BY Dr. Richard Nabhan Senior Consultant Physician, Cardiologist & Diabetologist 29 November 2007 Abu Dhabi, UAE Prevention … Non Communicable Epidemics Session A – Symp # 3

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Diabetic Neuropathy

 About 60-70% of people with diabetes have mild to severe forms of nervous system damage, including:  Impaired sensation or pain in the feet or hands  Slowed digestion of food in the stomach  Carpal tunnel syndrome  Other nerve problems  More than 60% of nontraumatic lower-limb amputations in the United States occur among people with diabetes.

Risk Factors Glucose control Duration of diabetes Damage to blood vessels Mechanical injury to nerves Autoimmune factors Genetic susceptibility Lifestyle factors –Smoking –Diet

Pathogenesis of Diabetic Neuropathy Metabolic factors –High blood glucose –Advanced glycation end products –Sorbitol –Abnormal blood fat levels Ischemia

Diagnostic Tests Assess symptoms - muscle weakness, muscle cramps, prickling, numbness or pain, vomiting, diarrhea, poor bladder control and sexual dysfunction Comprehensive foot exam –Skin sensation and skin integrity –Quantitative Sensory Testing (QST) –X-ray Nerve conduction studies Electromyographic examination (EMG) Ultrasound

Classification of Diabetic Neuropathy Symmetric polyneuropathy Autonomic neuropathy Polyradiculopathy Mononeuropathy

Symmetric Polyneuropathy Most common form of diabetic neuropathy Affects distal lower extremities and hands (“stocking- glove” sensory loss) Symptoms/Signs –Pain –Paresthesia/dysesthesia –Loss of vibratory sensation

Complications of Polyneuropathy Ulcers Charcot arthropathy Dislocation and stress fractures Amputation - Risk factors include: –Peripheral neuropathy with loss of protective sensation –Evidence of increased pressure (callus) –Peripheral vascular disease –History of ulcers or amputation –Severe nail pathology

Treatment of Symmetric Polyneuropathy Glucose control Pain control –Tricyclic antidepressants –Topical creams –Anticonvulsants Foot care

Essentials of Foot Care Examination –Annually for all patients –Patients with neuropathy - visual inspection of feet at every visit with a health care professional Advise patients to: –Use lotion to prevent dryness and cracking –Cut toenails weekly or as needed –Always wear socks and well-fitting shoes

Autonomic neuropathy Affects the autonomic nerves controlling internal organs –Peripheral –Genitourinary –Gastrointestinal –Cardiovascular Is classified as clinical or sub-clinical based on the presence or absence of symptoms

Peripheral Autonomic Dysfunction Contributes to the following symptoms/signs: –Neuropathic arthropathy (Charcot foot) –Aching, pulsation, tightness, cramping, dry skin, pruritus, edema, sweating abnormalities –Weakening of the bones in the foot leading to fractures

Peripheral Autonomic Dysfunction, cont. Treatment –Foot care/elevate feet when sitting –Eliminate aggravating drugs –Reduce edema –diuretics –Support stockings –Screen for CVD

Genitourinary Autonomic Neuropathy

Gastrointestinal Autonomic Neuropathy Symptoms/Signs –Gastroparesis resulting in anorexia, nausea, vomiting, and early satiety –Diabetic enteropathy resulting in diarrhea and constipation Treatment –Other causes of gastroparesis or enteropathy should first be ruled out –Gastroparesis - Small, frequent meals, metoclopramide, erythromycin –Enteropathy - loperamide, antibiotics, stool softeners or dietary fiber

Cardiovascular Autonomic Neuropathy Symptoms/Signs –Exercise intolerance –Postural hypotension Treatment –Discontinue aggravating drugs –Change posture (make postural changes slowly, elevate bed) –Increase plasma volume

Polyradiculopathy Lumbar polyradiculopathy (diabetic amyotrophy) –Thigh pain followed by muscle weakness and atrophy Thoracic polyradiculopathy –Severe pain on one or both sides of the abdomen, possibly in a band-like pattern Diabetic neuropathic cachexia –Polyradiculopathy + peripheral neuropathy –Associated with weight loss and depression

Polyradiculopathy, cont. Polyradiculopathies are diagnosed by electromyographic (EMG) studies Treatment –Foot care –Glucose control –Pain control

Mononeuropathy Peripheral mononeuropathy –Single nerve damage due to compression or ischemia –Occurs in wrist (carpal tunnel syndrome), elbow, or foot (unilateral foot drop) –Symptoms/Signs numbness edema pain prickling

Cranial mononeuropathy –Affects the 12 pairs of nerves that are connected with the brain and control sight, eye movement, hearing, and taste –Symptoms/Signs unilateral pain near the affected eye paralysis of the eye muscle double vision Mononeuropathy multiplex Mononeuropathy, cont.

Treatment –Foot care –Glucose control –Pain control

Other Treatment Options ACE inhibitors Weight control Exercise

Diabetic Nephropathy

 Over 40% of new cases of end- stage renal disease (ESRD) are attributed to diabetes.  In 2001, 41,312 people with diabetes began treatment for end- stage renal disease.  In 2001, it cost $22.8 billion in public and private funds to treat patients with kidney failure.  Minorities experience higher than average rates of nephropathy and kidney disease

Five Stages of Kidney Disease Stage 1: Hyperfiltration, or an increase in glomerular filtration rate (GFR) occurs. Kidneys increase in size. Stage 2: Glomeruli begin to show damage and microalbuminurea occurs. Stage 3: Albumin excretion rate (AER) exceeds 200 micrograms/minute, and blood levels of creatinine and urea-nitrogen rise. Blood pressure may rise during this stage.

Five Stages of Kidney Disease (con’t.) Stage 4: GFR decreases to less than 75 ml/min, large amounts of protein pass into the urine, and high blood pressure almost always occurs. Levels of creatinine and urea-nitrogen in the blood rise further. Stage 5: Kidney failure, or end stage renal disease (ESRD). GFR is less than 10 ml/min. The average length of time to progress from Stage 1 to Stage 4 kidney disease is 17 years for a person with type 1 diabetes. The average length of time to progress to Stage 5, kidney failure, is 23 years.

Screening for Diabetic Nephropathy 1 American Diabetes Association: Nephropathy in Diabetes (Position Statement). Diabetes Care 27 (Suppl.1): S79-S83, 2004

Treatment of Diabetic Nephropathy Hypertension Control - Goal: lower blood pressure to <130/80 mmHg –Antihypertensive agents Angiotensin-converting enzyme (ACE) inhibitors –captopril, enalapril, lisinopril, benazepril, fosinopril, ramipril, quinapril, perindopril, trandolapril, moexipril Angiotensin receptor blocker (ARB) therapy –candesartan cilexetil, irbesartan, losartan potassium, telmisartan, valsartan, esprosartan Beta-blockers

Glycemic Control –Preprandial plasma glucose mg/dl –A1C <7.0% –Peak postprandial plasma glucose <180 mg/dl –Self-monitoring of blood glucose (SMBG) –Medical Nutrition Therapy Restrict dietary protein to RDA of 0.8 g/kg body weight per day Treatment of Diabetic Nephropathy (cont.)

Treatment of End-Stage Renal Disease (ESRD) There are three primary treatment options for individuals who experience ESRD: 1. Hemodialysis 2. Peritoneal Dialysis 3. Kidney Transplantation

How Can You Prevent Diabetic Kidney Disease? Maintain blood pressure <130/80 mm/Hg Maintain preprandial plasma glucose mg/dl Maintain postprandial plasma glucose <180 mg/dl Maintain A1C <7.0%

Diabetic Retinopathy

Diabetic retinopathy is the most common cause of new cases of blindness among adults years of age. Each year, between 12,000 to 24,000 people lose their sight because of diabetes. During the first two decades of disease, nearly all patients with type 1 diabetes and over 60% of patients with type 2 diabetes have retinopathy

Risks of Diabetic Retinopathy Related Vision Loss Duration of diabetes disease –It was demonstrated that type 1 patients experience a 25% rate of retinopathy after 5 years of disease, and 80% at 15 years of disease 1 –Up to 21% of newly diagnosed type 2 patients have some degree of retinopathy at time of diagnosis 1 Puberty Pregnancy Lack of appropriate ophthalmic examination

Retinopathy Screening Type 1 diabetes - screen within 3-5 years of diagnosis after age 10 Type 2 diabetes - screen at time of diagnosis 1 Pregnancy - women with preexisting diabetes should be screened prior to conception and during first trimester Follow-up annually; less frequent exams (2-3 yrs) may be considered Examination Methods - Dilated indirect ophthalmoscopy coupled with biomicroscopy and seven-standard field steroscopic 30° fundus photography

Natural History of Diabetic Retinopathy Mild nonproliferative diabetic retinopathy (NPDR) Moderate NPDR Severe NPDR Very Severe NPDR Proliferative diabetic retinopathy (PDR)

Mild NPDR Clinical Findings –Increased vascular permeability –Microaneurysms –Intraretinal hemorrhages –Clinically Significant Macular Edema (CSME) possible Management/Treatment –Annual follow-up –If CSME present: color fundus photography, fluorescein angiography, and photocoagulation

Moderate NPDR Clinical Findings –Venous caliber changes –Intraretinal Microvascular Abnormalities (IRMAs) –CSME possible Management/Treatment –6-12 month follow-up without CSME –Color fundus photography –CSME present: color fundus photography, fluorescein angiography, focal photocoagulation, 3-4 month follow-up

Severe/Very Severe NPDR Clinical Findings –Retinal ischemia –Extensive hemorrhage and microaneurysms –CSME possible Management/Treatment –3-4 month follow-up –Color fundus photography –Possible panretinal photocoagulation –CSME present: color fundus photography, fluorescein angiography, focal photocoagulation, 3-4 month follow-up

PDR Clinical Findings –Ischemia induced neovascularization at the optic disk (NVD) elsewhere in the retina (NVE) –Vitreous hemorrhage –Retinal traction, tears, and detachment –CSME possible

PDR, cont. Management/Treatment –2-4 month follow-up –Color fundus photography –Panretinal photocoagulation (3-4 month follow-up) –Vitrectomy –CSME present: focal photocoagulation, fluorescein angiography

Prevention of Diabetic Retinopathy Associated Vision Loss Intensive glycemic control Tight blood pressure control (<130/80 mmHg) Comprehensive eye examinations