Objective: Renal 11b-hydroxysteroid dehydrogenase type 2 (11b-HSD2) enables selective access of aldosterone to the mineralocorticoid receptor (MR). Impaired 11b-HSD2 activity has been suggested in patients with hypertension as well as in patients with renal disease, where it may contribute to sodium retention, oedema and hypertension. To date, these studies have relied upon urinary cortisol (F) metabolite levels as surrogate markers of renal 11b-HSD2 activity. Methods: We have directly analysed renal 11b-HSD2 mRNA expression in 95 patients undergoing kidney biopsy using TaqMan real-time PCR. Serum and 24-h urine samples were used to document underlying renal function and endocrine parameters. Urinary F and cortisone (E) metabolites were analysed using gas chromatography/mass spectrometry. Results: Expression of 11b-HSD2 did not correlate with blood pressure or urinary Na/K ratio, but a significant positive correlation with creatinine clearance was observed (r ¼ 0.284; P , 0.01). Immunofluorescence and confocal laser microscopy confirmed decreased 11b-HSD2 expression in patients with impaired renal function. For the first time, we showed that 11b-HSD2 mRNA expression correlated negatively with the urinary free (UF) F/E (UFF/UFE) ratio (r ¼ 0.276; P , 0.05) as well as with the urinary tetrahydrocortisol þ 5a-tetrahydrocortisol/tetrahydrocortisone ((THF þ aTHF)/THE) ratio (r ¼ 0.256; P , 0.05). No difference in 11b-HSD2 mRNA expression or in the UFF/UFE ratio was found between groups with no proteinuria, microalbuminuria, moderate or severe proteinuria. In contrast, the urinary (THF þ aTHF)/THE ratio increased significantly (P , 0.05) in patients with severe albuminuria, suggesting increased hepatic 11b-HSD1 in those patients. Conclusions: These data suggest that renal 11b-HSD2 expression may be represented only marginally better, if at all, by the UFF/UFE than by the (THF þ aTHF)/THE ratio. Reduced renal 11b-HSD2 expression may lead to occupancy of the MR by glucocorticoids such as cortisol and may contribute to the increased sodium retention seen in patients with impaired renal function.European Journal of Endocrinology 153 291-299
LAGB gave therapeutic success (progressive and significant weight loss). Psychotherapy was not only a simple support to diet but also an important part of the multidiscipline treatment. For best results, the team must care for patients individually and not just follow the same fixed protocol.
Aims
According to cardiovascular outcome trials, some sodium‐glucose contransporter‐2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real‐world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP‐1RA as second or a more advanced line of therapy.
Materials and methods
DARWIN‐T2D was a retrospective multi‐centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP‐1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow‐up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM).
Results
Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP‐1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow‐up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP‐1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin.
Conclusion
In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP‐1RA for attainment of combined risk factor goals.
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