Best Dx/Best Rx: Obesity

From: Subject: Best Dx/Best Rx: Obesity Date: Wed, 3 Jun 2009 21:42:46 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_021D_01C9E494.3BEF21B0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_021D_01C9E494.3BEF21B0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0310.htm Best Dx/Best Rx: Obesity

Obesity

Jonathan Q. Purnell, M.D. Oregon Health and = Science=20 University

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key=20 Clinical Features

Obesity: abnormal accumulation of body fat in = proportion=20 to body size=20
Increased risk of comorbid disorders=20
- Hypertension=20
- Type 2 diabetes
- Cardiovascular disease=20
- Hyperlipidemia
- Gallstones
- High uric acid levels
- Hepatic steatosis
- Osteoarthritis=20
- Obesity hypoventilation
- Sleep apnea
- Possibly, some types of cancer =
Overweight persons have a body-fat proportion=20 intermediate between normal and obese=20
Risk of comorbid conditions increases with = body mass=20 index (BMI) and waist circumference

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Differential=20 Diagnosis

Hypothyroidism=20
Hypercortisolemia
Deficiencies of growth hormone or gonadal=20 steroids=20
Medications=20
- Long-term glucocorticoid treatment of = inflammatory=20 conditions=20
- Immunosuppression after = transplantation=20
- Cancer chemotherapy=20
- Intensive glycemic control with insulin, a=20 sulfonylurea, or a thiazolidinedione=20
- Neuropsychotropic drugs, particularly newer=20 antipsychotic and antiseizure medications=20

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Best=20 Tests

History=20

Obtain weight-gain history
- Childhood versus adult
- Gradual versus sudden
- Associated with head trauma or medication = use
- Rapid weight gain should lower threshold for = screening=20 for conditions in the differential diagnosis
Current and past dietary and exercise = habits=20
Evaluate for diseases for which obese patients = are at=20 higher risk=20
- Hypertension
- Impaired glucose tolerance or diabetes =
- Hyperlipidemia
- Heart disease
- Sleep apnea=20
  - Restless sleep at night
  - Snoring or observed apnea
  - Fatigue or headache upon awakening and = during the=20 daytime
  - Spontaneous daytime sleep when inactive or = while=20 driving

Physical=20 Examination=20

BMI calculation; BMI =3D body weight (in = kilograms)=20 divided by height (in meters) squared=20
- Underweight: BMI < 18.5=20
- Normal: BMI =3D 18.5=9624.9=20
- Overweight: 25=9629.9=20
- Obese: BMI ≥ 30
Fat distribution=20
- Increased relative risk of coronary artery = disease,=20 diabetes, and hypertension if waist circumference exceeds 40 in. = (102 cm)=20 for men and 35 in. (88 cm) for women
Acanthosis nigricans
- Patches of feathery-pigmented skin = (hyperkeratotic and=20 hyperpigmented) on the extensor surfaces of the hands and elbows, in = the=20 axilla, or on the neck
- Occurs in insulin resistance and type 2=20 diabetes
Presence of xanthomata=20
- Eruptive xanthoma
  - Indicates elevated blood levels of = chylomicrons=20
- Palmar or tuberoeruptive xanthoma=20
  - Indicates type III hyperlipidemia =
- Tendon xanthoma=20
  - Indicates familial = hypercholesterolemia=20
Cushing syndrome=20
- Round facies=20
- Facial plethora
- Supraclavicular fat pad enlargement
- Purplish striae
- Thin (=93cigarette paper=94) skin
- Muscle weakness
Hypothyroidism=20
- Doughy skin
- Loss of lateral eyebrows
- Pretibial edema
- Delayed relaxation phase of reflexes=20

Laboratory Tests =

Impaired glucose tolerance=20
- Either a fasting plasma glucose level of = 100=96125 mg/dl=20 or a 2-hr glucose level of 140=96200 mg/dl after an oral glucose = tolerance=20 test
Type 2 diabetes=20
- Two fasting blood glucose measurements of = ≥ 126 mg/dl,=20 a 2-hr glucose level of ≥ 200 mg/dl during an oral glucose = tolerance test,=20 or a random glucose level of ≥ 200 mg/dl and symptoms of = diabetes=20
Screening for thyroid disease, Cushing = syndrome, and=20 deficiencies of growth hormone and sex steroids when clinically=20 indicated

Screening for = Macrovascular=20 Risk=20

Blood pressure measurements=20
ECG when appropriate=20
Fasting lipid profile=20

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Best=20 Therapy

Testing and treatment for any secondary causes = of=20 obesity and comorbid conditions
Manage with lifestyle measures for 3=966 mo; = if weight=20 loss is insufficient to lower long-term health risks, consider = pharmacologic=20 or surgical therapy=20
If BMI ≥ 30 or if BMI > 27 in patient = with=20 obesity-related risk factors (i.e., diabetes, hypertension, or=20 hyperlipidemia), consider pharmacologic therapy=20
If BMI ≥ 40 or if BMI > 35 in patient = with=20 obesity-related risk factors, refer for surgery=20
Goal for pharmacologic or surgical treatment, = together=20 with lifestyle measures: sustained loss of ≥ 5% of initial body = weight=20

Nonmedical (Lifestyle) = Therapy=20

Diet Modification=20

Caloric restriction=20
- Without additional interventions such as = exercise or=20 pharmacologic therapy, ≥ 95% of initially lost weight will be = regained=20 within 5 yr
Dietary-fat restriction=20
- Restriction of dietary fat to 25%=9630% of = calories=20 results in significant but modest weight loss; response is highly=20 varied
Dietary-carbohydrate changes=20
- Increasing dietary carbohydrate intake while = lowering=20 total fat intake results in modest weight loss (~ 2=964 kg) in = overweight and=20 obese persons if the additional carbohydrates come from fruits, = vegetables,=20 and grain products
- Can help sustain weight loss after a period = of caloric=20 restriction=20
- Severe carbohydrate restriction (< 25 = g/day) may=20 lead to modest spontaneous weight loss by inducing ketogenesis, but=20 sustainability of weight loss and long-term health outcomes are=20 unclear
Dietary-protein changes=20
- Protein intake should be limited to ~ = 10%=9615% of daily=20 calories=20
- Obese patients can have significantly = greater weight=20 loss on a high-protein diet (~ 30% total calories) than on a regular = or a=20 low-fat, high-carbohydrate diet, but potential adverse outcomes have = not=20 been adequately studied=20
- High protein intake may be associated with = intestinal=20 cancers, bone disease, and renal disease=20
- High protein intake increases glomerular = filtration=20 rate, which may harm patients with existing renal disease or = diabetes=20

Exercise=20

Weight loss of 1=964 kg (2.2=968.8 lb) over 1 = yr in=20 randomized, controlled studies=20
Can help sustain weight loss after a period of = caloric=20 restriction=20
American College of Sports Medicine recommends = a minimum=20 exercise level of 1,000 kcal/wk for reducing body weight, but 2=963 = times that=20 level is more effective for significant, sustained weight loss=20
Should be encouraged because of health = benefits=20 attributable to fitness

Combined Diet and=20 Exercise=20

Initial treatment of overweight and obese = patients=20 should include dietary-fat restriction and increased activity using=20 individualized, sustainable behavioral and lifestyle changes=20
Dietary-fat restriction and exercise can = improve lipid=20 levels, increase insulin sensitivity, and reduce risk of progression = of=20 cardiovascular disease and of onset of type 2 diabetes=20
If lifestyle measures are not effective, = medical and=20 surgical treatments can be considered

Pharmacologic Therapy=20

Effective in achieving weight loss of up to = 10% of=20 initial body weight for at least 2 yr=20
In most studies, patients began a hypocaloric = diet=20 (daily caloric intake reduced by 500=961,000 kcal) before drug = treatment=20
Weight loss with obesity agents varies = considerably,=20 usually < 10% of baseline weight=20
Weight loss is greatest during the first 3=966 = mo,=20 followed by a plateau at a new lower weight even with continued = therapy=20
Rapid weight regain toward baseline follows=20 discontinuance of medication=20
Treatment should be continued indefinitely = unless the=20 weight is regained or significant side effects develop =

Agents Approved for Short-term Use=20

Phentermine=20
- Inhibits appetite=20
- Average weight loss, 8.7 kg (19.2 lb) =
- May cause anxiousness, insomnia, = palpitations, dry=20 mouth, vasospasm, psychosis, and ischemic events
- May be used long term if weight loss = sustained=20
- Dose: 30 mg resin, or 15 or 37.5 mg tablets; = doses=20 > 37.5 mg not recommended
- Cost/mo: $23 =

Agents Approved for Long-term Use=20

Sibutramine=20
- Inhibits appetite=20
- Average weight loss, 7.0 kg (15.4 lb) =
- Associated with improvements in lipid levels = and=20 glycemic control in diabetes=20
- May cause dry mouth, constipation, insomnia, = palpitations, and headache=20
- Raises blood pressure and pulse rate, which = should be=20 monitored; contraindicated in patients with cardiovascular disease, = heart=20 failure, arrhythmia, or stroke=20
- Dose: 5=9615 mg/day=20
- Cost/mo: $110
Orlistat=20
- Reduces fat absorption=20
- When combined with a calorie-restricted = diet, results=20 in an average weight loss of 7.24=9613 kg (16 to 28.7 lb) and = significant=20 reduction in levels of total and LDL cholesterol=20
- Blood pressure and insulin levels decrease = and=20 glycemic control improves with weight loss=20
- Side effects include abdominal discomfort, = flatus,=20 fecal urgency, oily spotting, and fecal incontinence=20
- To minimize side effects related to fat = malabsorption,=20 candidates for orlistat treatment are first placed on a = 30%-fat=96restricted=20 diet=20
- Contraindicated in patients with existing=20 malabsorptive states=20
- Patients should take a daily multivitamin = supplement=20 during therapy=20
- Dose: 250 mg with each meal=20
- Cost/mo: $260 =

Non=96FDA-Approved Medical Therapy for = Obesity=20

Selective serotonin reuptake inhibitors =
- Weight loss is modest and short-lived =
Bupropion plus modest daily caloric = restriction=20
- Can produce weight loss=20
- Contraindicated in patients with seizures, = anorexia=20 nervosa, and bulimia=20
- Dose: 300=96400 mg/day=20
- Cost/mo: $134
Growth hormone, sex steroids=20
- No clear benefit for obesity unless there = are clear=20 hormonal deficiencies =

Medications Associated with Weight Gain: Replace with = Alternative=20 Agents=20

Systemic steroids (glucocorticoids)
- Alternatives=20
  - Asthma: inhalers=20
  - Cancer chemotherapy: = non=96glucocorticoid-based=20 regimens=20
  - Rheumatoid arthritis: methotrexate and = remitting=20 agents
Antidiabetic drugs (insulin, sulfonylureas,=20 thiazolidinediones)
- Alternatives=20
  - Metformin=20
  - Acarbose
Antiepileptic drugs (gabapentin, valproic = acid)
- Alternatives=20
  - Lamotrigine=20
  - Topiramate
Antipsychotic agents (clozapine, olanzapine,=20 risperidone, sertindole)=20
- Alternatives=20
  - Haloperidol=20
  - Ziprasidone
Antidepressants (tricyclic antidepressants, = monoamine=20 oxidase inhibitors, mirtazapine)
- Alternatives
  - Bupropion=20
  - Nefazodone=20
  - SSRIs=20
  - Venlafaxine =

Bariatric Surgery=20

Can produce weight loss to up to 30% of = initial weight=20 for at least 5 yr=20
Best therapy to reverse or prevent type 2 = diabetes and=20 sleep apnea=20
Improvements in hypertension and lipid levels = more=20 closely related to amount of weight lost=20
Anatomically irreversible in most cases =
Potentially high postoperative complication = rate,=20 including infections, wound complications, and pulmonary = symptoms=20
Perioperative death rates, 0.2%=961.3%; = complication=20 rates, 13%=9636%

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Best References

Bray GA: J Clin Endocrinol Metab 89:2583, 2004 = [PMID=20 15181027]

Buchwald H, et al: JAMA 292:1724, 2004 [PMID=20 15479938]

Schwartz MW, et al: Nature 404:661, 2000 [PMID=20 10766253]

Snow V, et al: Ann Intern Med 142:525, 2005 [PMID = 15809464]

The author has served as a consultant = for=20 Amylin Pharmaceuticals, Inc.

May 2006