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Diagnosis and Management of Type 2 Diabetes, 10th Edition, Ch 15, Pt 4

Feb 14, 2011
Long-Term Complications and Treatments


Steve V. Edelman, MD
Robert R. Henry, MD

Microvascular Complications (cont’d)

Treatment for Diabetic Nephropathy


Treatment is aimed at early detection and prevention, focusing specifically on improving glycemic control, aggressively treating hypertension (e.g., with ACE inhibitor or ARB therapy and other agents as necessary), and restricting protein intake. If proteinuria is persistent or progressive, hypertension does not respond to treatment, or serum creatinine continues to be elevated, a nephrologist should be consulted. There is also evidence that treating an elevated LDL cholesterol level and taking antioxidants such as vitamin E and C, may be beneficial to the diabetic kidney….

Improving Glycemic Control

Considerable evidence supports the importance of optimizing glycemic control in delaying the development and slowing the progression of diabetic nephropathy. In the DCCT and UKPDS, intensive metabolic control was associated with a decrease in the development of microalbuminuria and clinical-grade proteinuria in patients with Type 1 and Type 2 diabetes. The benefits of improved glycemia appear to be greatest before the onset of macroalbuminuria; once overt diabetic nephropathy has developed, improved glycemia has little beneficial effects on the progression of renal disease.

Research has revealed a glycemic threshold for developing microalbuminuria, establishing an A1c level of <7% (normal is 4% to 6%) as the new glycemic goal, whereas previously it was <8%. The risk of developing microalbuminuria is substantially reduced at <7%.

Treating Hypertension

Controlling hypertension through aggressive therapeutic intervention can reduce proteinuria and considerably delay the progression of renal insufficiency. ACE inhibitors and ARBs offer effective antihypertensive effects in addition to significant delaying of the progression of diabetic nephropathy to ESRD. ACE inhibitors and ARBs decrease proteinuria by minimizing efferent glomerular vasoconstriction and reducing glomerular hyperfiltration. In cases where the glomerular flltration rate has already declined, ACE inhibitors also can partially reverse or prevent a further decrease. ACE inhibitors and ARBs should be considered as first-line therapy in all normotensive and hypertensive patients with diabetes who have micro-albuminuria or macroalbuminuria. ARBs (losartan, valsartan, irbesartan, candesartan) do not cause cough.

When blood pressure cannot be adequately controlled with the maximum dose of an ACE inhibitor or ARB, additional antihypertensive medications may be needed, such as CCBs, α-blockers (indapamide) and centrally acting agents (clonidine patch). Patients with renal insufficiency and hypertension may be given a diuretic as part of the antihypertensive regimen because of related sodium and fluid retention; a loop diuretic usually is necessary if the creatinine level exceeds 2 mg/dL.

Restricting Protein Intake

Protein intake should be limited to 0.8 g/kg/day or approximately 10% of daily calories, derived primarily from lean animal and vegetable or plant sources, in patients with diabetes and evidence of nephropathy. Vegetable proteins appear to have beneficial renal effects compared with animal sources and provide an important protein supplement or substitute in low-protein diets. The value of restricting protein intake in the absence of diabetic renal disease has not been clearly demonstrated. Low-protein diets can be made more palatable with a greater variety of vegetable protein sources and increased consumption of high-fiber complex carbohydrates and monounsaturated fats.

  • Diabetic Neuropathy

The various diabetic neuropathies are one of the more common yet distressing long-term complications of diabetes, affecting 60% to 70% of patients with Type 1 and Type 2 diabetes. The categories of diabetic neuropathy are shown in Table 15.9. As discussed below, there are several approaches to the management of specific types of diabetic neuropathy. However, there are few options for treating the underlying pathophysiology.


Therefore, the results of an 8-year observational study in Australia are of some interest. The results showed that treatment of diabetic patients with either a statin or fibrate reduced the risk of developing peripheral neuropathy by 35% and 48%, respectively. Several possible underlying mechanisms for this protective effect were suggested, including the fact that statins are mild anti-inflammatory agents and fibrates, which are peroxisome PPAR agonists, are strong anti-inflammatory agents. Although these results are encouraging, this was an observational study and not an intervention trial. Therefore, the results need to be confirmed in controlled trials and should be interpreted with some caution.

Symmetric Distal Neuropathy

These neuropathies develop most often in the lower extremities, causing numbness and tingling (pins-and needles paresthesias) usually during the night. Some patients develop painful burning and stabbing symptoms that can interfere with their quality of life and may be associated with neuropathic cachexia syndrome that includes anorexia, depression, and weight loss. Treatments that have varying degrees of effectiveness, particularly for painful neuropathies, include tricyclic antidepressants, carbamazepine, phenytoin, and counterirritants such as topical capsaicin. Aspirin should be prescribed as necessary for pain; narcotic analgesics generally should be avoided because of the risk of addiction with chronic use, however, in some cases, these drugs are necessary. Gabapentin (Neurontin) and tramadol (Ultram) are newer medications that benefit a subset of patients with painful neuropathy.

In general, treatment strategies for painful peripheral neuropathy include initial use of nonsteroidal anti-inflammatory drugs, such as aspirin and Tylenol, which can offer pain relief, especially in patients with musculoskeletal or joint abnormalities secondary to long-standing neuropathy. The tricyclic antidepressants, such as amitriptyline, remain the most commonly used drugs in the treatment of painful neuropathy. After 6 weeks of treatment, many patients report significant pain relief, independent of mood but correlating with increasing drug dosage. The topical cream capsaicin may be added to the patient’s therapeutic regimen if neuropathic pain persists in spite of treatment with maximally tolerated doses of antidepressant medication.

In an outpatient setting, approximately two thirds of diabetic patients treated with a combination of antidepressant medication and capsaicin cream experience substantial relief of neuropathic pain. In patients who experience continued pain on combination therapy, an anticonvulsant (e.g., gabapentin) or tramadol can be added as a third drug. If neuropathic pain persists despite the outlined treatment regimen, referral to a specialist, addition of a transcutaneous nerve stimulation (TENS) unit, acupuncture, or a series of local nerve blocks may be helpful, although the prognosis for pain relief in these patients is poor. A treatment flowchart for managing painful diabetic neuropathy is shown in Figure 15.3.


These neuropathies can occur in virtually any cranial or peripheral nerve, are asymmetric, and have an abrupt onset. Cranial mononeuropathies are the most common, particularly those involving the third and sixth cranial nerves, causing extraocular muscle motor paralysis and peripheral palsies. Patients can develop palsies involving the peroneal (foot drop), median, and ulnar nerves. Spontaneous recovery over 3 to 6 months is typical. Patients with diabetes are more prone to developing compression neuropathies such as carpal tunnel syndrome.

Diabetic Amyotrophy

This neuropathy often is asymmetric, is more common in men, and is often characterized by severe pain, muscle wasting in the pelvic girdle and quadriceps muscles, and mild sensory involvement. This condition usually is self-limiting, with complete recovery typically occurring in 6 to 12 months. Treatment is focused on maintaining glycemic control and symptomatic relief using physical therapy and analgesics.


Next Week: More Diabetic Neuropathies (Gastroparesis, Diabetic Diarrhea, Neurogenic Bladder, Impaired Cardiovascular Reflexes, Sexual Dysfunction, and Diabetic Foot Disorders)

You can purchase this textalt at Amazon.com, just click on this link: Diagnosis and Management of Type 2 Diabetes 10E


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