THE CHRONIC COMPLICATIONS OF DIABETES The seriousness of diabetes complications cannot be overstated. Prolonged high blood sugar levels can lead to both microvascular and macrovascular complications. Microvascular complications may be "warning signals" for impending macrovascular complications. MICROVASCULAR COMPLICATIONS Retinopathy There are two types of diabetic retinopathy that can develop without warning: proliferative diabetic retinopathy (PDR) and macular edema. In some cases, patients may be unaware of retinopathy until they suffer sudden significant vision loss. Upon diagnosis of NIDDM, the patient should be referred to an ophthalmologist. If retinopathy is discovered before symptoms occur, visual loss can be slowed, if not stopped completely, by laser photocoagulation. Optimal glycemic and blood pressure control in patients with diabetes may also delay the onset and progression of retinopathy. It is recommended that people with NIDDM or IDDM over the age of 40 see their eye doctor annually. People diagnosed with IDDM before the age of 40 should visit their opthalmologist annually after having diabetes for five years. Almost all people with diabetes will experience some form of retinopathy; however, only 40 to 50 percent will progress to PDR. The prevalence of retinopathy increases with age, and more than 97 percent of all people with diabetes who suffer from total blindness caused by retinopathy are over the age of 50. When retinopathy is present family physicians detect 25 percent, internists detect 50 percent and ophthalmologists detect 75 percent of retinopathy. Colour stereo photographs and fluorescent angiograms are the gold standard. Intensive insulin and blood glucose therapy of patients with IDDM delays the onset and slows the progression of clinically important retinopathy including vision-threatening lesions, as well as nephropathy and neuropathy by a range of 35 to more than 70 percent. Neuropathy and Foot Problems Neuropathy is common in patients with diabetes and, in NIDDM, may be detected soon after diagnosis. Depending upon which part of the nervous system is affected, neuropathy can be disabling. Severe neuropathy is almost always associated with prolonged blood glucose elevation and can be prevented. At initial visit, physicians should question patients regarding symptoms related to the sensory (numbness, anesthesia), motor (weakness) and automatic (gastrointestinal and bladder symtoms, sexual dysfunction) nervous systems. Most neuropathy symptoms start in the feet and usually consist of "pins and needles" or numbness. These major warning signs means particular attention should be paid to preventative foot care. People with diabetes are particularly prone to foot problems that can result in disability, prolonged hospitalization and even mortality. In patients with neuropathy (which diminishes sensation leading to unawareness of injury or pain) or macrovascular damage, a minor bruise or cut, large calluses or improper toenail cutting can lead to skin ulcers, infections, gangrene or even amputation. Calluses should be treated with pumice stone after bathing and advise patients not to "shave" calluses. Toe nails should be cut straight across. Feet should not be soaked in salty solutions. Patients with long-term diabetes should be tested for neuropathy. A diabetes examination should pay special attention to the feet. The importance of proper footwear and never walking barefoot should be stressed. Each foot should be examined for general hygiene, the condition of the skin and the toenails, calluses or bunions and vascular, joint and neurologic integrity. Nephropathy and Microalbuminuria Diabetic nephropathy is a major cause of the excess morbidity and mortality associated with diabetes, especially in those with IDDM. Microalbuminuria predicts morbidity and mortality from renal and cardiovascular disease. Dipstick tests at initial examination will determine whether the urine contains gross proteinuria. If it does not, a dipstick for microalbuminuria and an overnight or 24-hour sample for microalbuminuria should be performed. Micoralbuminuria testing should also be done with each annual physical in NIDDM and after five years of IDDM. If a test for microalbuminuria is positive (>30 mg/24 hours), blood pressure must be kept below 135/85 by the use of antihypertensive agents. There is good evidence that, in the presence of microalbuminuria without hypertension, ACE inhibitors reduce microalbuminuria and the progression to renal insufficiency. Other preferred medications include calcium channel blockers and alpha-blockers (see Drugs and Medication). Any lowering of the HgbA1c will reduce the degree of microalbuminuria, as well as other complications. Studies show that intensive insulin therapy reduces the risk of microalbuminuria in IDDM by 39 percent. The ability of intensive therapy to reduce the development of nephropathy suggests its preventability. MACROVASCULAR COMPLICATIONS Cardiac Events More than 70 percent of NIDDM patients will die of cardiovascular , cerebrovascular or peripheral vascular disease. Furthermore, cardiac ailments account for more than 75 percent of all hospitalizations for diabetic complications. Women with diabetes have a five times greater risk of developing cardiovascular disease than women without diabetes. Men with diabetes have a two to three times greater risk of developing cardiac problems than those without diabetes. Women with diabetes have five times the risk for claudication as healthy women, while men have a two to three times greater risk than their healthy counterparts. The risk of suffering strokes also increases two-to-three-fold in people who have diabetes. Hypertension Hypertension often accompanies diabetes and is linked to obesity, high cholesterol levels, elevated triglycerides, a lack of physical activity, a family history of hypertension and coronary heart disease (CHD), left ventricular hypertrophy and smoking. In addition, hypertension is more common in men than women and exacerbates such complications as retinopathy and nephropathy. Hypertension associated with diabetes increases the risk for cardiovascular, cerebrovascular and peripheral vascular disease. In Type 1 diabetes, hypertension may also suggest kidney disease. The factors contributing to hypertension are all interactive. A syndrome of insulin resistance (Syndrome X) has been described that consists of various degrees of glucose intolerance, dyslipidemia (primarily increased triglycerides and low HDL) and hypertension. Insulin resistance is the common pathogenic mechanism in this cascade, which greatly increases the risk for CHD. Studies show that the incidence of myocardial infarction in high-risk patients can be reduced by aspirin. Beta-blockers may be considered for diabetes patients who have had a myocardial infarction as these agents reduce mortality from reinfarction despite possible negative effects on serum lipids and counter-regulation during hypoglycemia. Primary Therapies for Preventing a Cardiac Event Diet (a word that really should be avoided) is the key component of first-line therapy. A healthy meal plan includes reducing fat, lowering sodium and meeting nutritional requirements in regard to calcium, potassium and other nutrients. It is essential that people with diabetes consult with a dietitian. Exercise is another component of first-line therapy. A thorough history of coronary atherosclerosis and a stress test should be done before initiating vigorous exercise. Other contributing factors, like smoking, stress and obesity, should be addressed. Self Blood Glucose Monitoring improves blood glucose control and reduces secondary hyperlipidemia. Sub-optimal blood pressure (mm Hg) is 150/90, while optimal blood pressure is <140/90. In the face of early nephropathy, 130-135/80-85 may be the optimal goal. The presence of orthostatic hypotension warrants the routine monitoring of standing blood pressure during the assessment and follow-up of patients with evidence of neuropathy. Drugs for Controlling Hypertension A variety of drugs constitute second-line therapy with the goal of normalizing blood pressure and lipid levels. ACE inhibitors have proven nephro-protective effects but do not have adverse effects on lipids. ACE inhibitors are relatively well tolerated and may reduce microalbuminuria. Despite the side effects of hyperkalemia, ACE inhibitors are becoming the drugs of choice in the treatment of hypertension in people with diabetes. Because of hyperkalemia, potassium levels in the blood must be monitored. Calcium channel blockers may be effective in the treatment of angina. As different agents differ in primary effects, the side effects directly relate to the drug's vasodilatory functions. Beta-blockers are another cheap and effective means of managing angina and hypertension. Unfortunately, beta-blockers may increase insulin resistance, can hide the symptoms of hypoglycemia and have unfavourable effects on serum lipid concentrations. For these reasons, beta-blockers are not recommended as first-line anti-hypertensive therapy. They are, however, the agents of choice for secondary (post-myocardial infarction) prevention. Unlike beta-blockers, alpha-blockers do not cause insulin resistance while improving the lipid profile. Tachycardia and first-dose hypotension may occur. Alpha-blockers are a potentially important component of treatment of hypertension. Direct vasodilators, like Minoxidil, are useful in the treatment of hypertensive emergencies. Side effects include tachycardia and fluid retention. Direct vasodilators are not recommended as first-line anti-hypertensive therapy. Potent diuretics (e.g., Furosemide) may increase hypokalemia significantly. These are recommended only for patients with congestive heart or renal failure. Adrenergic inhibitors and central alpha agonists lower blood pressure and the heart rate; however there are many side effects. Only alpha-methyldopa is used for pregnant women with diabetes and people with diabetes undergoing surgery. Other drugs, including indapamide and low-dose thiazides (12.5 mg/day) are inexpensive but should be used as adjunctive and not primary therapy. Higher dose thiazides may aggravate glucose and lipid levels. REFERRALS In general, because of the impact of diabetes and its complications, referral for Endocric assessment should be conducted if: * HbgA1c does not reach goal levels of at least < 0.080 * Hypertension is not controlled * Microalbuminuria is not reduced to normal within six months * Other complications (retinopathy, cardiovascular disease) intervene CONCLUSION There are many methods for treating or delaying the onset of diabetes complications. Although complications are a reality, they need not be inevitable. The key components for delaying or limiting the severity of complications are: a healthy diet, physical activity, regular eye examinations, foot care, urine tests, home glucose monitoring and regular (two to four times per year) HbA1c determinations. Removing factors that contribute to hypertension, like smoking and stress, also improves one's chances of avoiding severe complications. The importance of excellent metabolic control cannot be overestimated. Abstracted from the "Diabetes Care Without Compromise" booklet by Bill Clarke and Cynthia Lank, with the assistance of Keith Dawson MB and Denis Daneman MB.