[acb-diabetics] Diagnosis and Management of Type 2 Diabetes

[Patricia LaFrance-Wolf]

Diagnosis_and_Management_of_Type_2_DiabetesSteve 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....


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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, 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.

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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