Diagnosis and Management of Type 2 Diabetes

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Diagnosis_and_Management_of_Type_2_DiabetesSteve V. Edelman, MD

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....

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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, á-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.

DCMS20_Edelman15-Tab9

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.

DCMS20_Edelman15-Fig3

Mononeuropathy

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)

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