Best Dx/Best Rx: Type 2 Diabetes Mellitus

From: Subject: Best Dx/Best Rx: Type 2 Diabetes Mellitus Date: Wed, 3 Jun 2009 21:14:12 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0149_01C9E490.3DE1C6C0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0149_01C9E490.3DE1C6C0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0902.htm Best Dx/Best Rx: Type 2 Diabetes Mellitus

Type 2 = Diabetes=20 Mellitus

Matthew C. Riddle, M.D.
Oregon = Health and=20 Science University School of Medicine
Saul=20 Genuth, M.D., F.A.C.P.
Case Western Reserve University = School of=20 Medicine

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

Definition/Key Clinical=20 Features

A metabolic disorder characterized by = hyperglycemia,=20 insulin resistance, and relative insulin insufficiency =

Classic Features (Relatively Uncommon)=20

Polyuria=20
Polydipsia=20
Polyphagia=20
Weight loss

Typical=20 Presentations

Hyperglycemia per screening tests
Peripheral neuropathy
Weakness=20
Blurred vision
Central obesity
Recurrent infections (e.g., vaginitis) =

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Differential = Diagnosis

Type 1: insulin deficiency, beta cell = destruction=20
Type 2: insulin resistance and variable = insulin=20 deficiency
Endocrine dysfunction (e.g., Cushing syndrome, = acromegaly)

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Best=20 Tests

Plasma glucose, randomly sampled, > 200 = mg/dl with=20 symptoms or fasting plasma glucose > 126 mg/dl with or without = symptoms=20
Confirm with second test

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Best=20 Therapy

Nutritional Therapy = and=20 Exercise=20

Caloric reduction to produce weight loss = (determine=20 intake reduction on basis of degree of obesity and with dietitian's = help)=20
Diet < 30% total fat, < 10% saturated = fat, <=20 10% polyunsaturated fat, 10%=9615% monounsaturated fat, 10%=9620% = protein, 50%=9655%=20 carbohydrate=20
Addition of high-fiber foods
Awareness of carbohydrates to limit = postprandial plasma=20 glucose elevation
Gradual increase in aerobic exercise =

Pharmacologic Therapy

American Diabetes Association goals
- Preprandial capillary whole blood glucose = levels:=20 90=96130 mg/dl
- Postprandial peak capillary whole blood = glucose=20 levels: < 180 mg/dl=20
- Hemoglobin A_1c (HbA_1c) = level 7%=20 or lower if feasible without undue risk of hypoglycemia =
Begin with monotherapy; if response is not = satisfactory=20 by 3=966 mo, add additional drug
Sulfonylureas (SUs): first choice for = normal-weight=20 patients; side effects are hypoglycemia, weight gain
- Glipizide, extended release (XL)=20
  - Dose: lowest usual dosage, 2.5 mg q.d.; = maximum=20 effective dosage, 5 mg q.d.
  - Cost/mo: $11
- Glimepiride=20
  - Dose: lowest usual dosage, 1 mg q.d.; = maximum=20 effective dosage, 4 mg q.d.=20
  - Cost/mo: $15
Non-SU secretagogues; short half-life; take = with meals=20 to avoid hypoglycemia; side effects are hypoglycemia, weight gain =
- Repaglinide=20
  - Dose: lowest usual dosage, 0.5 mg q.d.; = maximum=20 effective dosage, 4 mg t.i.d.=20
  - Cost/mo: $222
- Nateglinide=20
  - Dose: lowest usual dosage, 60 mg q.d.; = maximum=20 effective dosage, 120 mg t.i.d.=20
  - Cost/mo: $115
α-Glucosidase inhibitors: monotherapy for = postprandial=20 hyperglycemia; must be taken at start of meals; side effects are = flatulence,=20 diarrhea
- Acarbose
  - Dose: lowest usual dosage, 25 mg t.i.d.; = maximum=20 effective dosage, 100 mg t.i.d.=20
  - Cost/mo: $87
- Miglitol
  - Dose: lowest usual dosage, 25 mg t.i.d.; = maximum=20 effective dosage, 100 mg t.i.d.=20
  - Cost/mo: $81
Biguanides
- Metformin: first choice for obese patients;=20 contraindicated in renal insufficiency; side effects are nausea, = diarrhea,=20 lactic acidosis (rare)=20
  - Dose: lowest usual dosage, 500 mg q.d.; = maximum=20 effective dosage, 1,000 mg b.i.d.=20
  - Cost/mo: $56
- Metformin extended release=20
  - Dose: lowest usual dosage, 500 mg q.d.; = maximum=20 effective dosage, 1,000 mg b.i.d.=20
  - Cost/mo: $48
Thiazolidinediones: insulin sensitizers; side = effects=20 are weight gain, edema, heart failure (rare)=20
- Pioglitazone
  - Dose: lowest usual dosage, 15 mg q.d.; = maximum=20 effective dosage, 45 mg q.d.=20
  - Cost/mo: $180
- Rosiglitazone
  - Dose: lowest usual dosage, 2 mg q.d.; = maximum=20 effective dosage, 4 mg b.i.d.=20
  - Cost/mo: $211 =

Combination Oral Therapy

Use same drugs as with monotherapy, beginning = with the=20 lowest suggested dose of each
- Sulfonylurea + metformin
- Sulfonylurea + thiazolidinedione
- Metformin + thiazolidinedione
- Metformin + repaglinide
- Repaglinide + thiazolidinedione
- α-Glucosidase inhibitors + any other = drug=20
- Sulfonylurea + metformin + thiazolidinedione =
- Metformin + thiazolidinedione + repaglinide = or=20 nateglinide=20
- Insulin + any other drug =

Insulin Therapy=20

One daily injection of long-acting insulin = (NPH,=20 glargine, or detemir)=20
- Dose: 10 U or 0.15 U/kg initially; increase = by 2 U=20 once or twice weekly until fasting glucose ≤ 120 mg/dl; or = increase by 6=968 U=20 weekly until fasting glucose ≤ 140 mg/dl, then increase by = 2=964 U weekly=20 until fasting glucose ≤ 120 mg/dl
Regular or rapid-acting insulin before meals = if=20 postprandial glucose not controlled=20
- Take regular insulin 30 min before = meal=20
- Take rapid-acting insulin just before or = just after=20 meal

Injectable = Gastrointestinal=20 Hormone Agents=20

Pramlintide: if optimal glycemic control not = achieved=20 with insulin and HbA_1c < 9%=20
- Dose: 30=9660 =B5g initially, with slow = titration to 120=20 =B5g if needed=20
- Reduce preprandial insulin by half =
Exenatide: for patients taking a sulfonylurea, = metformin, or both; hypoglycemia can occur with sulfonylurea=20
- Dose: 5 =B5g b.i.d. initially, increase to = 10 =B5g b.i.d.=20 after 1 mo

Oral Dipeptidyl Peptidase IV = Inhibitor=20

Sitagliptin: approved for use as monotherapy = and as=20 combination therapy with metformin or a thiazolidinedione
- Blocks inactivation of GI peptide = hormones=20
- Dose: 100 mg/day; 50 or 25 mg/day in = patients with=20 moderate or severe renal insufficiency =

Blood Glucose Self-Testing

Once daily with stable control=20
Once per insulin injection=20
Postprandially with rapid-acting or regular = insulin=20
When symptoms of hypoglycemia occur =

HbA_1c Measurement

At least every 6 mo

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Best References

DeWitt DE, et al: JAMA 289:2254, 2003 [PMID=20 12734137]

Gerich JE: Arch Intern Med 163:1306, 2003 [PMID=20 12796066]

Knowler WC, et al: N Engl J Med 346:393, 2002 = [PMID=20 11832527]

Nathan DM, et al: Diabetologia 49:1711, 2006 = [PMID=20 16?02130]

Turner RC, et al: JAMA 281:2005, 1999 [PMID=20 10359389]

Matthew C. Riddle, M.D., has received = honoraria for=20 consulting or speaking, or research grant support from Amylin, = GlaxoSmithkline,=20 Lilly, Novo-Nordisk, Sanofi-Aventis, and Pfizer. Saul Genuth, M.D., = F.A.C.P.,=20 has no commercial relationships with manufacturers of products or = providers of=20 services discussed in this module.=20

February=20 2007