[ Diabetes Type 1 ]

is there light at the end of the tunnel?

Diabetic nephropathy is the most common cause of end-stage renal disease in the U.S. During the follow up 38 patients died and 20 (11 male and 9 female) patients developed ESRD. Renal biopsy studies suggest that 25-50% of patients with Type 2 diabetes had glomerular lesions unrelated to or in addition to diabetic nephropathy. Atorvastatin therapy was associated with a modest reduction in proteinuria and glomerulosclerosis without influencing lipid levels or renal function in STNx rats. Moreover, GFR loss has been shown to occur independently of albuminuria or even in the absence of it. Further, recently, the cross-talk between AGEs and the renin-angiotensin system (RAS) has been proposed to participate in diabetic nephropathy. For those on dialysis, the mortality rate is high with an approximately 40% fatality rate within two years after initiation of dialysis5.

The proportion of type 2 diabetes was 46% in Norway and 64% in the US (1997). This result was applicable only to patients with peripheral arterial disease Fontaine stage IV (N= 190, multivariate HR = 1.75 for all-cause mortality, P= 0.006). Angiotensin II is stimulated and results in constriction of the efferent arteriole of the glomerulus, which results in increased glomerular capillary pressures. Polyarteritis nodosa (predominant arteritis without significant glomerulonephritis, may manifest as glomerulosclerosis in hypertensive patients). The effects of vitamin D on the bone and elsewhere can be evaluated at the molecular level by examining knockout mice and are reviewed by Bouillon et al. In Catalonia, the incidence rate of ESRD due to diabetes among the general population of people with diabetes mellitus decreased from 645.6 p.m.p. in 2002 to 600 p.m.p.

in 2010. This result confirms other recent data reports. In Finland, Finne et al. About 20–30% of patients with type I or type II diabetes develop evidence of nephropathy (3). Having even a small amount of albumin in your urine is a sign that early kidney damage is present. [9] showed that from 1996 to 2006 the overall incidence of ESRD due to diabetes as the primary renal disease decreased at an average rate of 2.9% per year among the US diabetes population. In order to keep caloric intake up, what do people substitute for protein?

[10] have also shown that age-specific incidence rates in most groups have stabilized in the past 2–5 years. A variety of factors may explain the paradox of a decrease in the incidence of ESRD due to diabetes at the same time as diabetes prevalence is increasing in the general population. A number of interesting questions remain. The number of patients with diabetes who reach ESRD is continuing to increase [11], or, from a more optimistic perspective, beginning to stabilize [10, 12]. In other words, the number of diabetic ESRD patients is increasing more slowly than the number of diabetic patients in the general population, a result that will lead to a decrease in the ESRD incidence rate over time in the diabetic population. This difference in trends between the general and ESRD populations may indicate improvements in the care of diabetic patients under treatment with renin–angiotensin system inhibitors and the aggressive glycaemic control available since 1980 [13]. Nevertheless, studies of care for patients with chronic kidney disease at early stages underline that improvement is still necessary for patients with type 2 diabetes and hypertension [14, 15].

The immunostaining was quantitated by counting the number of positive cells in 20 glomeruli and 20 grid fields (0.1 mm2)4. The decrease in incidence might, therefore, be related to a higher proportion of patients who choose not to be treated or who are not referred to a dialysis unit. Renal replacement therapy registries do not provide estimates of these groups of patients. Epidemiological studies based on diabetes as the primary renal disease must be interpreted with caution [16, 17]. Renal biopsies are performed in fewer than 10–20% [12, 18] of these patients; nephrologists determine the primary nephropathy by clinical evaluation. In European countries, about 30–40% of incident ESRD patients have diabetes as an associated co-morbidity, but only 20% have a diagnosis of diabetic nephropathy [12, 19–21]. One-third of type 2 diabetic patients with proteinuria have histological involvement unrelated to diabetic nephropathy, and multiple diseases are possible [22].

Renal crisis affects about 10% of patients with systemic sclerosis. Taken together, these studies suggest that receptor-mediated vitamin D actions in part via the RAS may provide renoprotection in diabetic nephropathy. Variations among nephrologists on reporting this primary renal disease can vary from a conservative approach (diabetic nephropathy only with a renal biopsy or strong evidence such as a high level of proteinuria or associated diabetic retinopathy) to a simplistic approach (coding diabetic nephropathy when diabetes is present). A decline in disease-specific incidence of diabetes-related ESRD among diabetic patients might thus reflect changes in diagnostic attribution over time rather than a true change in the rate of progression to diabetic nephropathy. Moreover, great variations may exist among countries: diabetes was reported as a primary renal disease in only 56% of incident ESRD patients with associated type 2 diabetes in the French Renal Epidemiology and Information Network (REIN) Registry in 2010 [12], but also in 74.1% of such patients in the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry in 1991–2005 [23]. A trend towards a more specific approach in coding the underlying nephropathy may also play a role in explaining the decreased incidence rate of diabetes-related ESRD over time. Further support for the results of Comas et al.

could usefully come from studies that take into account the type of diabetes, the trends in the underlying general population and the evaluation of preventive care in the diabetic population. The differences in patient characteristics by type of diabetes and relative changes in the incidence and prevalence of diabetes in the general population and in the incidence of ESRD associated with diabetes are not likely to vary consistently between type 1 and type 2 diabetic patients over time. It is, therefore, important that epidemiology studies in ESRD populations include consideration of diabetes both as a cause of renal disease and as an associated condition or co-morbidity and that type 1 and type 2 diabetic patients be distinguished, in view of their different aetiology, management options and prognosis [23]. As you can see, the results of each subject are presented a single line. For example, in France, between 2007 and 2011, the number of incident patients with diabetes type 2 increased by 20.9% compared with 6.7% in non-diabetic patients. Figure 1 shows the different components of the difference. In diabetic type 2 patients, an increase of 3.3% can be attributed to the aging of the general population, 2.2% to the increase in the population size and 15.4% to residual effects related to the disease.

In non-diabetic patients, an increase of 3.1% can be attributed to the aging of the general population, 2.0% to the increased population size and only 1.6% to the residual disease-related effect. This difference in the residual effect confirms the persistent impact of diabetes on ESRD incidence. In conclusion, the reassuring results reported by Comas et al. must now be confirmed in other European populations. Epidemiologic studies are needed to improve our understanding of the decrease in ESRD in the diabetic population. After the decrease of cardiovascular mortality in patients with diabetes and ESRD is confirmed, correlation studies would be useful to evaluate the diffusion of preventive treatments such as renin–angiotensin system inhibitors.

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