to delay or possibly halt progression.
The most relevant diagnostic sign is microproteinuria. Microalbuminuria screening should be started not later than five years after diagnosis of type 1 diabetes, and at the time of diagnosis of type 2 diabetes. For correct diagnosis and follow-up monitoring, quantitative determination of albumin in urine collected over precisely measured time periods is essential. An albumin excretion rate (AER) below 30 mg per 24 hours (20 μg/min) is considered normal, whereas an AER above 300 mg per24 hours (200 μg/min) is considered to define macroalbuminuria or proteinuria. In between these two extremes is the range of microalbuminuria. Alternatively, the urinary albumin/creatine ratio may be determined [189].
Prevention and treatment of diabetic nephropathy is based on achieving near-normal metabolic control [127,129–131,199–202], lowering elevated blood pressure to values below 130/80 mmHg [157,158,191], a normal protein intake of 0.8-1.2 g/kg body weight [203,204], cessation of smoking (if applicable), and diagnosis and treatment of nondiabetic renal or urinary tract disease.
In normotensive diabetic subjects ACE inhibitors do not reliably prevent the development of microalbuminuria [205]. In normotensive patients with microalbuminuria, captopril and calcium channel blockers [206–212] retard the progression of nephropathy. In hypertensive subjects both the ACE inhibitor captopril and the β-adrenergic blocker atenolol retard the development of microalbuminuria [158,206]. In hypertensive diabetic subjects with micro- or macroalbuminuria, lowering blood pressure with ACE inhibitors, β-adrenergic blockers, or calcium channel blockers retards the progression of albumin excretion [213–221]. While the UK Prospective Diabetes Study (UKPDS) suggested that blood pressure reduction itself may be more important for nephroprotection than the type of drug used for treatment, recent secondary prevention studies in type 2 diabetic subjects suggest that inhibition of the renin - angiotensin system may be more advantageous than other antihyperintensive therapy. In studies with ACE inhibitors [222] and with angiotensin receptor blockers [223–225] the nephroprotective effect was beyond that attributable to blood pressure control.
Cardiovascular risk is increased at any stage of diabetic nephropathy, and the majority of patients with such nephropathy will die not of uremia but of macrovascular complications [183,184,188,226]. Prevention of these complications is mandatory, and risk factors for macroangiopathy other than hypertension should also be treated.
Diabetic nephropathy is accompanied by lipid disorders which are believed to contribute essentially to the high cardiovascular risk [227]. Treatment of dyslipoproteinemia is mandatory, as are “stop smoking” programs for smokers.
Platelet aggregation inhibition with aspirin is recommended in diabetic patients with albuminuria [228]. Radiopaque media should only be used after careful hydration of the patient [229].
Patients with endstage renal disease will need renal replacement therapy. Chronic hemodialysis, peritoneal dialysis (intraperitoneal, continual ambulatory), and renal transplantation in combination with pancreas transplantation [230] are presently the methods of choice. The prognosis of patients who have undergone transplantation has recently been improved but still is not as good as in non-diabetic subjects [176,187,230].
Almost 100% of patients with endstage renal disease also have diabetic retinopathy and/or diabetic neuropathy. Monitoring and treatment of these complications is equally important.
Macroangiopathy
The term “macroangiopathy” was introduced by Lundbaek [231] to draw attention to the fact that large-vessel disease in diabetes is not just a matter of atherosclerosis occurring in a diabetic subject, but is a facet of diabetic angiopathy as important as microangiopathy. The major clinical complications of macroangiopathy are coronary artery disease, stroke, and amputation. Only coronary artery disease will be discussed in more detail in this chapter.
Epidemiology
Due to the insidious course of macroangiopathy and the difficulties of early diagnosis, reliable population-based data on its incidence and prevalence are lacking. Some epidemiological data on the clinical manifestations are available [232]. The figures for their incidence and prevalence in diabetes depend on their occurrence in the general population to which they belong and differ considerably between countries [233]. However, clinical, epidemiological [154,234–236], and autopsy studies [237,238] and cause-of-death statistics [29,239] agree that the figures are higher in people with type 1 diabetes/IDDM and type 2 diabetes/ NIDDM than in the general population. After 30 years of IDDM, cardiovascular disease accounts for two-thirds of all deaths [21]. Macroangiopathy develops earlier in life and occurs almost independently of gender [154,240].
