Diabetes mellitus (DM), both type 1 and type 2, affects many organ systems, particularly the heart, eyes, kidneys, and the peripheral and autonomic nervous systems. Also, macrosomia and birth complications occur more often in infants born to women with inadequately controlled diabetes mellitus.
Prevention of macrovascular complications depends on control of the major risk factors for cardiac disease, such as smoking, blood pressure, and blood lipid concentrations; blood glucose control has been less effective in controlled trials. For prevention of microvascular damage, glycemic control is essential, and control of blood pressure and other vascular parameters is also important.
1. Cardiac Complications1
Cardiovascular disease (CVD) is the leading cause of mortality in individuals with diabetes. Morbidity due to CVD is also common. Control of cardiac risk factors is therefore critical. These include smoking, hypertension, and hyperlipidemia (see chapters on CHD, hypertension, and hyperlipidemia ).
Patients with diabetes may have atypical presentations for CVD. Screening with electrocardiogram or cardiac stress tests may be appropriate in some patients.
Blood pressure control is particularly important for individuals with diabetes. The goal blood pressure should be less than 130/80 mmHg, and further lowering may be beneficial (see Hypertension ).
The goals for blood lipid concentrations are also somewhat different for patients with diabetes. LDL should be less than 100 mg/dl, and in certain patients (especially those with known CVD), the goal may be less than 70 mg/dl. In known cases of CVD, triglycerides should be less than 150, and HDL greater than 40 mg/dl. HDL greater than 50 mg/dl may be an appropriate goal for women (see Hyperlipidemia ).
Dietary and behavioral modifications, including smoking cessation, regular exercise, and loss of excess weight, are critical for the prevention and management of cardiac complications in diabetes patients.
When further therapy is needed, specific medicines are usually helpful.
Aspirin therapy (75-325 mg/day) is recommended for most persons older than 30 years of age, particularly in the presence of additional cardiovascular risk factors or documented cardiovascular disease. Potential side effects, including bleeding, must be considered. Because of the risk of Reye's syndrome, aspirin therapy should not be instituted in patients under 21 years.
Hypertension in diabetes should be treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Further drugs to lower blood pressure may be required. These include diuretics, beta blockers, and calcium channel blockers (see Hypertension).
Statins and fibrates are likely to be effective in reducing cardiovascular events, and other lipid-lowering therapies may also be tried in combination (see Hyperlipidemia ).
To reduce the risk of cardiac complications, the appropriate dietary changes are those that improve plasma lipid concentrations, reduce blood pressure, and control glycemia. These steps are discussed in detail in the chapters on coronary heart disease, hyperlipidemia, hypertension, and diabetes.
A substantial body of evidence suggests that a combination of a vegetarian diet, regular exercise, smoking cessation, and stress management yields greater improvements in indices of cardiovascular disease, compared with other regimens.2,3 The Multicenter Lifestyle Demonstration Project, which included 440 patients with coronary artery disease, of whom 91 also had diabetes, showed that such a regimen is effective in individuals with diabetes, just as it is for those without diabetes.4 In a randomized, controlled trial of individuals with type 2 diabetes, a low-fat, vegan diet reduced LDL cholesterol concentrations by 21% and reduced triglycerides by 16% among participants whose lipid-lowering medications were held constant.5 The type of carbohydrate that predominates in the therapeutic diet may be clinically important. Diets high in refined carbohydrate may increase triglyceride concentrations for some individuals, but high-carbohydrate diets that are drawn from high-fiber and low-glycemic index foods appear to have the opposite result.6
A randomized controlled clinical trial of alpha-lipoic acid, administered at 800 mg/d for 4 months, showed improvements in symptoms of cardiac autonomic neuropathy.7 Further study with a larger number of individuals is required before this treatment can be recommended.
Glaucoma and Cataracts
In diabetes, pathologic changes in the retinal vasculature pose a major long-term threat to vision. In nonproliferative diabetic retinopathy, microaneurysms, small "dot and blot" hemorrhages, hard exudates (lipid material that can be toxic to the retina), and retinal infarcts known as "cotton wool spots" appear. These changes tend to concentrate in the macula, where they can blur and distort central vision.
In proliferative retinopathy (neovascularization), fragile, abnormal vessels grow into the vitreous, presumably in response to ischemia. Vitreous hemorrhage causes symptoms ranging from "floaters" to complete visual obscuration. Ultimately, tractional retinal detachment can result. Retinopathy is not painful. As a result, the condition can progress without its being detected by the patient.
Good blood glucose control, as indicated by a low hemoglobin A1c, can reduce the risk of ophthalmic involvement and slow its progression.8-12 Similarly, blood pressure control is important, as poorly controlled hypertension increases the severity of retinopathy.13-15
- Poor blood glucose control.
- Duration of diabetes.
Retinopathy can be diagnosed by ophthalmoscopy with dilated pupils.
Use of a fundus lens at the slit lamp allows a stereoscopic view and facilitates diagnosis of macular edema.
In fluorescein angiography, an intravenous injection of fluorescein followed by serial photography of the fundus reveals leakage from microaneurysms, nonperfusion, and other useful information to guide therapy.
For proliferative retinopathy, where vitreous hemorrhage appears likely, panretinal laser photocoagulation often stabilizes neovascularization or even causes it to regress.
When diabetic retinopathy causes clinically significant macular edema (defined by severity of leakage and proximity to the central macula), photocoagulation can slow progression.16 Individual microaneurysms can be obliterated, or a broader grid photocoagulated, if the leakage pattern is diffuse.
Nutritional interventions that improve control of blood glucose, blood pressure, and lipid concentrations may help prevent or slow ophthalmic complications.
Most individuals with diabetes are known to be insulin resistant, and evidence indicates that 85% of persons with type 2 diabetes also have the metabolic syndrome.17 Both of these conditions are associated with elevated intraocular pressure, a well-known risk factor for glaucoma.18 Control of high blood pressure (a component of the metabolic syndrome) is also important in the care of glaucoma (see Glaucoma ). Dietary treatments that address these underlying conditions have not yet been found to prevent or treat glaucoma.
Individuals with diabetes are at increased risk for cataract. However, no controlled clinical trials using nutrition therapies indicate that diet changes reduce this risk among individuals with diabetes. In the general population, a number of dietary factors are associated with lower cataract risk, including maintenance of ideal weight and normal lipid levels; high intake of antioxidant-containing foods; avoidance of alcohol; and avoidance of sources of galactose (ie, dairy products) (see Cataract ).
Evidence indicates that control of blood glucose,11,12 blood pressure,19 and blood cholesterol20 reduces the onset and progression of diabetic retinopathy.A21,22 A specific diet therapy suitable for prevention of retinopathy has not yet been established. However, evidence from the Diabetes Complications and Control Trial (DCCT) associated diets high in fat and low in fiber with progression of retinopathy,23 suggesting that low-fat, high-fiber diets diet may have promise for reducing retinopathy risk.
Diabetic nephropathy involves pathologic changes to the kidney vasculature. If uncontrolled, the disease progresses from microalbuminuria to macroalbuminuria and an elevated plasma creatinine concentration, and eventually to end-stage disease requiring dialysis or transplant. Pathogenesis involves hypertension, ischemia, hyperglycemia, and advanced glycosylation end products. Persistently elevated blood glucose, blood pressure, and cholesterol and triglyceride concentrations are associated with microalbuminuria.24
All individuals with diabetes are at risk for nephropathy. Pima Indians with type 2 diabetes have a particularly high susceptibility to nephropathy, with a 50% incidence after 20 years. However, Pimas living in the U.S. are at much higher risk, compared with Pimas in Mexico, suggesting that the risk among Pimas may be, in part, mediated by diet and lifestyle, rather than genetic factors. African Americans with type 2 DM appear to have more than 4 times the risk of end-stage renal disease, compared with Caucasians.25 This may also be true for Native Americans and Mexican Americans.26
Risk factors include:
- Family history of diabetes nephropathy.
- Poor blood glucose control.
- Concomitant hypertension.
- Elevated glomerular filtration rate.
- Dietary factors (see Nutritional Considerations below).
Other possible risk factors include obesity, increasing age, duration of DM, and smoking.
Microalbuminuria, defined as a persistent loss of albumin in the urine of 30 to 299 mg/day, is the first indication of nephropathy. Macroalbuminuria is diagnosed when urinary albumin losses are ≥300 mg/day.
A random urine specimen with an albumin concentration of greater than 30 mg/L suggests microalbuminuria. False-negative or false-positive results may occur due to urine volume at time of collection.
A urine albumin/creatinine ratio with a value of 30 μg/mg or greater also suggests microalbuminuria.
Transient microalbuminuria may occur with hyperglycemia, exercise, heart failure, and febrile illness.
When screening suggests microalbuminuria, a repeat specimen (albumin/creatinine ratio) should be obtained after waiting at least 1 to 2 weeks. A standard urine test strip can usually detect macroalbuminuria (1+ or greater). Albumin-specific test strips can detect microalbuminuria. However, false-negatives and false-positives are possible when using test strips. Twenty-four hour urine samples are not required to make these diagnoses.
Treatment recommendations for nephropathy are similar in type 1 and type 2 diabetes.
Glycemic control is essential for preventing further kidney damage.
Treatment with angiotensin-converting enzyme (ACE) inhibitors or/and angiotensin receptor blockers (ARBs) helps prevent the progression of microalbuminuria to more severe renal disease. This approach is especially important if hypertension is present, and target blood pressure to reduce vascular complications is less than 130/80 mmHg. Diltiazem, verapamil, and low-dose diuretics (because hypertension in diabetes is often volume dependent) may also be indicated.
Control of plasma cholesterol and triglyceride concentrations is important (see Hyperlipidemia for details on optimizing LDL, HDL, and triglycerides).
Weight loss is helpful, perhaps because of its beneficial effects on glucose, blood pressure, and lipid control.27
Reducing saturated fat, cholesterol, and animal protein intake may reduce the risk for or progression of nephropathy. Elevated cholesterol is a risk factor for nephropathy28 and end-stage renal disease.29 Cholesterol-lowering treatment was found to retard the progression of diabetic nephropathy.30
Restriction of animal protein reduces the progression of diabetic nephropathy.31 Excessive intake of total protein and animal (not vegetable) protein has been shown to increase urinary albumin excretion.32 In short-term studies, proteinuria has been reduced through the use of vegetarian diets33 and diets deriving protein primarily from soy and other plant sources.34 These diets also facilitate blood pressure control,3 which further helps reduce diabetic nephropathy progression.35
Dietary sodium restriction is indicated for a number of reasons, including prevention or treatment of microalbuminuria. It is also important because sodium excess may offset both the antihypertensive and antiproteinuric effects of renin-angiotensin system blocking drugs.36
Neuropathy is a particularly common diabetes complication, affecting approximately half of all diabetes patients. Distal symmetric polyneuropathy is the most common presentation. However, neuropathy can also involve the autonomic nervous system and individual nerves.
The disease may present with sensory loss, but also with paresthesia and dysesthesia in the affected areas. Pathogenesis may occur due to ischemia and metabolic factors, including advanced glycosylation end products. Progression is likely. If severe, neuropathy may lead to joint deformities and infections that ultimately require amputation.
- Poor blood glucose control. Good glycemic control helps prevent neuropathy, and improvement of previously poor glycemic control can improve neuropathic symptoms.10
- Duration of diabetes.
The presence of distal symmetric polyneuropathy can be assessed with simple clinical tests. Altered sensation, whether vibration (128 Hz tuning fork), pain (pin-prick), temperature, or pressure (10-g monofilament at dorsal aspect of great toe), or absence of ankle reflexes suggests neuropathy. The use of more than one test increases diagnostic accuracy.1 Electrophysiologic studies such as nerve conduction tests can confirm the diagnosis.
The presence of autonomic neuropathy can be assessed by history and physical examination. Constipation, incontinence, erectile dysfunction, tachycardia, pupillary dysfunction, and orthostatic hypotension, among other abnormalities, suggest autonomic neuropathy.
Diabetes neuropathy is best addressed through primary prevention, which requires tight glycemic control. In cases of pre-existing neuropathy, symptoms may improve with diet and lifestyle changes, as noted below.
In addition to optimized glycemic control, foot care is essential. Properly fitted shoes, foot hygiene, daily foot inspection (special mirrors can help patients who have mobility problems), regular nail care (without cutting nails too short), and immediate consultation with a health care provider whenever an abnormality occurs are all important.
Medications also may help alleviate pain symptoms of diabetes neuropathy. Examples include:
- Tricyclic antidepressants.
- Capsaicin cream.
- Anticonvulsants, such as carbamazepine and gabapentin. Phenytoin has shown inconsistent results, and other anticonvulsants are under study. Mexiletine may be substituted for carbamazepine, in consultation with a cardiologist, if pain persists. Pregabalin is structurally similar to gabapentin, but has a different mechanism of action.
- Duloxetine, a dual serotonin and norepinephrine reuptake inhibitor.
Medications may treat autonomic symptoms, such as erectile dysfunction, gastric abnormalities, and incontinence. These treatments usually improve quality of life, but do not alter the disease course.
A combination of a vegetarian diet and exercise may have particular value in treating neuropathy. In a study of 21 individuals with painful neuropathy, symptoms completely disappeared in 17 and improved in the remainder using a vegan diet along with regular walking.37 Evidence suggests that in addition to the effect of vegetarian diets on glycemic control, their effect on body weight, blood pressure, lipids, and blood rheology may be relevant to neuropathy.38,39 Future clinical trials are needed to determine the value of dietary modifications for this condition.
In addition to the benefits of a diet and exercise regimen, some nutritional supplements have shown potential benefit. Alpha-lipoic acid, in both intravenous and oral forms (≥600 mg/day), appears to be safe and effective for improving symptoms of diabetic neuropathy in clinical trials.40,41 Long-term safety and efficacy have yet to be established. Although an antioxidant action is presumed, alpha-lipoic acid also improves microcirculation.42 Other supplements under investigation for neuropathy treatment include gammalinolenic acid,43,44 carnitine,45, 46 and magnesium.47
Complications for the Newborn
Because of the insulin antagonist effect of pregnancy, some women develop DM only during pregnancy (gestational diabetes). Although gestational diabetes is not associated with an increase in congenital anomalies, it can cause other difficulties, such as macrosomia, birth trauma, and an increased risk of cesarean section.
Avoidance of complications requires good glycemic control before most women recognize that they are pregnant. Women with diabetes can be counseled to plan their pregnancies, so that good control can be in place early.
Control of blood glucose has been shown to prevent macrosomia. Complications of delivery, including shoulder dystocia, increase with newborns that are more than 4000 grams (macrosomic). Elevated glucose contributes to macrosomia, and control of blood sugar (eg, with insulin) reduces this risk.48, 49
What to Tell the Family
The best way to prevent diabetes complications is through aggressive control of blood glucose and cardiovascular risk factors. Diet plays an important role, along with exercise and appropriate medications. Encouraging the entire family to adopt a healthy diet is important, not only to support dietary adherence by the patient, but also to reduce the family's risk of disease.
All diabetes patients should be screened yearly for retinopathy by an ophthalmologist and have lab work done to monitor for nephropathy. Neuropathy is most likely to be discovered by the patient, but the family can help monitor for blisters or calluses. Special shoes may be needed to prevent infections.
It is important for the family and patient to understand that because diabetes complications can greatly reduce quality of life, aggressive prevention and/or treatment is imperative.
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