The use of SGLT2 inhibitors in achieving glycaemic control in maturity-onset diabetes of the young type 3.

SUMMARY: Maturity-onset diabetes of the young type 3 (MODY3) accounts for approximately 50% of cases of MODY. First-line treatment with sulfonylureas has been well established for individuals with MODY3. In contrast, the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors in the treatment of individuals with MODY3 remains unclear. This case illustrates the in vivo effect of an SGLT2 inhibitor in a 30-year-old woman with MODY3 with poor glycaemic control despite the treatment with supramaximal doses of sulfonylurea and metformin. The addition of a SGLT2 inhibitor resulted in a rapid improvement in glycaemic control without any hypoglycaemic episodes. This case suggests that SGLT2 inhibitors may be an effective and potent treatment option in addition to sulfonylureas for individuals with MODY3. LEARNING POINTS: Maturity-onset diabetes of the young type 3 (MODY3) arises from mutations in the hepatocyte nuclear factor-1alpha gene, which controls the expression of sodium-glucose co-transporter 2 (SGLT2) in the kidneys. Paradoxically, despite individuals with MODY3 having reduced expression of SGLT2, SGLT2 inhibitors induce higher glycosuria in individuals with MODY3 compared to individuals with type 2 diabetes mellitus. SGLT2 inhibitors may be an effective treatment for achieving glycaemic control in individuals with MODY3.

Impact of supplemental private health insurance on dialysis and outcomes.

BACKGROUND: The influence of health insurance systems on the treatment of end-stage kidney disease (ESKD) patients ispoorly understood. AIM: We investigated how supplemental private health insurance (PHI) coverage impacted ESKD treatment modalitiesand patient outcomes. The influence of health insurance systems on the treatment of end-stage kidney disease (ESKD) patients is poorly understood. We investigated how supplemental private health insurance (PHI) coverage impacted ESKD treatment modalities and patient outcomes. METHODS: All adult patients commencing ESKD treatment in New South Wales, Australia from 2000 to 2010 were identified using the Australia and New Zealand Dialysis and Transplant Registry. Data were linked to the state hospitalisation dataset to obtain insurance status, allowing the comparisons of mortality, ESKD treatment modality and health service utilisation between privately insured and public patients. RESULTS: The cohort of 5737 patients included 38% (n = 2152) with PHI. At 1 year after ESKD treatment initiation, PHI patients had lower mortality (hazard ratio 0.84, 95% confidence interval (CI) 0.74-0.95, P = 0.01), were more likely to be receiving home haemodialysis (HD) (odds ratio (OR) 1.38, 95% CI 1.01-1.89, P = 0.04), to have been transplanted (OR 1.75, 95% CI 1.25-2.46, P = 0.001) and used fewer hospital days (incidence rate ratio 0.85, 95% CI 0.74-0.96, P = 0.01). After adjustment, PHI patients were more likely to initiate ESKD treatment with facility-based HD (OR 1.22, 95% CI 1.01-1.46, P = 0.03) but were less likely to be started on peritoneal dialysis (OR 0.81, 95% CI 0.67-0.98, P = 0.03). CONCLUSION: Our findings suggest that supplemental PHI in Australia is associated with lower-risk ESKD treatment attributes and improved health outcomes. A greater understanding of the treatment pathways that deliver these outcomes may inform treatment for the broader ESKD treatment population.

Mitral valve surgery and coronary artery bypass grafting for moderate-to-severe ischemic mitral regurgitation: Meta-analysis of clinical and echocardiographic outcomes.

OBJECTIVE: This meta-analysis was conducted to compare clinical and echocardiographic outcomes following isolated coronary artery bypass grafting (CABG) versus CABG and mitral valve (MV) surgery in patients with moderate-to-severe ischemic mitral regurgitation (IMR). METHODS: Seven databases were systematically searched to identify relevant studies. For eligibility, studies were required to report on the primary endpoint of perioperative or late mortality. Data were analyzed according to predefined clinical endpoints. RESULTS: Four randomized controlled trials (RCTs) (n = 505) and 15 observational studies (OS) (n = 3785) met the criteria for inclusion. Compared with isolated CABG, concomitant CABG and MV surgery was not associated with increased perioperative mortality (RCTs: relative risk [RR] 0.89, 95% confidence interval [CI], 0.26-3.02; OS: RR 1.40, 95% CI, 0.88-2.23). CABG and MV surgery was associated with significantly lower incidence of moderate-to-severe MR at follow-up (RCTs: RR 0.16, 95% CI, 0.04-0.75; OS: RR 0.20, 95% CI, 0.09-0.48). Late mortality was similar between the surgical approaches in RCTs (hazard ratio [HR] 1.20, 95% CI, 0.57-2.53) and OS (HR 0.99, 95% CI, 0.81-1.21). There were no significant differences in echocardiographic outcomes. These results remained consistent in subgroup analyses restricted to patients with strictly moderate IMR. CONCLUSIONS: In patients with moderate-to-severe IMR, the addition of MV surgery to CABG was not associated with increased perioperative mortality. Although concomitant MV surgery reduced recurrence of moderate-to-severe MR at follow-up, this was not associated with a reduction in late mortality. Larger trials with longer follow-up duration are required to further assess long-term survival and freedom from reintervention.

A meta-analysis of mitral valve repair versus replacement for ischemic mitral regurgitation.

BACKGROUND: The development of ischemic mitral regurgitation (IMR) portends a poor prognosis and is associated with adverse long-term outcomes. Although both mitral valve repair (MVr) and mitral valve replacement (MVR) have been performed in the surgical management of IMR, there remains uncertainty regarding the optimal approach. The aim of the present study was to meta-analyze these two procedures, with mortality as the primary endpoint. METHODS: Seven databases were systematically searched for studies reporting peri-operative or late mortality following MVr and MVR for IMR. Data were independently extracted by two reviewers and meta-analyzed according to pre-defined study selection criteria and clinical endpoints. RESULTS: Overall, 22 observational studies (n=3,815 patients) and one randomized controlled trial (n=251) were included. Meta-analysis demonstrated significantly reduced peri-operative mortality [relative risk (RR) 0.61; 95% confidence intervals (CI), 0.47-0.77; I(2)=0%; P<0.001] and late mortality (RR, 0.78; 95% CI, 0.67-0.92; I(2)=0%; P=0.002) following MVr. This finding was more pronounced in studies with longer follow-up beyond 3 years. At latest follow-up, recurrence of at least moderate mitral regurgitation (MR) was higher following MVr (RR, 5.21; 95% CI, 2.66-10.22; I(2)=46%; P<0.001) but the incidence of mitral valve re-operations were similar. CONCLUSIONS: In the present meta-analysis, MVr was associated with reduced peri-operative and late mortality compared to MVR, despite an increased recurrence of at least moderate MR at follow-up. However, these findings must be considered within the context of the differing patient characteristics that may affect allocation to MVr or MVR. Larger prospective studies are warranted to further compare long-term survival and freedom from re-intervention.