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CMAJ
CMAJ - October 20, 1998JAMC - le 20 octobre 1998
Diabetes Supplement

1998 clinical practice guidelines for the management of diabetes in Canada

Supplement to CMAJ 1998;159 (8 Suppl)

© 1998 Canadian Medical Association


Complications

Major acute complications of diabetes are hypoglycemia and hyperglycemic crises including ketoacidosis and hyperglycemic-hyperosmolar states. A person with diabetes experiencing an acute complication may be treated in an ambulatory setting or require emergency admission to a hospital ward or an intensive care unit. Once a patient has recovered from such an episode, appropriate education by the DHC team is necessary to prevent recurrences.

Long-term complications may occur in both type 1 and type 2 diabetes. These include macrovascular complications (CAD, cerebrovascular disease, and peripheral vascular disease) and microvascular complications (retinopathy, nephropathy, neuropathy and foot problems).

Regular, systematic surveillance for these acute and long-term complications is an integral component of comprehensive diabetes care. An organized and coordinated approach should be implemented for follow-up visits.

Retinopathy

Diabetic retinopathy is the major cause of adult blindness in North America and likely the most feared of the long-term complications. Diabetes is the sole or contributing cause of blindness in about 86% of the eyes of people with type 1 diabetes, and in 33% of the eyes of people with type 2 diabetes.169 Proliferative retinopathy occurs in 23% of patients with type 1 diabetes, 14% of people with type 2 diabetes taking insulin and 3% of people with type 2 diabetes not taking insulin;170 macular edema occurs in 11%, 15% and 4% of these groups, respectively.171 Patients with diabetes are also at increased risk of developing cataracts.172 Evidence for increased risk of primary open-angle glaucoma is conflicting.173,174

Screening strategies for sight-threatening retinopathy (i.e., proliferative retinopathy or macular edema) must reflect differences in the incidence and prevalence of retinopathy in type 1 and type 2 diabetes.175,176,177,178 Development of diabetic retinopathy in children under 10 years of age with type 1 diabetes is rare regardless of the duration of diabetes.177 The prevalence rate increases sharply after 5 years duration of diabetes in postpubertal people with type 1 diabetes.177 Conversely, retinopathy may be present in 21% of people soon after clinical diagnosis of type 2 diabetes, but is vision-threatening in only about 3%.171,173–176 Important predictors of the progression of retinopathy are longer duration of diabetes, higher level of glycated hemoglobin, more severe retinopathy, higher blood pressure, higher lipid levels and, in type 1 diabetes, pregnancy.152,175–178,179,180

The "gold standard" for assessing diabetic retinopathy is 7-standard field, stereoscopic-colour fundus photography.181 Seventy-nine per cent agreement in the detection of proliferative retinopathy can be achieved by fundus examination by direct ophthalmoscopy through dilated pupils carried out by highly trained personnel (regardless of professional designation).182 Examinations by inexperienced observers or examinations through undilated pupils fail to detect proliferative retinopathy in about 50% of patients and macular edema in all cases.183,184 Contact lens fundus biomicroscopy by retinal specialists results in 81% agreement in the detection of clinically significant macular edema.185 The Early Treatment Diabetic Retinopathy Study's final scale is the best means of categorizing the severity of retinopathy and provides important prognostic information.186

In type 1 diabetes, the onset of retinopathy can be delayed or its progression slowed by intensive insulin therapy, with achievement of improved control.77 In type 2 diabetes, epidemiologic studies show that hyperglycemia is an independent risk factor for the incidence and progression of retinopathy; however, the risks and benefits of insulin therapy have not been completely established.4,187

In both types of diabetes, elevated diastolic blood pressure is a risk factor for the development of macular edema,180,188 and elevated systolic blood pressure is a risk factor for loss of vision.189 People with elevated serum cholesterol, low-density lipoprotein (LDL) cholesterol or triglyceride levels are more likely to have or develop retinal hard exudate, which can be associated with risk of loss of vision independent of the extent of macular edema.179 Retinopathy can become worse during pregnancy, independent of higher levels of glycated hemoglobin.152

Focal/grid laser treatment for clinically significant macular edema reduces loss of vision by 50%.190 Full implementation of scatter laser treatment and vitrectomy reduces legal blindness by 90% in patients with severe nonproliferative or proliferative retinopathy.191,192,193 In type 1 diabetes, early vitrectomy performed for nonclearing, severe vitreous hemorrhage provides a better chance of visual recovery than if treatment is deferred. In type 2 diabetes, early vitrectomy has no such benefit and carries a 2-fold higher overall risk of serious untoward events than if deferred for 1 year.194 In people with type 1 or type 2 diabetes, early vitrectomy for advanced active proliferative retinopathy unresponsive to laser treatment achieves significant recovery of visual acuity compared with conventional management.195

Recommendations

  1. The development and progression of retinopathy may be prevented through intensive diabetes management achieving optimal metabolic control [Grade A Level 176,77] and treatment of elevated blood pressure or lipid levels. [Grade D, Level 4179,188,189]
  2. In people with diabetes, screening for sight-threatening retinopathy should be performed by experienced professionals highly trained in direct ophthalmoscopy through dilated pupils or by retinal specialists. [Grade A, Level 1,182,183,185 Level 2184]
  3. Screening and evaluation for retinopathy should be performed annually 5 years after the onset of diabetes in postpubertal patients (age 15 years or over) with type 1 diabetes and in everyone with type 2 diabetes at the time of diagnosis. [Grade A, Level 1175] The interval for follow-up assessments should be tailored to the severity of the retinopathy. In those with type 2 diabetes who have no or minimal retinopathy, the recommended interval is 2 years and should not exceed 4 years. [Grade A, Level 1176,178]
  4. Women with type 1 diabetes should have an ophthalmic assessment before conception in a planned pregnancy and in the first trimester of pregnancy and be followed up as needed during pregnancy. [Grade A, Level 1152]
  5. Proliferative or severe nonproliferative retinopathy necessitates referral to an ophthalmologist or retinal specialist with access to surgical facilities. [Grade A, Level 1190–195]
  6. Visually disabled people should undergo low-vision evaluation and rehabilitation. [Grade D, consensus]

Nephropathy

Diabetic nephropathy is the number one cause of end-stage renal failure in Canada and the western world.196,197,198 The costs of dialysis and renal transplantation are high. In addition, people with diabetes and end-stage renal failure have high morbidity and mortality rates due to cardiovascular disease.196–198,199,200,201,202,203

The focus of treatment of diabetic nephropathy is on prevention through early screening and detection. Elevated microalbuminuria is the earliest reliable and clinically detectable sign of progressive nephropathy in both type 1 and 2 diabetes.197,204,205,206,207,208,209,210 Screening for increased microalbuminuria is necessary 5 years after the onset of diabetes for people over 15 years of age with type 1 diabetes and at the time of diagnosis for everyone with type 2 diabetes to detect progressive nephropathy at the earliest stage.211,212,213,214,215 Once nephropathy is diagnosed, intensive glucose control,76,77,216,217,218,219,220,221,222,223,224 inhibition of angiotensin-converting enzyme (ACE),225,226,227,228,229 normalization of blood pressure230,231,232,233,234,235,236,237,238,239,240,241 and elimination of all cardiovascular risk factors242,243,244 will help prevent its progression. If overt nephropathy is evident (i.e., more than 300 mg/d of albumin in urine), all those with type 1 diabetes should receive ACE inhibitors. ACE inhibitors should also be considered for those with type 2 diabetes and overt nephropathy. Data suggest that dietary reduction of protein intake may delay progression of renal failure.245 Follow-up should include monitoring of serum creatinine and potassium, a 24-h creatinine clearance test and quantitation of proteinuria at least twice a year.

Recommendations

  1. The best possible glucose control — if necessary intensive diabetes management — should be instituted in people with type 1 diabetes for the prevention of onset and delay in progression of early nephropathy. [Grade A, Level 177,224]
  2. In people with either type 1 or type 2 diabetes, screening for microalbuminuria is recommended in those with dipstick-negative or trace proteinuria. Frequency of screening is annual for people over 15 years of age with a 5-year history of type 1 diabetes and for all people after diagnosis of type 2 diabetes. [Grade D, consensus] The recommended screening method is measurement of an albumin:creatinine ratio in a random, daytime urine sample. If values are greater than 2.8 for females and 2.0 for males, the test should be repeated (and confirmed in 2 out of 3 measurements over 3 months); if uncertainty about elevation still exists, it should be confirmed with a timed urine collection to measure the rate of microalbuminuria. [Grade A, Level 1212,215]
  3. In type 1 diabetes, elevated microalbuminuria (30–299 mg albumin in 24 h or 20–200 µg/min) should be treated with an ACE inhibitor to decrease albuminuria, even in the absence of hypertension. [Grade A, Level 1225,226,229]
  4. People with type 2 diabetes and elevated microalbuminuria (30–299 mg albumin in 24 h) may benefit from ACE inhibitor therapy to decrease albuminuria. [Grade B, Level 1227,228]
  5. People with type 1 diabetes and overt nephropathy (>300 mg albumin in urine in 24 h) should be treated with an ACE inhibitor. (Blood pressure goals should be the same as for people with hypertension.) [Grade A, Level 1233]
  6. A greater than 50% decrease in creatinine clearance rate necessitates referral to a nephrologist or internist associated with a dialysis and renal transplantation centre for adequate, well-planned long-term management. [Grade D, consensus (best practice of the Canadian Society of Nephrology)]

Neuropathy

Detectable neuropathy will develop within 10 years of the onset of diabetes in 40% to 50% of people with type 1 and type 2 diabetes. Although fewer than 50% of these people are symptomatic,77,246 neuropathic pain is frequently bothersome.247,248,249 People with type 2 diabetes may have neuropathy at the time of diagnosis, whereas it is uncommon in people with type 1 diabetes within the first 5 years after onset of diabetes. Increased risk of foot ulceration, which depends on the degree of foot insensitivity,250 and amputation are serious sequelae of diabetic neuropathy. Both somatic and autonomic neuropathy may occur and may require referral to a specialist experienced in managing the affected body system.

Neuropathy is most easily detected by examining the patient for loss of ankle reflexes and perception of 128 Hz vibration in the great toe,77 or by using a 10-g Semmes–Weinstein monofilament.251 In people with significant symptoms of neuropathy, referral for additional neurologic evaluation and to other specialists (e.g., neurologist, podiatrist, chiropodist) may be helpful.

Intensive diabetes management is effective for the primary or secondary prevention of neuropathy in patients with type 1 diabetes.77,222,252 In patients with type 2 diabetes, lower glucose levels are associated with reduced frequency of neuropathy246 and intensified therapy may also be helpful.76

Tricyclic antidepressants,247–249,253 carbamazepine,254 or mexiletine255 are often effective in controlling neuropathic pain. Adverse effects of these medications, especially mexiletine, must be considered before use. The effect of topical capsaicin is less certain.256,257 Nonaddictive analgesics may be used to alleviate pain.

Recommendations

  1. Screening for peripheral neuropathy should be carried out annually to identify those at high risk of developing foot ulcers. [Grade A, Level 1250]
  2. Detection of peripheral neuropathy can be done through assessment for
    • decrease or loss of ability to sense vibration or loss of sensitivity to a 10-g monofilament at the great toe
    • absent or decreased ankle reflexes. [Grade D, Level 4251]
  3. People with type 1 diabetes should be treated for peripheral neuropathy with intensive management for primary prevention or secondary intervention. [Grade A, Level 177,222]
  4. Intensified diabetes management should be considered for people with type 2 diabetes to prevent onset and progression of neuropathy. [Grade B, Level 176]
  5. Tricyclic antidepressants and carbamazepine [Grade A, Level 1249,254] should be considered for symptomatic relief of painful peripheral neuropathy. Topical capsaicin should be considered as a nonsystemic treatment for painful neuropathy. [Grade B, Level 1257]
  6. People with clinically significant autonomic dysfunction should be appropriately assessed and referred to a specialist experienced in managing the affected body system. Because sexual dysfunction is common, specific inquiries should be made as people may be reluctant to volunteer such information. [Grade D, consensus]

Foot care

Foot problems are a major cause of morbidity and mortality in people with diabetes and contribute to increased health care costs.258,259 The sequence of events leading to lower-extremity amputation is well known: in people with neuropathy260 or peripheral vascular disease (PVD),261 minor trauma to the foot leads to skin ulceration, infection and gangrene, resulting in amputation.262,263,264,265,266 Foot complications are a major reason for admission to hospital of people with diabetes and account for approximately 20% of all admissions in the North American population.264,265,267,268 After amputation of one limb, the prognosis for the contralateral limb is poor.269,270 Of all lower-extremity amputations, 45% occur in people with diabetes; the age-adjusted rate of amputation is 11 times higher in those with diabetes than in people without diabetes.270 More recent data indicate that one-half to two-thirds of all lower-extremity amputations performed in the United States are in people with diabetes, and these account for more than 50 000 amputations.259,266,268 In the United States, the direct costs for this common complication of diabetes, including rehabilitation, are in excess of $500 million a year.267,271

Appropriate management can prevent or heal diabetic foot ulcers, thereby greatly reducing the amputation rate.263,266,267,272,273 Prevention of amputations calls for the use of various measures, including regular foot examination and evaluation of amputation risk, patient education, early detection and treatment of diabetic foot ulcers and, if necessary, vascular surgery.267,271–274 Characteristics that have been demonstrated to confer high risk of amputation include previous ulceration, increased age, PVD, neuropathy, structural deformity, renal transplantation, poor socioeconomic status and smoking.

Recommendations

  1. Foot examination in adults should be an integral component of diabetes management and decreases risk of foot ulcers and amputation. [Grade A, Level 1273,274] Foot examination should include assessment of structural abnormalities, neuropathy, vascular disease, ulcerations and evidence of infection. [Grade D, Level 4266] Foot examinations should be performed at least annually in all people with diabetes who are over 15 years of age and at more frequent intervals for those at high risk. [Grade D, consensus]
  2. Prevention of foot ulceration and amputation requires foot care education, proper footwear, avoidance of foot trauma, smoking cessation and early referral if problems occur. People at high risk of foot ulceration should receive reinforcement of foot care education. [Grade A, Level 1273,274]
  3. A person with diabetes who develops a foot ulcer requires therapy by experienced health care professionals who have expertise in diabetes foot care. Any infection must be treated aggressively. [Grade D, consensus]

Cardiovascular disease and hypertension

Cardiovascular disease is a major cause of morbidity and mortality in both type 1 and 2 diabetes; morbidity and mortality rates are 2- to 4-fold higher than in age- and sex-matched groups in the nondiabetic population.275,276,277,278,279

The risk of CAD and stroke is increased 2-fold among men with diabetes and 3- to 4-fold among women with diabetes.278,279,280,281,282 Silent ischemia and myocardial infarction are more common and the outcome of an infarction is worse than in nondiabetic people.283,284,285 In fact, after an acute myocardial infarction, men and women with diabetes are at greater risk for congestive heart failure, have a 4-fold greater risk of recurrent infarction, a 2-fold greater risk of arrhythmias and higher short- and long-term mortality rates than nondiabetic people.286,287 They also have a lower overall survival rate.286 In addition to the risk of CAD and stroke, diabetes is associated with increased risk of PVD, which contributes to the high rate of gangrene and lower-limb amputations.276,281

The benefits of reducing CAD by modifying the major risk factors for cardiovascular disease, such as hyperlipidemia, have not been clearly assessed in people with diabetes.288 Nevertheless, subgroup analyses of people with diabetes who were enrolled in both primary289 and secondary78 prevention trials of lipid-lowering drugs suggest that reduction of LDL cholesterol can significantly decrease morbid events.

As CAD may be asymptomatic in people with diabetes, aggressive treatment including the use of acetylsalicylic therapy as a primary prevention strategy should be considered in high-risk people (over the age of 30); acetylsalicylic acid may also be effective for secondary prevention.290 There is no contraindication to acetylsalicylic acid therapy, even in people with severe stages of diabetic retinopathy who are at risk for (or who have) vitreous hemorrhage.291,292

Hypertension complicates diabetes in all populations and is more frequent with advancing age.280 In type 1 diabetes, blood pressure is usually normal at presentation. Hypertension typically develops with the onset of nephropathy and is characterized by elevation of systolic and diastolic blood pressure. About half of people with type 1 diabetes with 30 or more years of diabetes have hypertension.279 People with type 2 diabetes are frequently hypertensive at the time of diagnosis, and the increase in blood pressure is generally correlated with obesity, decreased physical activity and older age. Isolated systolic hypertension is particularly common in type 2 diabetes.293,294

Because hypertension is a major contributor to the dramatically increased morbidity and mortality of both type 1 and 2 diabetes,203,279 it should be recognized and treated early and aggressively. Although treatment of hypertension with any known antihypertensive agent may improve cardiovascular disease outcomes,241,293,294 the use of low-dose diuretics and beta-blockers may be particularly effective in the elderly.295 ACE inhibitors may also decrease cardiovascular events more than calcium channel antagonists in those at high risk.296,297 ACE inhibitors have additional advantages in the presence of diabetic renal disease. (See Nephropathy section.)

Recommendations

  1. People with type 1 or 2 diabetes should be encouraged to adopt a healthy lifestyle to lower their risk of CAD: this means achieving and maintaining healthy eating habits and a desirable weight, engaging in regular physical activity and stopping smoking. [Grade D, consensus]
  2. A fasting lipid profile (total cholesterol, triglycerides, HDL cholesterol and calculated LDL cholesterol) should be carried out in adults with diabetes and repeated every 1 to 3 years as clinically indicated. [Grade D, consensus]
  3. Appropriate treatment of dyslipidemia to achieve target levels (as noted in Table 12) should be instituted for primary prevention of CAD [Grade D, consensus] and secondary prevention of CAD. [Grade C, Level 378]
  4. Hypertension in people with diabetes (i.e., blood pressure >=140/90 mmHg) should be treated to attain target blood pressure <130/85 mmHg. [Grade D, consensus]
  5. First-line drug therapies for hypertension in people with diabetes and without overt nephropathy can include (in alphabetical order): ACE inhibitors, alpha-blockade agents, angiotensin II receptor antagonists and calcium channel antagonists. The choice of antihypertensive agents should be tailored to the individual and take into account the effects of these agents on cardiovascular, metabolic and renal outcomes. [Grade D, consensus]
  6. Hypertension treatment goals for the elderly should be tailored to the individual. [Grade D, consensus] Low-dose diuretics and beta-blockers should be considered in the elderly to prevent cardiovascular disease. [Grade A, Level 1295]
  7. Low-dose acetylsalicylic therapy (81–325 mg/d) should be considered as primary prevention therapy in high-risk patients (over the age of 30 years) with diabetes and as a secondary prevention strategy in people with diabetes and large vessel disease. [Grade C, Level 3290]