A 65-year-old man comes to the office for follow-up monitoring of type 2 diabetes mellitus. He was diagnosed with diabetes 7 years ago and follows a strict diet to control his blood sugar level. The patient takes no medications. Blood pressure is 139/88 mm Hg and pulse is 70/min. Physical examination shows decreased lower-extremity sensation with a 10-g monofilament. His most recent hemoglobin A1c is 7.4% (normal, <5.6%). Serum creatinine is 1.0 mg/dL and serum potassium is 3.8 mEq/L. Further laboratory evaluation reveals increased urinary albumin excretion, but a conventional urinalysis is within normal limits. In addition to starting antihyperglycemic treatment, which of the following is the best pharmacotherapy for this patient?
Show Explanatory Sources
This patient has diabetes mellitus complicated by neuropathy (decreased lower-extremity sensation) and nephropathy (increased urinary albumin excretion). Moderately increased albuminuria (also called microalbuminuria) is defined as urine albumin loss of 30-300 mg/day and is an early indication of diabetic nephropathy (DN). Microalbuminuria cannot be detected by standard dipstick urinalysis; only albumin excretion >300 mg/day (severely increased albuminuria) can be detected by conventional urinalysis. If left untreated, albuminuria is followed by progressive worsening of renal function leading to end-stage renal disease.
The progression of DN can be reduced by glycemic and blood pressure control. In addition, progression can be slowed by use of ACE inhibitors (eg, lisinopril) or angiotensin II receptor blockers. Early DN is characterized by elevated glomerular filtration pressure; angiotensin II further increases glomerular pressure by selective vasoconstriction of the efferent arteriole. Blockade of this angiotensin effect lowers glomerular pressure. Although ACE inhibitors decrease glomerular filtration in the short term, chronic use decreases albumin excretion and slows progression to overt renal failure. This benefit is independent of effects on systemic blood pressure and can also be seen in nonhypertensive patients.
(Choice A) Nondihydropyridine calcium channel blockers (eg, diltiazem, verapamil) decrease proteinuria, but this effect is not seen with dihydropyridine agents (eg, amlodipine, nifedipine). Although blood pressure control is important in patients with diabetes, lisinopril is more beneficial for preventing progression of nephropathy.
(Choices B and C) Carvedilol is a nonselective beta- and alpha-adrenergic blocker used in hypertension and congestive heart failure. Eplerenone is a mineralocorticoid (aldosterone) antagonist that is also used in congestive heart failure. These agents have no specific role in the management of DN.
(Choice D) Hydrochlorothiazide is an effective antihypertensive agent. However, it also causes hyperglycemia and may be associated with worsened glucose control in diabetic patients. ACE inhibitors are preferred over thiazides for first-line treatment.
(Choice E) Isosorbide dinitrate is an intermediate-acting nitrate used in the treatment of stable angina pectoris. It has no role in the management of DN.
(Choice G) Alpha-1 blockers (eg, doxazosin, prazosin, terazosin) are useful for treatment of hypertension and benign prostatic hyperplasia but are not recommended as monotherapy for hypertension due to an increased risk of cardiovascular events.
Educational objective:
The risk of progression of diabetic nephropathy in patients with proteinuria can be reduced by appropriate glycemic and blood pressure control. ACE inhibitors and angiotensin II receptor blockers are the preferred antihypertensive agents due to their antiproteinuric effects, which are independent from their effects on systemic blood pressure.