Sex hormone levels are not associated with progression of renal disease in male patients with T2DM.

BACKGROUND: Greater renal function decline (RFD) in type 2 diabetes (T2DM) has been suggested in men compared with women, and imbalances in estrogen/androgen levels have been associated with cardiovascular disease mortality in elderly men, but it remains unclear whether sex hormone disequilibrium is related to diabetic nephropathy (DN) in men with T2DM. OBJECTIVE: This study examined the relationship between sex steroid concentrations and renal outcomes in male T2DM patients. POPULATION AND METHODS: Total testosterone (T), total estradiol (E2), sex hormone-binding globulin (SHBG), and total and calculated free (cf) E2/T ratios were compared in 735 male T2DM patients with (n=513) and without (n=222) DN, using a cross-sectional approach. Also, in a pilot complementary prospective nested case-control cohort, total E2/total T and cfE2/cfT were evaluated according to a hard renal outcome (HRO): end-stage renal disease/doubling of baseline serum creatinine (36 HRO cases, 72 HRO controls) and rate of eGFR decline (68 rapid vs 68 slow RFD). RESULT: With the cross-sectional approach, E2 and cfE2 were higher in DN cases vs DN controls (95.5 vs 86.8pmol/L [P=0.0246] and 2.59 vs 2.36pmol/L [P=0.005], respectively). The difference in E2 persisted on multivariate analysis. In the prospective approach, E2 and T concentrations, and total E2/total T and cfE2/cfT2 ratios did not differ in HRO cases vs controls or in patients with rapid vs slow RFD. CONCLUSION: Although positively related to DN in the cross-sectional analysis, progression of renal disease in male patients with T2DM was not related to either sex hormone levels or aromatase index as reflected by E2/T ratio.

The influence of sex on renal function decline in people with Type 2 diabetes.

AIMS: Several reports have suggested a relationship between male sex and albuminuria in Type 2 diabetes, but impact on renal function decline has not been established. Our aim was to describe the influence of sex on renal function decline in Type 2 diabetes. METHODS: SURDIAGENE, an inception cohort, consisted in 1470 people with Type 2 diabetes. Patients without renal replacement therapy and with ≥ 3 serum creatinine determinations during follow-up prior to end-stage renal disease were included in the study. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Primary outcome was steep estimated glomerular filtration rate (eGFR) decline, defined as a yearly slope value lower than -3.5 ml min(-1) 1.73 m(-2). Secondary outcomes were estimated glomerular filtration rate trajectories according to sex and occurrence of end-stage renal disease. RESULTS: A total of 22 914 serum creatinine determinations were considered in 1146 participants (60% men), aged 65 ± 11 years, with a median follow-up duration of 5.7 years (range 0.1-10.2). Median yearly estimated glomerular filtration rate slope was -1.31 ml min(-1) 1.73 m(-2) in women and -1.77 ml min(-1) 1.73 m(-2) in men (P < 0.001). Men were more likely than women to develop end-stage renal disease (22 men vs. 7 women; P(log-rank) = 0.03). Male sex was an independent risk factor of steep estimated glomerular filtration rate decline [adjusted odds ratio = 1.33 (1.02-1.76), P = 0.04] after adjustment for age, time from diagnosis of Type 2 diabetes, glycated haemoglobin, systolic blood pressure and urinary albumin:creatinine ratio. A multivariable linear mixed-effects model showed a significant difference of estimated glomerular filtration rate trajectories between men and women (P < 0.001). CONCLUSION: Male sex is an important independent factor associated with renal function decline in Type 2 diabetes.

Pharmacokinetics of colistin and colistimethate sodium after a single 80-mg intravenous dose of CMS in young healthy volunteers.

Colistin pharmacokinetics (PK) was investigated in young healthy volunteers after a 1-h infusion of 80 mg (1 million international units (MIU)) of the prodrug colistin methanesulfonate (CMS). Concentration levels of CMS and colistin were determined in plasma and urine using a new chromatographic assay and analyzed simultaneously with a population approach after correcting the urine-related data for postexcretion hydrolysis of CMS into colistin. CMS and colistin have low volumes of distribution (14.0 and 12.4 liters, respectively), consistent with distribution being restricted to extracellular fluid. CMS is mainly excreted unchanged in urine (70% on average), with a typical renal clearance estimated at 103 ml/min-close to the glomerular filtration rate. Colistin elimination is essentially extrarenal, given that its renal clearance is 1.9 ml/min, consistent with extensive reabsorption. Colistin elimination is not limited by the formation rate because its half-life (3 h) is longer than that of CMS. The values of these pharmacokinetic parameters will serve as reference points for future comparisons with patients' data.

To what extent should we lower HbA1c in diabetic subjects?

Current recommendations regarding glycemic control suggest that HbA(1c) should be lower than 6.5%. This is supported by data regarding microvascular disease, namely retinopathy rather than nephropathy. The question is not completely solved regarding cardiovascular diseases, where a strategy of very low HbA(1c) ("the lower the better") is expected to be effective. Some ongoing studies will help to answer these unsolved questions.