Applied Evidence

Optimizing combination therapy for type 2 diabetes in adolescents and adults: A case-based approach

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Type 2 diabetes in adults

CASE 2 Woman with chronic diabetes

A 60-year-old woman presents for her annual checkup complaining of weight gain, fatigue, and tingling in her feet. Her recent history includes recurrent urinary tract and yeast infections. When initially diagnosed with type 2 diabetes 5 years ago, she had been counseled to increase activity to reduce weight; however, she had been unable to maintain consistent effort. She is 5 ft 4 in tall and weighs 230 lb (BMI, 39.5 kg/m2) with a waist circumference of 40 in. Her weight has fluctuated, but she has had a net gain of 30 lb over the last 5 years. Education and lifestyle modification efforts were reinitiated 1 year ago. The patient is a smoker and has cut her habit to 5 cigarettes per day. Her A1C and total cholesterol levels 1 year ago were 7.8% and 203 mg/dL, respectively. The patient also had cataract surgery 1 year ago. Her current medications include lisinopril 40 mg/d, furosemide 40 mg bid, and rosiglitazone 4 mg/d. She performs SMBG infrequently.

On examination, her BP is 125/72 mm Hg. A random fingerstick blood glucose test shows 210 mg/dL. She exhibits normal monofilament sensation, vibratory sensation, and ankle jerks. She also shows signs of mild pedal edema with no foot lesions and normal pedal pulses.

There are a number of signs suggesting this patient’s diabetes is inadequately controlled, including her complaints of fatigue and repeated yeast infections. Poorly controlled diabetes also is associated with peripheral neuropathy, which may manifest as a tingling sensation or numbness that begins in the feet and moves upward; however, her physical examination is negative for neuropathy.36 A random blood glucose level is of limited value and should not be relied upon as an indicator of the patient’s glycemic status. An A1C measurement is overdue for this patient and will reflect her overall glycemic control in recent months.

A total cholesterol level is rarely adequate for clinical decision making and thus a follow-up lipid profile is warranted. Her BP is well controlled with her current antihypertension regimen. The ADA guidelines recommend adequate treatment of hypertension (target BP, <130/80 mm Hg) in diabetic patients and suggest use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) because, in addition to their antihypertensive effects, these agents may provide renal benefits for patients with albuminuria or renal insufficiency.20 More typically, a thiazide rather than a loop diuretic is used in combination with an ACE inhibitor (or another antihypertensive drug class) as treatment for hypertension but, since the patient’s BP is well controlled with her current regimen and she has mild pedal edema, the loop diuretic may be maintained.

Her weight gain and peripheral edema may in part be due to rosiglitazone treatment. Edema that is not caused by congestive heart failure is not a contraindication for glitazone use but requires close monitoring and should lead to a consideration of alternate therapy.25

CASE 2 Laboratory assessment

The patient’s glycemic indices are: FPG, 184 mg/dL; A1C, 9.4%; postprandial glucose (PPG), 311 mg/dL. A random urine sample reveals microalbuminuria (protein/creatinine, 38 μg/mg). Her serum creatinine is 1.6 mg/dL. Her lipid panel reveals: total cholesterol, 271 mg/dL; LDL cholesterol, 165 mg/dL; HDL cholesterol, 35 mg/dL; and triglycerides, 355 mg/dL. Liver function tests are within normal limits. Further evaluation indicates that she does not have congestive heart failure.

The laboratory results indicate very poor control of overall and postmeal glucose levels. In addition, she now has microalbuminuria. Although poor adherence with therapy should be ruled out, the loss of control with a previously effective therapy is not unusual and underscores the progressive nature of diabetes.

Collectively, this patient’s poor glycemic control, dyslipidemia and central obesity, place her at a very high risk for CVD.37

CASE 2 Therapy adjusted

Glimepiride 4 mg/d is added to the rosiglitazone; in addition, atorvastatin 20 mg/d and fenofibrate 160 mg/d are prescribed. Lifestyle modifications (eg, dietary changes, exercise, smoking cessation) are reinforced, and the patient is referred to a certified diabetes educator.

The comprehensive approach taken for this patient is consistent with that advocated by the results in the Steno-2 Study. Gaede et al1 demonstrated that a targeted, intensified, multifactorial, interventional approach to improving macrovascular and microvascular risk factors in patients with type 2 diabetes reduces the risk of macrovascular and microvascular diabetic complications by about 50% compared with conventional treatment.1 Specifically, patients receiving intensive therapy had a significantly lower risk of CVD, nephropathy, retinopathy and autonomic neuropathy.1 Intensive, multifactorial therapy involved dietary interventions; a consistent exercise program; smoking cessation; use of ACE inhibitors (or ARBs for patients intolerant to ACE inhibitors) for renal benefits and combined with diuretics and other agents, if necessary, to treat hypertension; lipid-lowering therapy to treat hyperlipidemia (statins, plus fibrates for isolated cases of hypertriglyceridemia); pharmacotherapy for glucose control; daily vitamin-mineral supplements; and daily aspirin as a secondary measure for the prevention of CVD.

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