Diabetologia最新文献

Aims/hypothesis: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria.

Methods: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching. The primary endpoint, change in eGFR, was analysed using mixed-effects models. Secondary endpoints included categorical eGFR-based outcomes and changes in albuminuria. Subgroup and sensitivity analyses were performed to assess robustness of the findings.

Results: After matching, 5701 participants/group were included. Participants were predominantly male, aged 61 years, with a 10 year duration of diabetes, a baseline HbA_1c of 64 mmol/mol (8.0%) and BMI of 33 kg/m². Chronic kidney disease (CKD) was present in 23% of participants. During a median of 2.1 years, from a baseline of 87 ml/min per 1.73 m², eGFR remained higher in the SGLT2i group compared with the GLP-1RA group throughout the observation period by 1.2 ml/min per 1.73 m². No differences were detected in albuminuria change. The SGLT2i group exhibited lower rates of worsening CKD class and favourable changes in BP compared with the GLP-1RA group, despite lesser HbA_1c decline. SGLT2i also reduced eGFR decline better than GLP-1RA in participants without baseline CKD.

Conclusions/interpretation: In individuals with type 2 diabetes, treatment with SGLT2i was associated with better preservation of renal function compared with GLP-1RA, as evidenced by slower decline in eGFR. These findings reinforce SGLT2i as preferred agents for renal protection in this patient population.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as the fibrosis-4 index [FIB-4]) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification-including weight loss, dietary changes, physical exercise and discouraging alcohol consumption-as well as optimal management of comorbidities-including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for type 2 diabetes or obesity, if indicated-is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Transgender identity is often associated with gender dysphoria and minority stress. Gender-affirming hormone treatment (GAHT) includes masculinising or feminising treatment and is expected to be lifelong in most cases. Sex and sex hormones have a differential effect on metabolism and CVD in cisgender people, and sex hormone replacement in hypogonadism is associated with higher vascular risk, especially in ageing individuals. Using narrative review methods, we present evidence regarding metabolic and cardiovascular outcomes during GAHT and propose recommendations for follow-up and monitoring of metabolic and cardiovascular risk markers during GAHT. Available data show no increased risk for type 2 diabetes in transgender cohorts, but masculinising GAHT increases lean body mass and feminising GAHT is associated with higher fat mass and insulin resistance. The risk of CVD is increased in transgender cohorts, especially during feminising GAHT. Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit and increased BP, while feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol. Assigned male sex at birth, higher age at initiation of GAHT and use of cyproterone acetate are separate risk factors for adverse CVD markers. Metabolic and CVD outcomes may improve during gender-affirming care due to a reduction in minority stress, improved lifestyle and closer surveillance leading to optimised preventive medication (e.g. statins). GAHT should be individualised according to individual risk factors (i.e. drug, dose and form of administration); furthermore, doctors need to discuss lifestyle and preventive medications in order to modify metabolic and CVD risk during GAHT. Follow-up programmes must address the usual cardiovascular risk markers but should consider that biological age and sex may influence individual risk profiling including mental health, lifestyle and novel cardiovascular risk markers during GAHT.

Aims/hypothesis: Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity.

Methods: This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses.

Results: We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI ≥40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups.

Conclusions/interpretation: Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality.

Aims/hypothesis: It is unclear whether kidney transplant candidates with diabetes have equitable transplantation opportunities or have divergent survival probabilities stratified by kidney replacement therapy. The aim of this study was to investigate these two issues using national transplant registry data in the UK.

Methods: A cohort study was undertaken of prospectively collected registry data of all wait-listed people with kidney failure receiving dialysis in the UK. All people listed for their first kidney-alone transplant between 2000 and 2019 were included. Stratification was done for cause of kidney failure. Primary outcome was all-cause mortality. Time-to-death from listing was analysed using adjusted non-proportional hazard Cox regression models, with transplantation handled as a time-dependent covariate.

Results: A total of 47,917 wait-listed people with kidney failure formed the total study cohort, of whom 6594 (13.8%) had diabetes classified as cause of kidney failure. People with kidney failure with diabetes comprised 27.6% of the cohort (n=3681/13,359) that did not proceed to transplantation vs only 8.4% (n=2913/34,558) of the cohort that received a transplant (p<0.001). Kidney transplant candidates with diabetes were more likely to be older, of male sex and of ethnic minority background compared with those without diabetes. In an adjusted analysis, compared with remaining on dialysis, any kidney transplant provided survival benefit for wait-listed kidney transplant candidates regardless of diabetes as cause of kidney failure (RR 0.26 [95% CI 0.25, 0.27], p<0.001).

Conclusions/interpretation: Kidney transplant candidates with diabetes have a lower chance of transplantation despite better survival after kidney transplantation vs remaining on dialysis. The reasons for this require further investigation to ensure equal transplantation opportunities.

Internationally, governments and scientists are bound by legal and treaty rights when working with Indigenous nations. These rights include the right of Indigenous people to control the conduct of science with Indigenous nations. Unfortunately, in some cases, individual scientists and scientific teams working with biological and genetic data collected from Indigenous people have not respected these international rights. Here, we argue that the scientific community should understand and acknowledge the historical harms experienced by Indigenous people under the veil of scientific progress (truth) and implement existing standards for ethical conduct of research and sovereign control of data collected within Indigenous communities (reconciliation). Specifically, we outline the rationale for why scientists, scientific journals and research integrity and institutional review boards/ethics committees should adopt, and be held accountable for upholding, current international standards of Indigenous data sovereignty and ethical use of Indigenous biological samples.