Foot Swelling in a Woman With Diabetes

Foot Swelling in a WomanWith Diabetes
During a routine office visit, a 64-year-old woman who has had type 2 diabetesfor more than 10 years complains of increased pedal edema. The edema is minimalon awakening and worsens throughout the day.

HISTORY AND REVIEW OF SYSTEMS
The patient also has stiffness in the hands and facial puffiness on awakening.There is no history of edema or congestive heart failure symptoms. A urinalysisperformed 18 months earlier showed no proteinuria; an ECG done at thesame time was also normal. She takes a sulfonylurea twice daily for glycemiccontrol and metoprolol, 50 mg/d, for hypertension.

PHYSICAL EXAMINATION
The patient is overweight at 63 kg (138.5 lb) (ideal weight for her heightis 55 kg [121 lb]). Heart rate is 90 beats per minute; blood pressure is155/92 mm Hg. Heart and lungs are normal. Neck veins are not distended,and there is no hepatojugular reflux. No abdominal distention or organomegaly.There is 2+ edema from the feet to the middle of both calves. Peripheralpulses are intact. No focal neurologic deficits; peripheral nerves are intact. Afundus examination reveals proliferative retinopathy.

LABORATORY AND IMAGING RESULTS
Hemogram is normal. Random blood glucose level is 206 mg/dL. Serum creatininelevel is 1.6 mg/dL; potassium, 4.7 mEq/L; total cholesterol, 222 mg/dL;triglycerides, 299 mg/dL; glycosylated hemoglobin, 7.9%; and albumin, 3.2 g/dL.Urinalysis shows 3+ proteinuria on dipstick. ECG findings are unchanged from18 months earlier.

Which of the following statements about this patient's diabeticnephropathy is not true?A. Better glycemic and lipid control are needed to slow the progression ofrenal disease.
B. Angiotensin-converting enzyme (ACE) inhibitors are contraindicatedbecause of the patient's elevated creatinine level.
C. In patients such as this woman, more effective blood pressure control willreduce both the progression of renal disease and the risk of cardiovascularcomplications.
D. There is ample evidence that this patient has overt nephropathy.
E. Restriction of dietary protein may help slow the progression of thispatient's renal disease.

CORRECT ANSWER: B
Type 2 diabetes is the major cause of renal failure that requiresdialysis. Nearly half of all new dialysis patients inthe United States have renal failure caused by type 2 diabetes.¹ Because the kidney is a major target organ in diabetes,a variety of strategies have been developed to monitorrenal function, diagnose and stage renal disease, andmanage renal failure in patients with diabetes.

Indicators of diabetic nephropathy. The onset andprogression of diabetic nephropathy has been wellcharacterized. Initial renal impairment is signaled by microalbuminuria,which is seen in 20% to 40% of patientswho have had diabetes for 10 to 15 years. This stage isfollowed by macroalbuminuria (more than 200 μg/min),which heralds a progressive decline in renal function (adecrease in glomerular filtration rate of 10 to 15 mL/mineach year); this decline leads in turn to renal failure andthe need for dialysis.²

There is strong evidence that this patient has overtdiabetic nephropathy (choice D). Urinalysis revealed significantproteinuria, which may even have progressed tonephrosis. Most nephrologists would recommend a 24-hour quantitation in this setting.

In some patients with complicated diabetes, additionalcauses of albuminuria, such as infection and use of certaindrugs, may be present. Nonetheless, the presence ofproliferative retinopathy in this patient essentially confirmsthat diabetic nephropathy is at least one--if not theonly--cause of the albuminuria.

Restriction of dietary protein. This has been shownto have beneficial effects and to slow the progression torenal failure in patients with type 1 diabetes. Althoughthere have been no trials of restriction of dietary proteinin patients with type 2 diabetes, many authorities use thistherapy (choice E).

Glycemic and lipid control. Various strategies, suchas glycemic and lipid control (choice A), are effective inslowing the progression of diabetic nephropathy. Twomajor studies have demonstrated a strong correlation betweenglycemic control and renal function (as well as othermicrovascular complications of diabetes).¹ Smaller studieshave found that lipid reduction has a similar correlationwith renal function, both in patients who have diabetes andin those who do not.³ In this patient, therapy must be initiatedto maintain glycosylated hemoglobin levels at lessthan 7% and to bring low-density lipoprotein cholesterollevels under 100 mg/dL.

Antihypertensive therapy. Effective blood pressurecontrol slows the progression of renal disease and reducesthe cardiovascular morbidity associated with diabetes(choice C). Blood pressure lowering also reduces the incidenceof such cardiovascular complications as congestiveheart failure.

A landmark study has demonstrated the renoprotectiveeffect of ACE inhibitors in patients with diabetic nephropathyand hypertension,⁴ and a number of subsequent studieshave confirmed the results. Indeed, ACE inhibitors are thefirst-choice antihypertensive agents for patients with diabeticnephropathy. Other agents, such as β-blockers, may beused; however, calcium channel blockers can increase proteinuriain patients with nephropathy and should be avoided.Trials are in progress to evaluate the use of ACE inhibitorsearlier in the course of diabetes (before the onset of microalbuminuria)and in normotensive patients to prevent diabeticnephropathy.

There is some risk in giving ACE inhibitors to patients,such as this woman, who already manifest a degreeof renal failure. Nonetheless, the beneficial effects of theseagents are so striking that they should be tried wheneverfeasible. Monitor patients for acute worsening of renal failureand for hyperkalemia. Start ACE inhibitor therapy at alow dosage, and measure serum creatinine and potassiumlevels 7 days after initiation or after any increase in dosage.

The small but significant elevation in this patient'screatinine level is not a contraindication to ACE inhibitortherapy at this time. Thus, choice B is false.

Outcome of this case. The patient started receivinglow-dose enalopril. At first follow-up visit, she had good bloodpressure control and an unchanged creatinine level.

References:

REFERENCES:1. Remuzzi G, Schieppati A, Ruggeneti P. Nephropathy in patients with type2 diabetes. N Engl J Med. 2002;346:1145-1151.
2. Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl JMed. 1999;341:1127-1133.
3. Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progressionof renal disease: a meta-analysis. Kidney Int. 2001;59:260-269.
4. Lewis EJ, Hunsicker LG, Bain RP, Rhode RD. The effect of angiotensin-convertingenzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456-1462.