Diabetes, Obesity & Metabolism最新文献

Aims: This study aimed to identify key factors with the greatest influence on glycaemic outcomes in young individuals with type 1 diabetes (T1D) and very elevated glycaemia after 3 months of automated insulin delivery (AID).

Materials and methods: Data were combined and analysed from two separate and previously published studies with similar inclusion criteria assessing AID (MiniMed 780G) efficacy among young individuals naïve to AID (aged 7-25 years) with glycated haemoglobin A1c (HbA1c) ≥69 mmol/mol (≥8.5%). Univariate and multivariate linear models were performed to explore factors leading to the greatest improvements in HbA1c and time in range 3.9-10.0 mmol/L (70-180 mg/dL; TIR).

Results: A total of 99 young individuals (aged 17.3 ± 4.2 years; baseline HbA1c 92 ± 21 mmol/mol [10.6% ± 1.9%]) were included. After 3 months of AID use, HbA1c improved to 65 ± 16 mmol/mol (8.1% ± 1.5%) (-27 ± 23 mmol/mol; -2.5% ± 2.1% change), and TIR improved from 24.2% ± 13.5% to 58.4% ± 15.4% (p both <0.001). In the multivariate analysis, two key factors for both HbA1c and TIR improvement were identified: high baseline HbA1c (>100 mmol/mol [>11.0%]) and high time in automation mode (>80%), which led to decreased HbA1c by 27.0 mmol/mol (2.4%) and 14.2 mmol/mol (1.3%) and increased TIR by 6.1% and 11.1% (p all <0.05) respectively. Meal announcement frequency >3 times/day and glucose target of 5.5 mmol/L (100 mg/dL) also led to significant increases in TIR. No other factors, including age, prior use of multiple daily injection, ethnicity, gender and optimal active insulin time 2 h, contributed to statistically significant HbA1c or TIR improvement.

Conclusions: In young individuals naive to AID, those with the highest baseline HbA1c and high percentage time in automation experience the greatest benefits after initiation of AID. Sociodemographic background and carbohydrate counting adherence/knowledge should not prevent or delay access to AID technology (ACTRN12621000556842 and ACTRN12622001454763).

Aim: To describe the effects of Glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with familial partial lipodystrophy (FPLD) assessed in a real-life setting in a national reference network.

Patients and methods: We retrospectively collected clinical and metabolic parameters in patients with FPLD in the French lipodystrophy reference network, who initiated GLP-1RA. Data were recorded before, at one-year (12 ± 6 months) and at the latest follow-up on GLP-1RA therapy (≥18 months).

Results: Seventy-six patients (89.4% of women), diagnosed with LMNA-related FPLD2 (n = 57), PPARG-related FPLD3 (n = 4), PLIN1-related FPLD4 (n = 5) or FPLD1 (n = 10) initiated GLP-1RA therapy between 2008 and 2024. Patients were aged a median (IQR) 48 years (34.5-57), body mass index (BMI) was 26.0 kg/m² (23.9-29.5), HbA1c 8.3% (7.5-9.3), triglycerides 2.31 mmol/L (1.62-3.88). GLP-1RA were used in addition to previously used antidiabetics, 50% of patients being insulin-treated. After one year with GLP-1RA therapy, BMI, HbA1c and triglycerides significantly decreased to 25.6 kg/m² (22.7-29.1), 7.3% (6.6-8.3) and 1.97 mmol/L (1.5-3.2) respectively (p < 0.001, p < 0.001 and p < 0.01, respectively), without significant changes in other antidiabetic and lipid-lowering drugs. Gamma-glutamyl-transferase and alanine-aminotransferase levels also significantly decreased. Effects on HbA1c, BMI and triglycerides persisted in the long term. One case of acute pancreatitis occurred during follow-up, associated with severe hypertriglyceridemia in a non-observant patient. Gastrointestinal symptoms affected 34% of patients, leading to GLP-1RA withdrawal in six patients.

Conclusion: GLP-1RA significantly improved BMI, HbA1c and triglycerides in a large majority of patients with FPLD. Larger and prospective controlled studies are warranted for identification of predictive factors and safety.

Aims: Recommendations on the use of newer type 2 diabetes (T2D) treatments (e.g., SGLT2 inhibitors and GLP-1 receptor agonists [RA]) in contemporary clinical guidelines necessitate a change in how T2D models approach therapy selection and escalation. Dynamic, person-centric clinical decision-making considers factors beyond a patient's HbA1c and glycaemic targets, including cardiovascular (CV) risk, comorbidities and bodyweight. This study aimed to update the existing Cardiff T2D health economic model to reflect modern T2D management and to remain fit-for-purpose in supporting decision-making.

Materials and methods: The Cardiff T2D model's therapy selection/escalation module was updated from a conventional, glucose-centric to a holistic approach. Risk factor progression equations were updated based on UKPDS90; the cardio-kidney-metabolic benefits of SGLT2i and GLP-1 RA were captured via novel risk equations derived from relevant outcomes trial data. The significance of the updates was illustrated by comparing predicted outcomes and costs for a newly diagnosed T2D population between conventional and holistic approaches to disease management, where the latter represents recent treatment guidelines.

Results: A holistic approach to therapy selection/escalation enables early introduction of SGLT2i and GLP-1 RA in modelled pathways in a manner aligned to guidelines and primarily due to elevated CV risk. Compared with a conventional approach, only considering HbA1c, patients experience fewer clinical events and gain additional health benefits.

Conclusions: Predictions based on a glucose-centric approach to therapy are likely to deviate from real-world observations. A holistic approach is more able to capture the nuances of contemporary clinical practice. T2D modelling must evolve to remain robust and relevant.

Aim: To explore the effects of sex and baseline body mass index (BMI) on the efficacy and safety of survodutide in people with a BMI ≥27 kg/m².

Materials and methods: Totally 387 people (aged 18-75 years, BMI ≥27 kg/m², without diabetes) were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.4, 3.6 or 4.8 mg) or placebo for 46 weeks (20-week dose escalation; 26-week dose maintenance). Participants were categorized according to sex and baseline BMI. Data were analysed descriptively for the full analysis set (FAS), according to dose assigned at randomization (planned treatment) using on-treatment data or all data censored for COVID-19-related treatment discontinuations. (ClinicalTrials.gov number: NCT04667377).

Results: After 46 weeks of survodutide treatment, females had greater reductions in bodyweight and waist circumference than males. Participants with a lower baseline BMI had greater proportional reductions in bodyweight than those with a higher baseline BMI; the trend was reversed for reductions in waist circumference. Rates of adverse events (AEs) were comparable between subgroups for sex and baseline BMI. Nausea was the most frequently reported gastrointestinal AE in all subgroups.

Conclusions: In people with a BMI ≥27 kg/m², survodutide was associated with clinically meaningful reductions in bodyweight and waist circumference when compared with placebo, in prespecified subgroups based on sex and baseline BMI, and was tolerated at all doses tested.

Background/aims: The prognostic importance of changes in vibration-controlled transient elastography (VCTE) parameters, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP), in individuals with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown.

Methods: A prospective cohort of 288 patients underwent 2 VCTE exams at least 2 years apart, and the relative percentage changes in LSM and CAP were calculated. Outcomes were the occurrence of any liver-related events (LREs), cardiovascular events (CVEs), and all-cause mortality. Multivariable Cox analyses, adjusted for liver and cardiometabolic factors, assessed associations between VCTE parameters changes, both as continuous and dichotomical variables (LSM increase >15% and CAP reduction >10%), and outcomes.

Results: During a median follow-up of 6 years, there were 22 LREs, 28 CVEs, and 37 all-cause deaths. For LREs, baseline LSM was the strongest predictor, but LSM increases added further prognostic value (hazard ratio [HR]: 1.5 [1.0-2.1], 1-SD increment). For CVEs, both LSM increase (HR: 1.7 [1.3-2.3]) and CAP reduction (HR: 1.5 [1.0-2.3], 1-SD decrease) were significant predictors. For all-cause mortality, baseline CAP was a protective predictor. When classified into subgroups based on LSM and CAP changes, the subgroup with both increased LSM and reduced CAP had the highest risks for CVEs (HR:5.3 [1.4-19.6]) and all-cause mortality (HR: 3.4 [1.2-9.6]). The highest risk for LREs was observed in the subgroup with increased LSM without CAP reduction (HR: 3.5 [0.9-12.9]).

Conclusions: VCTE parameters changes, LSM increase and CAP reduction, provide prognostic information for adverse liver, cardiovascular, and mortality outcomes in individuals with T2D and MASLD.

Background: Metabolic-bariatric surgery (MBS) transcends weight loss and offers wide-ranging health benefits, including positive effects on brain function. However, the mechanisms behind these effects remain unclear, particularly in the context of significant postoperative changes in the inflammatory profile characteristic of MBS. Understanding how inflammation influences postoperative brain function can enhance our decision-making on patient eligibility for MBS and create new opportunities to improve the outcomes of this popular treatment.

Objective: To identify brain regions where spontaneous neural activity and functional connectivity are linked with the evolving inflammatory profile following MBS.

Methods: We investigated the relationship between the perioperative ratio of interleukin (IL)-6 to IL-10 and both the amplitude of low-frequency fluctuation (ALFF) and functional connectivity across 375 brain regions. We examined 36 patients at three time points: 1 week before, and 3 and 12 months after laparoscopic sleeve gastrectomy.

Results: Initially, the IL-6/IL-10 ratio increased during the early postoperative period but then decreased to levels lower than the preoperative values 1 year after surgery. We observed that ALFF in four subcortical structures decreased with a rising IL-6/IL-10 ratio and increased with a declining ratio. Conversely, 16 cortical regions displayed the opposite trend. Additionally, functional connectivity between the left insula and bilateral medial prefrontal cortex increased with a rising IL-6/IL-10 ratio and decreased with a declining ratio.

Conclusions: Our study is the first to identify brain regions significantly linked to inflammation after MBS. Importantly, many of the discovered areas were previously shown to be involved in the pathogenesis of obesity or are targets of contemporary medical treatments. Consequently, our findings offer valuable insights for future obesity research, especially in the context of potential therapeutic opportunities.

Background: Medications targeting the leptin and Apolipoprotein CIII (APOC3) pathways are currently under development for the treatment of hypertriglyceridaemia. Given that both pathways are implicated in triglyceride regulation, it is unknown whether they function independently or interact under physiological conditions and under acute or long-term energy deficiency.

Methods: APOC3 levels and their association with circulating lipids and lipoproteins were evaluated in the context of two randomised controlled studies. In Study-1, 15 healthy individuals were examined under three distinct conditions, each lasting 72 h: isocaloric feeding, fasting with placebo administration and fasting with leptin administered at replacement doses. In Study-2, 20 females with hypoleptinemia due to relative energy deficiency in sport (REDs) for a minimum of 6 months were treated with either leptin or a placebo for 36 weeks.

Results: In Study-1, APOC3 levels remained stable across all arms and were unaffected by leptin administration. In the fed state, APOC3 levels presented positive correlations with various VLDL, IDL, LDL and HDL sizes, and free fatty acids (FFA), most of which were not replicated in fasting. During complete energy deprivation, APOC3 was correlated with HDL molecules, glutamine and FFA, whereas its levels were positively associated only with FFA under leptin treatment. In Study-2, APOC3 levels were lower in the leptin group, but this was not a leptin-dependent effect. A positive correlation between APOC3 levels and HDL was observed in the leptin group.

Conclusions: These results contribute towards our better understanding of the intricate nature of lipid regulation under energy deficiency, suggesting that medications targeting the leptin and APOC3 pathways act through different metabolic pathways and thus may have independent effects from each other in regulating triglycerides.

Background: Diabetic kidney disease (DKD) makes up nearly half of all chronic kidney disease cases and is a major cause of mortality for people with diabetes. However, the study of the association of longitudinal Chinese visceral adiposity index (CVAI) with DKD is still missing.

Methods: This prospective cohort study included 7874 diabetes patients from the Kailuan study. These participants had complete repeated waist circumference, body mass index, triglycerides and high-density lipoprotein cholesterol measurements that formed the continuous CVAI records. DKD was defined by increased proteinuria or decreased estimated glomerular filtration rate (eGFR), preceded by diabetes. Cox proportional hazard regression models were used to examine the associations between baseline and cumulative CVAI and the risk of DKD.

Results: There is a positive association between the CVAI level, whether baseline or cumulative, and the incidence of DKD among diabetic patients (p for log-rank tests <0.001). Compared to low CVAI level, the high baseline CVAI level was positively associated with the risk of DKD (HR: 1.24, 95% CI: 1.09-1.42), as well as the high cumulative CVAI level (HR: 1.62, 95% CI: 1.29-2.04). In addition, the assumption of linearity for the positive associations between both baseline (P-nonlinear = 0.264, p for overall <0.001) and cumulative (P-nonlinear = 0.765, p for overall <0.001) CVAI with incident DKD was satisfied.

Conclusions: Higher baseline and cumulative CVAI are associated with a higher risk of DKD. This finding suggests the health benefits of low levels of CVAI and the importance of its regular surveillance among individuals with diabetes.

Background & aims: This study assessed the association of remission of type 2 diabetes mellitus (DM) or metabolic dysfunction-associated steatotic liver disease (MASLD)/related SLD (r-SLD; MASLD with excessive alcohol intake) as defined by the fatty liver index with the risk of cardiovascular disease (CVD).

Methods: Health examination data at baseline and after 2 years (2-Years) were extracted from a nationwide claims database in Japan. Among participants aged 18-72 years with at least 3 years of follow-up, 9345 participants with DM-associated MASLD/r-SLD and 71 932 participants with non-DM MASLD/r-SLD at baseline were included in the study. The participants were stratified by the achievement of remission of MASLD/r-SLD or DM at 2-Years. In each group after stratification, the risk of new-onset CVD during the observation period was analysed using multivariate Cox proportional hazards models.

Results: During a median follow-up of 4.9 years (starting from 2-Years), 1368 cases of CVD were observed. The hazard ratio (95% confidence interval) for CVD was 0.50 (0.31-0.80) for participants with remission of DM, 0.65 (0.47-0.91) for participants with remission of MASLD/r-SLD, and 0.34 (0.15-0.77) for participants with remission of both DM and MASLD/r-SLD. Conversely, remission of MASLD/r-SLD was not linked to a reduced risk of CVD in participants with non-DM MASLD/r-SLD.

Conclusion: The association of MASLD/r-SLD remission with CVD risk differs greatly in the presence and absence of DM. In patients with DM-MASLD/r-SLD, MASLD/r-SLD remission can significantly reduce CVD risk similarly as remission of DM.