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Editorial: Mortality and renal disease in type 1 diabetes mellitus--progress made, more to be done.

In this issue of the journal, Stadler et al. (1) provide prospective, 20-yr longitudinal data on mortality, renal disease, and their risk factors in a cohort of patients with type 1 diabetes mellitus. Renal disease has long been a dreaded complication for persons with type 1 diabetes, often a harbinger of rapid demise (2), and historically the leading cause of mortality (3, 4). Diabetes (all types) is the most common cause of end-stage renal disease (ESRD), accounting for approximately 40% of new cases in the United States. The estimated cost of diabetic ESRD in the United States was $15.6 billion in 1997 (5), including an estimated $1.9 billion in 2001 specifically for ESRD in type 1 diabetes (6). Of concern is the reported increase in the incidence of type 1 diabetes. Furthermore, though not a topic of the paper by Stadler et al. (1), type 2 diabetes is rapidly increasing, and renal complications may be more common in youth with type 2 than type 1 diabetes (7, 8). The Diabetes Control and Complications Trial (DCCT) has clearly shown the importance of glycemic control in reducing microvascular complications, including renal disease (9, 10). Despite significant advances in the care of type 1 diabetes since the initiation of the Lainz study (1) in 1983–1984, 13% of the 684 patients in this relatively young cohort (30 11 yr at inception with type 1 diabetes duration of 15 9 yr) died over 20 yr, with 5.6% receiving renal replacement therapy. Of note, the leading cause of death in this cohort was cardioand cerebrovascular disease (38%), followed by diabetes-associated deaths with and without renal complications (29%) accounting for over two thirds of the cohort’s deaths. These deaths, in part, should be considered preventable and should rouse clinicians and their patients to greater efforts to improve diabetic care to prevent complications and limit premature mortality. These data are of importance to the endocrine community as a reminder that kidney disease and premature death remain all too frequent among persons with type 1 diabetes. A particular strength of this paper was the inclusion of all eligible patients at the time of enrollment and the ability to use nationwide databases to completely ascertain renal replacement therapy and mortality over a 20-yr period. The authors also place their data in historical context, which is important to compare the results convincingly with those of previously published studies from the 1970s and 1980s, which have reported a much higher rate of renal disease and mortality (3, 4, 11), although comparing different cohorts must be done cautiously. More recently, data from the Steno clinic have suggested reduced nephropathy after 20 yr of type 1 diabetes duration in successive 5-yr cohorts from 31.1% (1965–1969) to 13.7% (1979–1984) (P 0.015). This positive trend coincided with more antihypertensives started, lower blood pressure and HbA1c, and less smoking in later cohorts (12). Similarly, after 30 yr of duration, a decline in successive 5-yr cohorts from 32.1% (1961–1965) to 10.8% (1966–1970) (P 0.005) (13) has been reported in the Linkoping Study. By 35 yr duration, the reported cumulative incidence of 21.3% (14) is an apparent decrease from previous estimates from the Joslin clinic (15). Population-based estimates have reported ESRD of 2.2% at 20 yr and 7.8% at 30 yr in patients diagnosed in Finland between 1965 and 1999 (16). In this Finnish population-based study, cumulative mortality was 6.8% and 15.0% at 20 and 30 yr after the diagnosis of type 1 diabetes, respectively (16). More data supporting improved outcomes over time come from the Pittsburgh Epidemiology of Diabetes Complications Study, which documents decreased mortality and renal failure, though not coronary artery disease, in each progressive cohort diagnosed in subsequent time periods from 1950–1959 to 1975–1980 (17). A limitation of the study by Stadler et al. (1) is that the analyses are based solely on the baseline data and they are unable to report on how therapeutic advances may have influenced changes in risk factor levels. For instance, glycemic control has improved significantly with home blood glucose monitoring, multiple daily injections, insulin analogs, continuous sc insulin infusion, and more recently continuous glucose monitoring. The authors’ data affirm the importance of glycemic control (although HbA1c was only available in a subset of 500 subjects) and its importance on reducing renal complications and mortality and also affirm that renal disease (both microand macroalbuminuria) predicts mortality. Unfortunately, the authors do not have data on blood-pressure-lowering medication usage—a standard of care for type 1 diabetes patients with hypertension or albuminuria—and therefore they are unable to comment on the effect of these medications for renal protection and reduction in mortality. Studies have demonstrated that angiotensin-converting enzyme/angiotensin receptor blocker treatment slows progression to diabetic nephropathy in type 1 diabetes and suggest an additional beneficial effect on cardiovascular disease (CVD)—independent of blood pressure lowering—in persons with diabetes (18, 19). Other important risk factors such as smoking and lipids and their treatment are not reported. Although type 1 patients have been reported to have relatively better lipids (20), elevated lipids remain a risk factor for macro(21) and microvascular (22) disease. Current guidelines consider type 1 diabetes as a CVD risk equivalent, and the goal for low-density lipoprotein cholesterol is 100 mg/dl, with an even lower goal of 70 mg/dl in individuals with overt CVD (23). Abbreviations: CVD, Cardiovascular disease; ESRD, end-stage renal disease.