Ambulatory:Diabetes Mellitus

April 9, 2007

Insulin dependent (Type 1 /IDDM) Abrupt onset, < 30 yrs Autoimmune insulin deficiency due to islet cell

destruction Prone to ketoacidosis

Non-insulin dependent (Type 2/NIDDM) Gradual onset, > 30 yrs Obesity Insulin resistance Impaired insulin secretion (beta cell dysfunction)

Subtypes

Type I DM

Insulin deficiency secondary to β-cell destruction usually by autoimmune process

Insulin and C-peptide levels low May have islet cell autoantibodies,

Autoantibodies to insulin, or antibodies to glutamic acid decarboxylase or tyrosine phosphatases.

20% risk of other autoimmune diseases Typically will present with DKA due to

absolute lack of insulin

Type II

Insulin resistance and relative insulin deficiency - β-cell mass preserved, but decreased secretion and response to insulin.

Strong genetic component with 100% concordance in monozygotic twins.

Ketoacidosis is rare – though it can occur if concurrent infection. Also there are a small group of mainly African American patients in whom insulinopenia leads to a tendency to DKA.

Usually hyperglycemia in Type II develops gradually and pt may be undiagnosed for years.

Subtypes

Gestational Diabetes Dysfunction of glucose metabolism with

presentation in pregnancy Increased fetal morbidity Up to 63% will develop non-gestational DM in 5-

16 years MODY (maturity-onset diabetes of the young)

Subset of Type 2 DM Family history, early age of onset (teens, 20’s) At least 5 subtypes Impairment of β-cell function Resistance to ketoacidosis

Subtypes Secondary Diabetes

Pancreatic disease with resultant insulinopenia

• Chronic pancreatitis, pancreatectomy, CF, hemachromatosis

Drug induced• HCTZ, steroids, estrogen, psychoactive

agents, catacholamines, pentamidine

Subtypes

EndocrinopathiesAcromegaly, pheochromocytoma,

Cushing’s, Conn’s, glucagonomaInsulin receptor abnormalities

Genetic syndromesHyperlipidemia, muscular dystrophies,

Huntington’s chorea

Diagnosis Per the Expert Committee on the Diagnosis and

Classification of Diabetes Mellitus, 2003

Criteria Comment Symptoms of DM Casual plasma glucose concentration ≥ 200 mg/dL OR

Casual defined as any time of day, meal or no meal

** 2 Fasting plasma glucose concentrations ≥ 126 mg/dL OR

No caloric intake for at least 8 hours

2 hour plasma glucose concentration ≥ 200 mg/dL on OGTT

Glucose load equivalent to 75 g of anhydrous glucose in water

Symptoms of Diabetes

ClassicPolyuria, polydipsia, unexplained

weight LOSS Fatigue Blurry vision Nausea, vomiting Infections

Screening for Diabetes

Every 3 years if age 45 or older (if results are normal) More frequent screening if:

Pre-Diabetic• Fasting plasma glucose concentration > 110 mg/dL or < 126 mg dL• a.k.a. “impaired fasting glucose” or “impaired glucose tolerance”

Obese (BMI≥27) 1st degree relatives with DM High risk ethnic group

• African-American, Hispanic-American, Native-American, Asian-American, Pacific Islander-American

Pregnancy • History of Gestational diabetes• Delivery of baby weighing 9 or more pounds

HTN (>140/90) Dyslipidemia

• HDL≤35 mg/dL, TGL≥250 mg/dL

Treatment rationale

DCCTRG39% reduction in progression of

retinopathy for 0.9% reduction in HbA1c

UKPDSGHbA1c of 7% associated with

significant incidence of micro and macrovascular disease

Treatment Rationale

Meticulous glucose control decreases long-term microvascular complication rates

Aggressive insulin therapy in patients with a recent MI was associated with reduced mortality

Treatment of Diabetes Mellitus

Goals set by American Diabetes AssociationPreprandial glucose values of 80 to 120

mg/dLBedtime glucose values of 100 to 140

mg/dLHemoglobin A1C < 7%2 hour post-prandial glucose values <

160 mg/dL

Need insulin Healthy people generally have insulin

production of 24-36 units per day Type 1 DM

0.5 to 1.0 units/kg of insulin daily Varies according to diet, exercise, stress

Various insulin preparations with various regimens Tailor to the patient Attempt to mimic the healthy person’s insulin

peaks and valleys

Treatment of Type 1 Diabetes Mellitus

Rapid Acting Insulins Lispro, Aspart

Short Acting Insulins Regular

Intermediate Acting NPH Lente

Long Acting Ultralente Glargine

Treatment of Type 1 Diabetes Mellitus

Pharmacokinetics of current insulin preparations

Insulin Onset Peak Effective duration

Lispro (Humalog) <15 min 1 hr 4-5 hr

Regular 0.5-1 hr 2-3 hr 5-8 hr

NPH, lente 2-4 hr 6-8 hr 6-16 hr

Ultralente 4 hr Variable 18-22 hr

Glargine (Lantus) 1-2 hr Flat, predictable 22-24 hr

NPH, isophane insulin suspension. Compiled from Barnett and Owens (1), Lepore et al (2), and White et al (3).

Basal/Bolus regimen

Basal/Bolus regimen Daily insulin dose consists of a basal insulin to inhibit

hepatic glucose production and pre-meal insulin to cover intake

• mimics natural insulin production Typically this is achieved with Lantus QHS and Novolog

(aspart) QAC. Patients on this regimen should either be given a Sliding

scale instructing them how to cover their premeal accuchecks and how to “Carb count” OR they need a standard dose of premeal insulin which you review when you see them in clinic based on their readings.

15g carbs = 1 unit of insulin Requires multiple insulin injections and accuchecks, but

provides greater flexibility in matching insulin to meal.

Treatment of Type 1 Diabetes Mellitus Pancreas Transplant with or without Kidney

transplant To help protect the transplanted kidney from

hyperglycemia Meet certain criteria, in general, frequent,

acute metabolic complications and failure with insulin therapy

Survival, immunosuppression Pancreatic islet cell transplant

Similar criteria Immunosuppression

Treatment of Type 2 Diabetes

Weight Loss, Diet, Exercise Decrease in body weight as little as 4-7% can help

increase insulin sensitivity United Kingdom Prospective Diabetes Study

(UKPDS)• < 25% treated with diet and exercise alone maintain

Hgb A1C < 7% after 3 years and < 10% after 9 years• Attributed in part to progressive loss of β-cell

secretion of insulin Supporting evidence of dual therapy with oral

agents, i.e. one agent augmenting insulin secretion, another improving insulin action

Treatment of Type 2 Diabetes

Insulin Secretagogues (“Beta-beaters”) Sulfonylurea Meglitinides

Biguanides – decrease hepatic gluconeogenesis Metformin

Thiazolidinediones – insulin sensitizer The “glitizones”

Alpha-glucosidase Inhibitors – decreased GI absorption Acarbose

Sulfonylurea First line after diet and exercise 20-25% primary failure rate Caution in hepatic/renal dysfunction Mechanism of action

Promote increased pancreatic secretion Side effects

Hypoglycemia, usually within 1st 4 months• Increased in elderly, worsening renal function, irregular meal schedules

Weight gain Medications

Glyburide (Micronase, Diabeta)• Duration of action 18-24 hours• Hypoglycemia still common

Glipizide (Glucotrol) Glimepiride (Amaryl)

• Indicated for use with insulin• “safe” in renal failure

Meglitinides (rapid acting secretogogues)

Theoretically offers improved post prandial control May benefit patients with unpredictable meal schedules or

large post prandial glucose levels Q meal dosing

Mechanism of action Similar to sulfonylureas, quicker “on-off” action

Side effects Hypoglycemia Weight gain

Medications Repaglinide (Prandin) Nataglinide (Starlix)

• Ultra short acting• Most effective agent for post-prandial control• Hypoglycemic contraindication with insulin

Biguanides Weight loss due to appetite reduction Less hypoglycemia than sulfonylurea therapy Major effects:

Increased hepatic insulin sensitivity Decreased gluconeogenesis and glycogenolysis

Side effects LACTIC ACIDOSIS GI intolerance

Mechanism of action is unclear Medication

Metformin (Glucophage)• Optimal dose 2000mg/d• BID dosing

Biguanides

Contraindications to metformin Serum creatinine >= 1.5 mg/dL in men, >=

1.4 mg/dL in women Age > 75years Discontinue before any radiologic contrast

studies (stop during or before) or upon hospitalization

Hepatic dysfunction Dehydration Metabolic acidosis CHF requiring treatment

Thiazolidinediones (TZD) Mechanism of action

Not fully understood Decrease insulin resistance, increase insulin sensitivity, probably at the

peripheral skeletal muscle ? Smaller effect on liver gluconeogenesis

Additive effect with metformin Favorable lipid profile effects, ? atherosclerosis Side effects

Weight gain Edema – caution with CHF Hypoglycemia, especially if coupled with other diabetic medication Liver dysfunction? – monitor LFTs

Medications Rosiglitizone (Avandia) - increase HDL levels Pioglitizone (Actos) - increase HDL, decrease TG levels

Contraindicated: Hepatic dysfunction Age greater than 80 Advanced CHF

Thiazolidinediones (TZD)

Monotherapy or combo with metformin, sulfonylureas, and insulin

Other effects:• Slightly reduce BP• Enhance fibrinolysis• Improve endothelial function

Alpha-glucosidase Inhibitors

Decreases digestion of complex carbohydrates in small bowel

Slows monosaccharide absorption Effective only with diets >40% carbohydrates Lowers post-prandial>pre-prandial glucose Not as efficacious as other agents (decreases A1C by

0.5% - 1%) Side effects major limitation

Gas, abdominal pain, diarrhea Minimized with slow titration

Medications Acarbose (Precose) Miglitol (Glyset)

Oral Agent Monotherapy and Glycemic Control

Drug Baseline HbA1c

Decrease in HbA1c (%)

Sulfonylurea

Glipizide XL 8.7 1.8

Glimepiride 8.1 1.9

Rapid acting secretogogue

Repaglinide 8.7 1.8

Nateglinide 8.1 0.9

Biguanide

Metformin 8.4 1.8

Alpha-glucosidase Inhibitor

Miglitol 8.9 0.74

Thiazolidinediones

Rosiglitazone 8.8 1.5

Pioglitazone 10.3 1.6

Miscellaeous

Glucovance 8.2 1.5

Combination Oral Therapy

Lowers A1C levels by about 2% No evidence that a specific

combination is any more effective in lowering glucose levels or more effective in preventing complications than another

Thus, patients with an HbA1C >9% who are receiving monotherapy are unlikely to reach a target of <7%

A 56-year-old woman who has had type 2 diabetes mellitus for 12 years is evaluated because of poorly controlled diabetes. She is obese (body mass index, 32 kg/m2). She takes glyburide, and over the past 6 months, her hemoglobin A1C level has increased from 6.8% to 8.5%, while measurements of her fasting plasma glucose have been greater than 200 mg/dL and postprandial measurements range from 250 to 350 mg/dL. She refuses to take insulin.

Which of following is the best therapy for this patient? ( A ) Discontinue glyburide and initiate metformin

( B ) Discontinue glyburide and initiate a thiazolidinedione( C ) Continue glyburide and add metformin( D ) Continue glyburide and repeat measurement of hemoglobin A1C( E ) Continue glyburide and add acarbose

Critique (Correct Answer = C)

Type 2 diabetes mellitus is a progressive disorder, and studies have documented that response to monotherapy is limited. Four options are available to obese patients who have become unresponsive to sulfonylureas: 1) add metformin, 2) add a thiazolidinedione, 3) add an α-glucosidase inhibitor, and 4) add insulin. Arguably the best treatment could be to initiate insulin at bedtime and continue the sulfonylurea.

There is no consensus about which option is most effective. Adding metformin to the regimen provides an effective agent that complements the action of sulfonylurea. Several studies document that fasting plasma glucose and hemoglobin A1C values decline with this combination of sulfonylurea and metformin in patients with body mass indexes in the range of 27 to 30 kg/m2. Maximum dosages (2000 mg) of metformin should be administered in divided doses. A trial of this combination for 6 to 8 weeks should determine its effectiveness. If hemoglobin A1C values do not fall to the 7.0% to 7.5% range, the patient should be encouraged to start insulin therapy.

A thiazolidinedione and acarbose (an α-glucosidase inhibitor) are less powerful as hypoglycemic agents than sulfonylureas and metformin, and probably would be less effective in this patient than combination therapy. The patient’s obesity indicates that insulin resistance is a likely factor in the progressive hyperglycemia, and a thiazolidinedione warrants consideration; however, if it is used, greater laboratory monitoring is required.

Oral Agent Metabolic Effects Sulfonylurea Rapid acting

secretogogues Metformin Thiazoidiniones

Insulin Resistance

0 0 Marked decrease

Marked decrease

Hyperinsulinemia 0 0 Marked decrease

Marked decrease

LDL 0 0 Small decrease

Small decrease

HDL 0 0 0 Marked increase

Triglycerides 0 0 Small decrease

Moderate decrease

LP(a) 0 0 Moderate decrease

Moderate decrease

Body weight Moderate increase

Moderate increase

Moderate decrease

Moderate increase

A 52-year-old woman is found to have a fasting plasma glucose concentration of 168 mg/dL during her annual physical examination. Her lifestyle is sedentary. Obesity has been a problem since early adulthood, and her weight in recent years has ranged from 90 to 103 kg (196 to 226 lb). Her blood pressure has been elevated for the past 18 years, and while taking captopril, it is in the 160/90 to 180/100 range. The hemoglobin A1C level is 8.4%.

After meeting with a dietitian and nurse educator, she starts a calorie-restricted diet and an exercise program; 6 weeks later, she weighs 91.8 kg (202 lb) and her hemoglobin A1C is 8.6%. Other laboratory tests include a total cholesterol of 238 mgldL and a fasting triglyceride level of 278 mgldL.

What is the best hypoglycemic agent for this patient? ( A ) Insulin

( B ) A sulfonylurea( C ) Metformin( D ) Acarbose( E ) Rosiglitazone

Critique (Correct Answer = C)

Persistent hyperglycemia and hypertriglyceridemia in an obese patient make metformin an ideal agent. The drug will facilitate weight loss and have beneficial effects on the hypertriglyceridemia. The United Kingdom Prospective Diabetes Study indicated that insulin and sulfonylureas equally lower plasma glucose but do not help weight loss or prevent weight gain. The thiazinolinediones as monotherapy also increase weight as well as possibly adversely affecting serum cholesterol levels. Although metformin as well as insulin and sulfonylureas reduce hyperglycemia and consequently lower the risk for the several microvascular complications, these agents do not significantly alter the risk for myocardial infarction.

Insulin is most effective as the first choice in symptomatic patients, especially those who are normal weight or only slightly overweight. In the setting of infection, a vascular accident, or other medical problem, the patient with recent-onset type 2 disease benefits from insulin as first treatment.

Sulfonylureas would also probably lower plasma glucose in this patient, but weight gain or inability to lower weight are possible complications. In 10% to 15% of recently diagnosed patients, sulfonylureas are ineffective as hypoglycemic agents. The exact cause of this primary failure is unclear, although beta cells exposed to hyperglycemia for prolonged periods will not respond to sulfonylureas.

Acarbose is reserved for patients with type 2 diabetes mellitus in whom postprandial hyperglycemia is the major problem. In patients with elevated fasting glucose levels, acarbose will have limited effect.

The thiazolidinediones effectively reduce fasting plasma glucose concentration. These agents increase serum LDL-and HDL cholesterol slightly and lower triglycerides by about 10-15%.

Which one of the following describes the effect of the thiazolidinediones?

( A ) Inducing weight loss effect( B ) Decreasing low-density lipoprotein cholesterol( C ) Increasing production of insulin from pancreatic beta cells( D ) Increasing glucose transporter expression

Critique (Correct Answer = D)

Resistance to the action of insulin is a prime cause of the hyperglycemia in most patients with type 2 diabetes. The thiazolidinediones are a group of drugs that improve sensitivity to insulin in several tissues by binding to PPAR-γ receptors, leading to increased expression of glucose transporters. The agent causes weight gain when used as monotherapy and in combination with insulin. Serum triglyceride values fall, whereas both LDL and HDL cholesterol values increase; the rise in LDL cholesterol in several studies is about 10% to 15%. The currently available thiazolidinediones, rosiglitazone and proglitazone, are equally effective in lowering glucose in patients with type 2 diabetes mellitus. Hemoglobin A1C levels fall about 1.5% in studies of these agents. Several cases of severe liver toxicity have been reported after troglitazone therapy, so it was removed from the market in March of 2000. The U.S. Food and Drug Administration recommends baseline and every 2 month monitoring of liver function tests during the first year of therapy if this class of drugs is used. The incidence of elevated liver enzyme levels in patients treated with proglitazone and rosiglitazone are 0.25% and 0.2% respectively, values similar to those in patients receiving placebos.

Insulin Therapy in Type II DM

Newly diagnosed patients with DM2 have < 50% of normal insulin secretion at diagnosis

< 25% of normal insulin secretion 6 years after diagnosis

Indications for Insulin Therapy in Type II DM

Why More than 30% of type 2 diabetics require insulin Progressive β-cell deterioration Addition of a qHS basal insulin can reduce the Hgb A1C level from 8.6% to 6.9

% (Yale, Annal Int Med, 2001) When

Persistent Fasting plasma glucose ≥ 250 mg/dL Hgb A1C > 8% on maximum oral therapy Hepatic or renal dysfunction that prohibits oral agents All pregnant type II diabetics

• All oral agents are contraindicated How

UKPDS showed combination therapy with insulin and oral agent had better control

No recommended combinations at this time• Metformin + sulfonylurea + insulin• Sulfonylurea + bedtime insulin• Lispro + glyburide

Not recommended: thiazolidinediones + insulin = HYPOGLYCEMIA

A 56-year-old overweight woman has had urinary frequency, nocturia, and dysuria for 5 days. She also reports increasing thirst.

On physical examination, her temperature is normal, she appears dehydrated, and has no costovertebral angle tenderness. Her plasma glucose concentration is 620 mg/dL. Urinalysis reveals 4+ glucose, no ketones, strongly positive protein, and 8 to 10 leukocytes per high-power field. Antibiotic therapy is begun for the urinary tract infection.

Which one of the following therapies is the most appropriate at this time?

( A ) Sulfonylurea( B ) Diet and exercise program( C ) Insulin( D ) Metformin( E ) α-Glucosidase inhibitor

Critique (Correct Answer = C)

The therapeutic goals in this patient are to alleviate symptoms and control hyperglycemia. When a newly diagnosed patient has symptoms, evidence of a urinary tract infection and markedly elevated plasma glucose concentration, treatment with insulin is the best assurance that symptoms will resolve and that the infection will respond readily to appropriate therapy. Hospitalization is usually not warranted unless ketoacidosis or severe dehydration and hypotension are present. Some patients will respond to oral agents, such as metformin, but that response may be slow and insufficient to alleviate symptoms. After prolonged periods of markedly elevated glucose, the response to sulfonylureas is blunted as the beta cells of the pancreas produce little or no insulin because of the glucose toxicity. After 6 to 8 weeks of good glycemic control effected by insulin, therapy may be switched to an oral agent if the patient prefers. A benefit of tight glycemic control with intensive insulin therapy in such patients is the reversal of glucose toxicity, with the improvement of both insulin sensitivity and insulin secretion. α-Glucosidase inhibitors like acarbose, reduce postprandial hyperglycemia by delaying glucose absorption, but do no affect glucose utilization or insulin secretion. They are less potent agents and therefore would not be the correct agents to use to control her hyperglycemia.

Every patient with newly diagnosed diabetes mellitus should be offered an educational program that emphasizes the importance of diet and exercise. In symptomatic patients with this severe a degree of hyperglycemia, diet and exercise are inadequate to achieve the desired goals.

DKA HONC

Glucose 300-600 600-1200

Sodium 125-135 135-145

Potassium Nml to increased Nml

Magnesium Nml Nml

Phosphate Decreased Nml

CRE Nml to slight increased Mod increased

Ketones ++++++ -----

HCO3 <15 meq/l Nml to slightly decreased

Ph 6.8-7.3 >7.3

Anion Gap Increased Nml to increased

Initial Visit

History Physical – don’t forget eye exam and

foot exam (monofilament) Labs

Fasting Chem 7, Hgb A1C (not diagnostic!!!), fasting lipids, LFTs, UA with urine microalbumin, TSH

ECG

Prevent, Monitor, Manage and Educate Diet, exercise, weight control Smoking cessation Blood pressure (strict BP goals) Lipids (remember DM = CAD equivalent) Renal function Annual eye exam Podiatric/orthopedic exam Pneumovax, influenza vaccine

Prevent, Monitor, Manage and Educate Weekly, monthly follow up Diabetic education!!!

Medication administration Blood glucose monitoring Lifestyle changes

HgbA1C q 3-6 months along with any other labs

Support groups Websites (www.diabetes.org) Your encouragement, support

Diabetic Complications Coronary Artery Disease Acute Complications

DKA, HONK Hyperglycemia, Hypoglycemia

Long Term Complications CAD Peripheral Vascular Disease Diabetic Retinopathy

• Nonproliferative, proliferative Diabetic Nephropathy Diabetic Neuropathy

• Peripheral Sensory• Cardiovascular Autonomic• Gastrointestinal Autonomic• Erectile dysfunction

Diabetic Foot• Dr. Attinger

Cardiovascular Disease

BP goal < 130/80 Lipids: LDL < 100, TG < 150, HDL > 40/50 Statins for DM patients > 40 to achieve LDL reduction of

30% regardless of baseline (Heart Protection Study) Aspirin for primary or secondary prevention Smoking cessation Cardiac stress testing

any symptoms – typical or atypical abnormal EKG h/o peripheral vascular disease Sedentary lifestyle, age > 35 and plans to exercise > 2 risk factors (dyslipidemia, HTN, smoking, FH,

micro/macroalbuminuria)

Peripheral vascular disease/Foot care

Examine feet at every visit

Check pedal pulses Check skin and

nails Vibrations sense,

monofilament exam Recommend

podiatry

Retinopathy

Optimal glycemic and BP control can substantially reduce the risk and progression of DM retinopathy

Annual screening for most Laser therapy can reduce the risk of vision

loss in patients with high risk characteristics (disc neovascularization or vitreous hemorrhage with any retinal neovascularization)

Retinopathy

Background retinopathy

Vision normal Microaneurysms Hemorrhages Exudates May see a

macular star

Pre-proliferativeRetinopathy

Cotton-wool spots Venous dilatation Large deep

hemorrhages

Diabetic maculopathy

Retinopathy in macula

Causes reduced visual accuity and blindness and requires urgent laser therapy

Proliferative retinopathy

Retinal neovascularization

Vitreous hemorrhage

Fibrosis and retinal detachment

A 41-year-old man with type 1 diabetes mellitus has a funduscopic examination during a routine office visit. The findings are seen on the funduscopic photograph. What does the funduscopic photograph on the left show?( A ) Diabetic background retinopathy( B ) Diabetic proliferative retinopathy( C ) Diabetic macular degeneration( D ) Papilledema

Nephropathy

25-30% of patients with diabetes develop nephropathy Can be prevented or delayed with tight glycemic and BP

control All pts need screening UA

If UA shows proteinuria then needs 24 hour urine protein

If UA negative check for microalbuminuria (30-299 mg/24hr) annually

• Spot albumin:Cr ratio vs. 24hr albumin measurement Albuminuria is associated with a 4-8 fold increased

cardiovascular risk If albuminuria present pt should be started on ACE

inhibitor/ARB and glycemic control should be tightened.

Neuropathies Peripheral sensory neuropathy

Symmetrical distal dysasthesias and pain Initially loose vibration sense Tx with tricyclics and gabapentin

Autonomic neuropathy Presents with orthostatic hypotension, absent

normal variation of heart rate with breathing Tachycardia and sudden death Treat orthostatic hypotension with

Fludrocortisone and Midodrine

Neuropathies II

GI autonomic neuropathies Gastroparesis

• Nausea, vomiting, bloating and GERD Diarrhea

• Especially nocturnal diarrhea Treatment: Metoclopramide (Reglan)

Erectile dysfunction > 50% of men with DM have erectile

dysfunction Typically unable to achieve both nocturnal and

morning erections (distinguishes arousal problem from vascular problem)

Treatment: Sildenafil, but avoid in pts with cardiovascular disease or on nitrates.

Neuropathies III

MononeuropathiesCan develop wrist drop (radial nerve),

foot drop (sciatic nerve) or CN III palsyProbably related to damage to

microvascular supply to nerve Diabetic Amyotrophy

Pain, atrophy and fasciculations of the limb girdle muscles.

A 70-year-old woman has developed weakness and numbness of her legs and arms during the past 8 months. The symptoms began with tingling in her feet. Later, severe weakness gradually developed. For 2 years, she has been taking oral hypoglycemic agents to treat diabetes.

On physical examination, the patient has a pulse rate of 70/min and a blood pressure of 120/85 mm Hg. She cannot rise from her chair without pushing off with her arms. She has moderately severe weakness (3/5) of the thigh and lower leg muscles. There is little movement remaining in her feet and toes (1/5). Her hands are also very weak (2/5). She has no deep tendon reflexes in her lower extremities. Vibration sensation and position sense are slightly reduced at the toes and malleoli. Pinprick and touch sensations are normal. Her toes do not move in response to plantar stimulation. Fasting plasma glucose level is 95 mg/dL; the 2-hour postprandial plasma glucose level is 125 mg/dL. HgbA1C is 5.6%.

Which of the following is the most likely diagnosis? ( A ) Spinal cord tumor

( B ) Polymyositis( C ) Hemispheric stroke( D ) Chronic inflammatory demyelinating polyneuropathy

Critique (Correct Answer = D)

This woman has chronic inflammatory demyelinating polyneuropathy predominantly affecting motor fibers, causing significant limb paralysis. The combination of greater distal than proximal muscle weakness, areflexia, and distal loss of vibration sense is characteristic of a peripheral polyneuropathy that affects mostly myelinated fibers. A muscle disease such as polymyositis would cause greater proximal than distal weakness. A spinal cord lesion would not be symmetric, and sensory loss would not be limited to vibration. A hemispheric stroke would produce unilateral signs and symptoms. The differential diagnosis is between a demyelinating polyneuropathy and a diabetic peripheral polyneuropathy.

Diabetic peripheral polyneuropathy is most often a rather mild disorder that causes some decreased sensation in the toes and feet and a loss of ankle reflexes. More severe polyneuropathies do occur, especially in long-standing diabetes, especially if diabetic control is poor. This woman had very mild diabetes that is well controlled. A rapidly progressive, severe, paralyzing polyneuropathy explained by diabetes would be extremely rare in her circumstances. Chronic inflammatory demyelinating polyneuropathy is a relatively common polyneuropathy presumed to be of an autoimmune basis in which proximal and distal weakness and areflexia are common. Usually sensory loss is limited to vibration and position sense, sensory functions mediated by large myelinated fibers within peripheral nerves. Some have thought of this disorder as a kind of chronic Guillain-Barré syndrome. The history and physical examination presented are typical of chronic inflammatory demyelinating polyneuropathy. Electrophysiologic studies will document widespread decrease in motor and sensory nerve conduction velocities indicative of a demyelinating polyneuropathy.

Summary• GLYCEMIC CONTOL (GOALS)

• Pre-prandial glucose: 80-120• 2 hour post prandial glucose: <160• Pre-bed glucose: 100-140• HbA1c <6.5 - 7%

• REVIEW REGIMEN• Insulin vs. oral hypoglycemics

• MONITORING• HbA1c • Urine microalbumin• Lipid profile LDL < 100, TG<150, HDL>50

• CLINICAL EXAM• Fundoscopy• Foot exam• Cardiac and peripheral pulses• BP <130/80

• EDUCATION• Smoking• Diet• Exercise• Consider Aspirin unless contraindication