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Diagnosis and Management of Type 2 Diabetes, 10th Edition, Ch 15, Pt 5

Feb 20, 2011
Long-Term Complications and Treatments


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

Microvascular Complications (cont’d)

This neuropathy should be suspected in patients with nausea, vomiting, early satiety, abdominal distention, and bloating following a meal, and is secondary to delayed emptying and retention of gastric contents. The delay in gastric emptying usually is asymptomatic, although glycemic control can be affected. Postprandial hypoglycemia and delayed hyperglycemia develop when the balance between exogenous insulin administration and nutrient absorption is disrupted because of gastric stasis. Therefore, gastroparesis should be considered even in the absence of GI symptoms in a patient who suddenly develops unexplainable poor glycemic control after having had satisfactory control….


Primary treatment is focused on optimizing glucose control with insulin: secondary treatment involves dietary modifications in the form of a low-fat, low-residue diet. When patients remain symptomatic despite these measures, treatment with the following prokinetic agents is recommended:

  • Erythromycin lactobionate 1.5 to 3.0 mg/kg body weight intravenously every 6 to 8 hours (acute treatment, effective in eliminating residue from stomach); common side effects are nausea and vomiting.
  • Oral treatment with cisapride (only obtained by special request because of cardiac side effects), 10 to 20 mg before meals and at bedtime (enhances gastric emptying through serotoninergic mechanisms, effective in acute conditions); minimal side effects (abdominal cramping, frequent bowel movements); long-term use may cause hyper prolactinemia, galactorrhea, menstrual irregularities.
  • Oral metoclopramide HCl is generally used with caution because of adverse reactions (nervousness, anxiety, dystonic effects, and the potential for irreversible tardive dyskinesia).
  • Oral treatment with domperidone, a peripheral dopamine antagonist (FDA approval pending),10 to 20 mg 3 to 4 times daily (accelerates gastric emptying); minimal side effects (abdominal cramping, frequent bowel movements) and rare adverse reactions (hyperprolactinemia, galactorrhea).

Diabetic Diarrhea

Intermittent diarrhea may alternate with constipation and can be difficult to treat. Diabetic diarrhea is a diagnosis of exclusion. High-fiber intake can be helpful, along with diphenoxylate (Lomotil), loperamide (Imodium), or clonidine. Small-intestine stasis contributes to bacterial overgrowth, causing diarrhea. Treatment with one of the following antibiotics for 10 to 14 days is recommended:

  • Doxycycline hyclate, 100 mg every 12 hours
  • Amoxicillin trihydrate, 250 mg every 6 hours
  • Metronidazole, 250 mg every 6 hours
  • Ciprofloxacin HCl, 250 mg every 12 hours.

A trial of pancreatic enzymes is also recommended to rule out exocrine pancreatic insufficiency. In many instances, tincture of opium is the only medication that can help the patient live a nearly normal daily life.

Neurogenic Bladder

Frequent small voidings and incontinence that may progress to urinary retention characterize this neuropathy. Confirmation of this diagnosis requires demonstration of cystometric abnormalities and large residual urine volume. Most medical treatment is inadequate, although scheduling frequent voidings every 3 to 4 hours combined with bethanechol 10 to 50 mg 3 to 4 times daily supplemented by small doses of phenoxybenzamine may be helpful. Surgical intervention may be necessary if patients do not respond to pharmacologic therapy because chronic urinary retention can lead to UTI.

Impaired Cardiovascular Reflexes

Orthostatic hypotension and fixed tachycardia are the most disturbing and disabling autonomic symptoms. Typical treatment of orthostatic hypotension includes elevating the head of the bed, compression stockings for lower limbs and torso, supplementary salt intake, and the use of fludrocortisone (0.05 mg initially with gradual increases of 0.1 mg up to 0.5 to 1 mg). This pharmacologic therapy should be used cautiously in patients with cardiac disease because it causes sodium and water retention and may precipitate CHF.

Sexual Dysfunction

Erectile dysfunction, or impotence, is defined as the consistent inability of a man to attain or keep an erection for satisfactory sexual intercourse. It is a couples’ disorder, as both patient and partner suffer. Diabetic impotence is usually caused by circulatory and nervous system abnormalities and is a very common complaint in the male diabetic population. The classic clinical picture includes a patient with normal sexual desire but the inability to physically act on that desire. If a patient says that he has morning erections, he can masturbate without problems, or his libido is abnormally low, look for other causes of impotence such as psychological problems or a low androgen state. Orgasm and ejaculation are usually normal. Even if the patient does not have any psychological problems that could cause the impotence, he may develop a secondary psychological fear of failure that could complicate the clinical picture. A woman may experience lack of lubrication and painful intercourse.

The diagnosis can be made in most cases by a good sexual, psychosocial, and medical history, a physical examination, and laboratory tests. A testosterone level should be drawn to rule out a low androgen state, which is rarely a cause for impotence.

Hyperprolactinemia is also an uncommon cause of impotence. Hemochromatosis is a condition that is underdiagnosed and is associated with impotence and glucose intolerance. Serum iron stores, including ferritin levels, are abnormally high in this disorder. If the patient has femoral bruits and/or peripheral occlusive disease, a vascular workup may help identify the cause of impotence.

It is important to be sure the patient is not taking any medications that can cause impotence such as β-blockers and thiazide diuretics. ACE inhibitors, ARBs, CCBs, and α-blockers do not generally cause impotence.

Despite the prevalence of this disorder, nearly all patients can be successfully treated with either nonsurgical or surgical means. Yohimbine HCl, a 2-adrenergic blocking agent, has been widely used as a nonhormonal medication for the treatment of impotence. However, there has been a consistent lack of data to show that it is more effective than placebo.

Testosterone given by injection or via a scrotal or skin patch is only indicated when the serum testosterone levels are low on several occasions. If there might be binding protein abnormalities, a free testosterone level is indicated. As mentioned above, a low testosterone state is rarely a cause of impotence.

Until the late 1990s, there were no truly effective oral medications for erectile dysfunction (ED). Since then, the convenience and outcomes of the treatment of ED have improved considerably as a result of the availability of the class of drugs called phosphodiesterase-type 5 (PDE-5) inhibitors, which include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). All improve erectile function in the same basic way, by inactivating cyclic GMP thereby resulting in an increase in nitric oxide levels leading to relaxation of the vessels that supply blood to the erectile tissue in the penis. The PDE-5 inhibitors do not automatically trigger erections; sexual stimulation also is needed to start the process.

Many clinical trials have shown sildenafil, vardenafil, and tadalafil improve erectile function regardless of the underlying cause or causes including diabetes. Although all of these PDE-5 inhibitors increase the number and quality of erections and sexual experiences in men with diabetes, they have slightly different chemical structures that affect how quickly they work and how quickly they wear off (Table 15.10). Which drug may be best for an individual patient is not known since there have been no studies that compared these medications.

TABLE 15.10 — Dosing of Phosphodiesterase-5 Inhibitors


The side effects of the PDE-5 inhibitors include headaches, lightheadedness, dizziness, flushing, distorted vision, dyspepsia, syncope, and MI. Men at highest risk for syncope are those taking nitrates. They may also have adverse effects in individuals with hypertrophic cardiomyopathy because of a decrease in preload and afterload, which can increase the outflow obstruction, culminating in an unstable hemodynamic state. In 1999, the American College of Cardiology and the AHA published recommendations for the use of sildenafil, which would also apply to vardenafil and tadalafil. The document reiterates caution with respect to the use of sildenafil in the following situations:

  • Patients with active coronary ischemia who are not taking nitrates
  • CHF and borderline blood pressure or low volume status
  • Complicated, multidrug, antihypertensive regimen
  • Patients taking drugs that prolong the half-life by blocking enzyme CYP3A4 (e.g., erythromycin, cimetidine).

Vacuum constrictor devices are a viable therapeutic option for diabetic patients with impotence. No surgery or injections are required, patient acceptance is excellent, and there are few side effects. The majority of these external penile devices have a vacuum chamber that goes over the penis, a vacuum pump that creates negative pressure within the chamber allowing for engorgement of the penis with blood, and a constrictor band that is placed over the base of the penis when tumescence is achieved. Side effects are minor and include ecchymoses, hematomas, and pain. These devices are effective in men with both total and partial impotence. Many patients discover that they do not need the device after a brief period of time, which indicates that a fear of failure or other psychological problems were the initial cause of impotence.

Intracavernosal injection of vasoactive agents such as papaverine or prostaglandins can be self administered and work by relaxing corporal smooth muscle. Intracavernosal injections will work best in patients with diabetic impotence whose arterial inflow and corporal veno-occlusion mechanism are normal. Side effects include the formation of painless fibrotic nodules within the corpora cavernosa and priapism. Titration guidelines should be followed when initiating therapy. Despite the route of administration, patient acceptance is also good. The Medical Urethral System for Erection (MUSE) is also available.

Penile prostheses represent an excellent surgical option for the treatment of impotence. The options range from simple malleable or semirigid prostheses to inflatable devices that use hydraulic principles to inflate and deflate the penis when desired. Surgical complications are very low, especially when the patient’s glycemic control has been acceptable prior to surgery. With the availability of oral medications, intracavernosal injections, and vacuum devices, surgery is chosen less often.


Diabetic Foot Disorders

More than half of all nontraumatic amputations in the United States occur in individuals with diabetes, and the majority of these could have been prevented with proper foot care. Efforts aimed at prevention, early detection, and treatment of diabetic foot disorders can have a significant impact on the incidence of these problems.

Detection and Treatment

The physician and patient must diligently examine the patient’s feet on a regular basis for signs of redness or trauma, especially if neuropathy is present. Lack of pain, position, and vibratory sensations caused by neuropathy, associated deformities, and vascular ischemia can facilitate the development of foot lesions. Foot pressure that is abnormally distributed predisposes a neuropathic patient to pressure ischemia and skin breakdown. Autonomic neuropathy causes decreased sweating and dry skin that can result in cracked, thickened skin that is susceptible to infection and ulceration.

Pressure perception can be assessed using the Semmes Weinstein (SW) monofilaments, which are available in three thicknesses: 1-g fiber (SW 4.17 rating), 10-g fiber (SW 5.07 rating), and 75-g fiber (SW 6.10 rating). The following evaluation procedure has been recommended:

Place the monofilament against the skin and apply pressure to different areas of the bottom of the foot until the filament buckles. The patient should be able to feel the monofilament when it buckles and identify the location being tested. The 5.07-thickness monofilament, which is equivalent to 10-g of linear pressure, detects the presence or absence of protective sensation and is useful for identifying a foot at risk for ulceration and in need of special care.

Daily inspection of feet can help detect early skin lesions, and proper footwear can minimize the development of foot problems. Patients should be taught to cut toenails straight across, not trim calluses themselves, regularly wash their feet with warm water and mild soap, and avoid going barefoot or wearing constricting shoes. Minor wounds that are not infected can be treated with mild antiseptic solution, daily dressing changes, and foot rest.

Podiatrists should be consulted for assistance with more serious foot problems and for regular nail and callus care in high-risk individuals. If an ulcer develops, the skin must be debrided and the pressure alleviated; infections should be treated promptly with medications appropriate for the offending organism. Healing is facilitated by bed rest with foot elevation and the use of an orthopedic walking cast to relieve pressure but allow mobility. IV antibiotics, surgical debridement, distal arterial revascularization, and local foot-sparing surgery may help prevent amputation in cases of seriously infected foot ulcers.

Suggested Reading

Abuaisha BB, Costanzi JB, Boulton AJ. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. Diabetes Res Clin Prac. 1998;39:115-121.

American Diabetes Association. Preventive foot care in people with diabetes. Diabetes Care. 2004;27(suppl 1):S63-S64.

American Diabetes Association. Diabetes 2002 Vital Statistics. Alexandria,VA: American Diabetes Association; 2002. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998;280:1831-1836.

Bays HF, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patient with Type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008;168:1975-1983.

Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with Type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.

Cheitlin MD, Hutter AM, Brindis RG, et al. Use of sildenafil (Viagra) in patients with cardiovascular disease. Technology and Practice Executive Committee. Circulation. 1999;99:168-177.

Cohen KL, Harris S. Ef_ cacy and safety of nonsteroidal anti-inflammatory drugs in the therapy of diabetic neuropathy. Arch Intern Med.1987;147:1442-1444.

Davidson MB. Diabetes Mellitus: Diagnosis and Treatment. 3rd ed. New York, NY: Churchill Livingstone; 1991.Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.

Diabetic Retinopathy Study Research Group. Indications for photocoagulation treatment of diabetic retinopathy, DRS report no. 14.Int Ophthalmol Clin. 1987;27:239-253.


© Copyright 2010. Steven V. Edelman, MD, Robert R. Henry, MD, Professional Communications, Inc. All rights reserved.