Testosterone deficiency is common in men with diabetes, regardless of the type. Testosterone levels are partly influenced by insulin resistance, which may represent an important avenue for intervention, whereas the utility of testosterone replacement remains to be established in prospective trials.

OBJECTIVE -To determine the prevalence and characteristics of patients with type 2 diabetes who have impaired renal function, defined as a glomerular filtration rate (GFR) Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , and normoalbuminuria. RESEARCH DESIGN AND METHODS-A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic 99m Tcdiethylene-triamine-penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria.RESULTS -A total of 109 patients (36%) had a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 . The overall prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109 (35%), and 28 of 109 (26%), respectively. Compared with patients with macroalbuminuria, those with normoalbuminuria were more likely to be older and female. After excluding patients whose normoalbuminuric status was possibly related to the initiation of a renin-angiotensin system (RAS) inhibitor before the start of the study, the prevalence of a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2and normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%) unselected patients with impaired renal function were available for comparison over a 3-to 10-year period. The rates of decline in GFR (ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 ⅐ year Ϫ1 ) of Ϫ4.6 Ϯ 1.0, Ϫ2.8 Ϯ 1.0, and Ϫ3.0 Ϯ 07 were not significantly different for normo-(n ϭ 12), micro-(n ϭ 12), and macroalbuminuric (n ϭ 10) patients, respectively.CONCLUSIONS -These results suggest that patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric. Diabetes Care 27:195-200, 2004A reduced glomerular filtration rate (GFR), mainly estimated from creatinine clearance measurements, has been reported to occur in some longstanding normoalbuminuric type 1 diabetic patients (1,2). Work from our group has suggested that this phenomenon can also occur in both type 1 or type 2 diabetes and that it may be more common in type 2 diabetes (3). Furthermore, in comparison to patients with type 1 diabetes, albuminuric patients with type 2 diabetes have a great deal of renal ultrastructural heterogeneity (4,5). This structural heterogeneity raises the possibility that different GFR and AER relationships are seen in patients with type 2 compared with those with type 1 diabetes. We have therefore further investigated the association between GFR and AER in patients with type 2 diabetes. In particular, we determined the prevalence and characteristics of patients with impaired renal function, defined as a GFR Ͻ60 ml ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 , and an AER within the normoalbuminuric range. RESEARCH DESIGN ANDMETHODS -A total of 625 patients attending the diabetes clinic at Austin Health, a tertiary referral center and teaching hospital of The University of Melbourne, Victoria, Australia, were studied between 1990 and 2001 as part of an ongoing project investigating the pathogenesis of diabetic renal disease. Isotopic estimations o...

Diabetic nephropathy (DN) is a progressive kidney disease, a well-known complication of long-standing diabetes. DN is the most frequent reason for dialysis in many Western countries. Early detection may enable development of specific drugs and early initiation of therapy, thereby postponing/preventing the need for renal replacement therapy. We evaluated urinary proteome analysis as a tool for prediction of DN. Capillary electrophoresis–coupled mass spectrometry was used to profile the low–molecular weight proteome in urine. We examined urine samples from a longitudinal cohort of type 1 and 2 diabetic patients (n = 35) using a previously generated chronic kidney disease (CKD) biomarker classifier to assess peptides of collected urines for signs of DN. The application of this classifier to samples of normoalbuminuric subjects up to 5 years prior to development of macroalbuminuria enabled early detection of subsequent progression to macroalbuminuria (area under the curve [AUC] 0.93) compared with urinary albumin routinely used to determine the diagnosis (AUC 0.67). Statistical analysis of each urinary CKD biomarker depicted its regulation with respect to diagnosis of DN over time. Collagen fragments were prominent biomarkers 3–5 years before onset of macroalbuminuria. Before albumin excretion starts to increase, there is a decrease in collagen fragments. Urinary proteomics enables noninvasive assessment of DN risk at an early stage via determination of specific collagen fragments.

Glomerular filtration rate is commonly elevated in early diabetes and patients with this symptom are arbitrarily considered to have hyperfiltration. The prevalence of hyperfiltration in type 1 diabetes varies from less than 25% to more than 75%. The corresponding figures in type 2 diabetes are significantly lower, ranging between 0% and more than 40%. Several factors, methodological and biological, may contribute to the wide variation in estimates of hyperfiltration prevalence. Methodological differences in measurement and evaluation of GFR apply in particular to the handling of plasma disappearance curves of filtration markers. Biological factors that may influence GFR in the hyperfiltration range include glycaemic control, diabetes duration, BMI, sex, pubertal status in type 1 diabetes and age in type 2 diabetes. Hyperglycaemia may influence GFR and albuminuria, and may therefore confound the evaluation of hyperfiltration as an independent risk factor for diabetic nephropathy. Adequate assessment of the relationship between glycaemic control, GFR and AER therefore requires serial measurements of all three variables followed by multivariate analysis. A recent meta-analysis of ten type 1 diabetes studies concluded that the presence of hyperfiltration at baseline more than doubled the risk of developing micro-or macroalbuminuria at follow-up. However, not all studies allowed for confounding factors or regression dilution bias. Future studies will therefore need to address the independent role of hyperfiltration, not only in the evolution of albuminuria, but also in the subsequent decline of GFR.