007 Jun, 3(6):331-40 [viewed 15 May 2014] Available from: doi:10.1038/ncpneuro0504
  6. WATANABE K, HAGURA R, AKANUMA Y, TAKASU T, KAJINUMA H, KUZUYA N, IRIE M. Characteristics of cranial nerve palsies in diabetic patients. Diabetes Res Clin Pract [online] 1990 Aug-Sep, 10(1):19-27 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2249603
  7. BOULTON AJ, VINIK AI, AREZZO JC, BRIL V, FELDMAN EL, FREEMAN R, MALIK RA, MASER RE, SOSENKO JM, ZIEGLER D, AMERICAN DIABETES ASSOCIATION. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care [online] 2005 Apr, 28(4):956-62 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15793206

Differential Diagnoses

Fact Explanation
Amyloidosis [1] In a patient with a small-fiber sensory polyneuropathy with autonomic features [1]
Lepromatous leprosy[1] In a patient from an endemic area and without autonomic symptoms[1]
Vitamin B12 deficiency[1] In a patients with pure sensory neuropathy with large fiber involvement[1]
Chronic inflammatory demyelinating polyneuropathy[1] In a patients with prominent motor involvement.[1]
References
  1. Thomas, P. (1997). Classification, differential diagnosis, and staging of diabetic peripheral neuropathy. Diabetes, 46(Supplement 2), S54-S57.

Investigations - for Diagnosis

Fact Explanation
Nerve conduction test[1] Velocity of the nerve conduction is slow due to the demyelination and loss of large myelinated fibers, and a decrease in nerve action potentials owing to loss of axons[1].
Cardiovascular reflex tests[2] It is used to diagnose cardiovascular autonomic dysfunction. It consist of five non invasive cardiovascular reflex tests, Valsalva maneuver,heart rate response to deep breathing, heart rate response to standing up, blood pressure response to standing up, and blood pressure response to sustained hand grip. [2]
Upper GI endoscopy or barium studies[2] To rule out structural or mucosal abnormalities of the GI tract in diabetic gastropheresis.[2]
References
  1. SAID G. Diabetic neuropathy--a review. Nat Clin Pract Neurol [online] 2007 Jun, 3(6):331-40 [viewed 15 May 2014] Available from: doi:10.1038/ncpneuro0504
  2. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821

Investigations - Fitness for Management

Fact Explanation
Electrocardiography (ECG\EKG) [1] To asses cardiac function, and detect ischemic changes [1]
Plasma glucose levels [1] To asses glycemic contol [1]
References
  1. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821

Investigations - Followup

Fact Explanation
Electrocardiography (ECG\EKG) [1] To asses cardiac function, and detect ischemic changes [1]
Plasma glucose levels [1] To asses glycemic contol [1]
Renal function tests, urine culture, postvoid ultrasound and cystrometry [1] To asses bladder function [1]
References
  1. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821

Investigations - Screening/Staging

Fact Explanation
Assessment of sensory function [1] All patients should screen for sensory impairment annually. It starts with the diagnosis of type 2 Diabetes melitus or 5 years after the diagnosis of type 1 diabetes. Pinprick method, temperature, vibration perception(using a 128Hz tuning fork) and pressure sensation (using 10g monofilament) is done to assess this[1].
References
  1. BOULTON AJ, VINIK AI, AREZZO JC, BRIL V, FELDMAN EL, FREEMAN R, MALIK RA, MASER RE, SOSENKO JM, ZIEGLER D, AMERICAN DIABETES ASSOCIATION. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care [online] 2005 Apr, 28(4):956-62 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15793206

Management - General Measures

Fact Explanation
Maintain optimum glycemic control[1] To prevent developing diabetic neuropathy[1]
Foot care[1] To prevent foot ulcers and bone infections[1]
Improve nutrition, reduce fat, alcohol and tobacco consumption [2] to prevent end organ damage [2]
References
  1. SAID G. Diabetic neuropathy--a review. Nat Clin Pract Neurol [online] 2007 Jun, 3(6):331-40 [viewed 15 May 2014] Available from: doi:10.1038/ncpneuro0504
  2. VINIK AI, MASER RE, MITCHELL BD, FREEMAN R. Diabetic autonomic neuropathy. Diabetes Care [online] 2003 May, 26(5):1553-79 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12716821

Management - Specific Treatments

Fact Explanation
Intensive insulin therapy [1] To achieve strict diabetic control[1]
Pain management[1] Carbamazepine, phenytoin, clonazepam, or paracetamol in combination with codeine phosphate can be useful. Tricyclic antidepressants, such as imipramine or amitriptyline, are often effective; the usual dose varies from 30–150 mg per day. Tricyclic antidepressants might aggravate postural hypotension. The recently introduced drugs duloxetine and pregabalin are also useful.[1]
Management of symtomatic postural hypotention.[1] Midodrine - alpha adrenoceptor antagonist (not license in everywhere) is more effective than using 9-alpha-fluorohydrocortisone, which is the most effective treatment for postural hypotension but carries a risk of hypertension. [1]
Management of Gastroinestinal neuropathy [2] 1- Gastroparesis - Frequent small meals, prokinetic agents (metoclpramide, domperidone) 2- Abdominal pain or discomfort, early satiety, nausea, vomiting, belching, bloating - Antibiotics, antiemetics (phenergan, compazine, tigan, scopolamine), bulking agents, tricyclic antidepressants, pancreatic extracts, pyloric Botox, gastric pacing, enteral feeding 3- Diarrhea, often nocturnal alternating with constipation and incontinence - Trials of soluble fiber, gluten and lactose restriction, anticholinergic agents, cholestyramine, antibiotics, clonidine, somatostatin, pancreatic enzyme supplements [2]
Management of Erectile dysfunction[2] Sex therapy, psychological counseling, sildenafil, vardenafil, tadalafil, prostaglandin E1 injection, device or prosthesis[2]
Management of Bladder dysfunction[2] Bethanechol, intermittent catheterization[2]
Management of sweating dysfunction[2] Emollients and skin lubricants, scopolamine, glycopyrrolate, botulinum toxin, vasodilators[2]
References
  1. SAID G. Diabetic neuropathy--a review. Nat Clin Pract Neurol [online] 2007 Jun, 3(6):331-40 [viewed 15 May 2014] Available from: doi:10.1038/ncpneuro0504
  2. BOULTON AJ, VINIK AI, AREZZO JC, BRIL V, FELDMAN EL, FREEMAN R, MALIK RA, MASER RE, SOSENKO JM, ZIEGLER D, AMERICAN DIABETES ASSOCIATION. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care [online] 2005 Apr, 28(4):956-62 [viewed 15 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15793206