Diabetes, Obesity & Metabolism最新文献

Type 1 diabetes is recognized as a chronic disease with a presymptomatic phase that does not require insulin therapy and a clinical phase where insulin treatment becomes necessary. The presymptomatic phase is characterized by the presence of autoantibodies targeting pancreatic islet beta cell antigens (islet autoantibodies). This phase is further classified into three stages: Stage 1, defined by normoglycaemia; Stage 2, characterized by dysglycaemia; and Stage 3, marked by hyperglycaemia, which typically presents clinically and necessitates insulin therapy. The prospect of therapies to delay the onset of clinical disease and insulin treatment has been a driver of research into the presymptomatic phase since the discovery of islet autoantibodies. With the recent approval of teplizumab as a therapy to delay disease progression, attention has increasingly focused on diagnosing individuals with Stage 1 and Stage 2 type 1 diabetes. However, diagnosing an asymptomatic condition that affects fewer than 1 in 200 individuals poses significant challenges. As we enter this new era of diagnosis, it is crucial to refine diagnostic approaches to ensure accuracy and effectiveness. This review summarizes current evidence and guidance while emphasizing the need for continued research alongside broader application of screening. PLAIN LANGUAGE SUMMARY: Type 1 diabetes is an autoimmune disease that affects approximately 0.5% of individuals. In this publication, the authors provide a comprehensive overview of strategies for identifying individuals in the pre-symptomatic, early stages of the disease. Early-stage type 1 diabetes can be detected by the presence of autoantibodies against specific proteins in the blood, signaling an ongoing disease process before clinical symptoms appear. Genetic factors also contribute to the development of these autoantibodies and the disease itself. The paper explores how these markers are used for early identification, emphasizing optimal screening ages and the role of confirmation tests in preventing misdiagnosis. A key consideration in early diagnosis is that disease progression varies-some individuals develop clinical diabetes rapidly, while others may take many years. The authors discuss additional tests that can help predict how soon a diagnosed individual may require insulin treatment. Finally, the paper highlights ongoing challenges in optimizing screening for wider application and the complexities of integrating research-based screening into routine clinical practice.

Glycaemic therapy in type 1 diabetes (T1D) is focused on insulin, with the majority of studies investigating different insulin preparations, delivery devices and dosing accuracy methods. While insulin deficiency is the key mechanism for hyperglycaemia in T1D, individuals with this condition can also develop insulin resistance (IR), making optimisation of glycaemia more challenging. Importantly, IR in T1D increases the risk of both microvascular and macrovascular complications; yet, it is rarely targeted in routine clinical care. In this narrative review, we briefly discuss the mechanistic pathways for diabetes complications in individuals with T1D, emphasising the adverse role of IR. We subsequently cover the use of adjunctive glycaemic therapies for improving the metabolic profile in T1D, focusing on therapies that have possible or definite cardiovascular or renal protective properties in individuals with type 2 diabetes. These include metformin and agents in the thiazolidinedione, Sodium-Glucose Cotransporter-2 inhibitor (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) groups. In addition to reviewing the role of these agents in improving metabolic parameters, we address their potential vascular and renal protective effects in individuals with T1D. We suggest a pragmatic approach for using these agents in T1D, based on current knowledge of their benefits and risks, while also highlighting gaps in knowledge and areas that require further research. It is hoped that the review raises awareness of the role of adjunctive therapies in T1D and offers healthcare professionals simple guidance on using such agents for the management of high-risk individuals with T1D.

Aims: This study assessed the cost-effectiveness of a digital health-supported and community pharmacy-based lifestyle intervention (PRIME) programme for individuals with prediabetes in Malaysia over a 6-month period.

Materials and methods: A trial-based cost-effectiveness study with a 6-month time horizon was conducted. Ninety-one participants (intervention, n = 46; usual care, n = 45) across 13 community pharmacies were included. The intervention group received in-depth counselling from pharmacists, in-app prediabetes education modules and peer support, while the usual care group received counselling based on pharmacists' usual practice. The primary outcome was quality-adjusted life years (QALY). Incremental cost-effectiveness ratios (ICER) per QALY gained of the intervention were compared with usual care from healthcare and societal perspectives. Non-parametric bootstrapping was used to examine uncertainty.

Results: At 6months, the QALY achieved was 0.467 (95% CI 0.456 to 0.479) in the intervention group and 0.466 (95% CI 0.451 to 0.482) in the usual care group, resulting in a net gain of 0.005 QALY (95% CI -0.017 to 0.026) in the intervention group. The incremental healthcare and societal costs were US$6.10 (95% CI $5.33 to $6.88) and $10.69 (95% CI $6.03 to $15.35), respectively. From a healthcare perspective, the ICER per QALY gained was $1354, with a probability of 69.2% being cost-effective, while the corresponding figures were $2371 and 67.7% from a societal perspective. Results were below the willingness-to-pay threshold at $11 845 and were robust to sensitivity analyses.

Conclusion: A community pharmacy-based and digital health-supported lifestyle intervention to manage prediabetes may be cost-effective compared with usual care in Malaysia over a 6-month period.

Objective: To evaluate the efficacy and safety of faster-acting insulin aspart (faster aspart) compared with insulin aspart in adults with type 1 diabetes (T1D) using a non-automated insulin pump and continuous glucose monitoring (CGM).

Methods: This double-blinded crossover study randomly assigned participants to start with either faster aspart or insulin aspart for 16 weeks, followed by a 3-week washout period, then switching to the alternate therapy for another 16 weeks. Insulin pump settings were adjusted every 3 weeks. The primary outcome was time in range (TIR: 3.9-10.0 mmol/L). Secondary outcomes included other CGM metrics and HbA1c.

Results: Forty adults (20 males) with a median age of 54 years, T1D duration of 27 years, and HbA1c of 59 mmol/mol (7.5%) were included. At the study end, TIR was (mean ± SD) 60.6 ± 12.1% for insulin aspart and 62.5 ± 12.3% for faster aspart, p = 0.24 (primary endpoint). The baseline-adjusted estimated treatment difference (ETD) for TIR was 6.0% (95%CI: 2.2;9.9), p = 0.002; time above range (>10.0 mmol/L) was -5.7% (-9.8; -1.6), p = 0.007; and time below range (<3.9 mmol/L) was -0.4% (-1.1;0.4), p = 0.30-all in favour of faster aspart. Faster aspart significantly improved the coefficient of variation (34.0 ± 3.7% vs. 35.9 ± 4.9%, p = 0.02) and the HbA1c levels (ETD -1.9 (-3.7; -0.2) mmol/mol or - 0.18% (-0.34;-0.02), p = 0.03). No significant differences were observed in severe adverse events, including severe hypoglycaemia and diabetic ketoacidosis. Faster aspart had more injection site reactions than insulin aspart (p = 0.03).

Conclusion: Faster aspart improved baseline-adjusted TIR, TAR, CV and HbA1c after 16 weeks with frequent insulin pump adjustments but had a higher incidence of injection site reactions.

Aims: Chronic kidney disease (CKD) affects individual welfare, healthcare systems and societal progress. Of the multifaceted etiological factors, type 1 diabetes mellitus (T1DM) is a prominent contributor to CKD.

Materials and methods: We analysed the global incidence, prevalence, deaths and disability-adjusted life-years (DALYs) with age-standardised rates of CKD due to T1DM (CKD-T1DM) in 2021, stratified by subtype. We calculated the temporal trends in the infirmity burden from 1990 to 2019 using a linear regression model. The age-period-cohort (APC) and Bayesian APC models predicted the prospective burden over the next 25 years. Sensitivity analysis was conducted using Autoregressive Integrated Moving Average and Exponential Smoothing models.

Results: Globally, there were 95 140 incidences, 6 295 711 prevalence cases, 94 020 deaths and 3 875 628 DALYs due to CKD-T1DM. Males and young-to-middle-aged individuals were more likely to be affected by CKD-T1DM. The middle-socio-demographic index regions were at higher risk. A considerable variation in disease burden was observed across the Global Burden of Disease super regions and countries. The number of patients with CKD-T1DM surged globally from 1990 to 2021. The projections indicated a continuous increase until 2046, driven by ageing populations and unmet therapeutic needs in low-resource settings.

Conclusions: CKD-T1DM poses a growing public health threat, necessitating region-specific strategies that address healthcare inequities, promote early screening and prioritise nephroprotective therapies among T1DM populations.

Aims: The ongoing FAMILIAR trial aims to provide evidence for clinical decision-making and offer a novel treatment paradigm in type 2 diabetes mellitus (T2DM) management. The interim findings of FAMILIAR through Week 24 are reported.

Materials and methods: FAMILIAR is a multicentre, randomised, double-blind study comparing the efficacy and safety of imeglimin versus placebo in adult Japanese patients with T2DM and inadequate glycaemic control despite dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, plus diet/exercise modifications. Patients entered a 24-week double-blind treatment phase (oral imeglimin 1000 mg or placebo twice daily) followed by an 80-week open-label phase (oral imeglimin 1000 mg twice daily). The primary end-point was change in glycated haemoglobin (HbA1c) level from baseline at Week 24. Safety was also monitored.

Results: Overall, 117 patients were randomised (imeglimin, n = 58; placebo, n = 54; excluded, n = 5). The least squares mean (standard error) changes in HbA1c level (baseline to Week 24) for the imeglimin and placebo groups, respectively, were -0.65% (0.11%) and 0.38% (0.11%) in the overall population (group-difference -1.02% [95% confidence interval -1.33%, -0.72%]; p < 0.001); -0.47% (0.17%) and 0.32% (0.18%) in patients aged <65 years (-0.79% [-1.29%, -0.29%]; p = 0.003); and -0.80% (0.14%) and 0.42% (0.14%) in patients aged ≥65 years (-1.22% [-1.61%, -0.82%]; p < 0.001). One patient in the imeglimin group had mild hypoglycaemia; the safety profile was favourable.

Conclusions: Imeglimin represents a potential new treatment option for patients with T2DM and inadequate glycaemic control with DPP-4 inhibitors, including those aged ≥65 years.

Clinical trial registration: jRCTs061210082.

Aims: To evaluate the efficacy and safety of siRNA drugs that lower Lp(a) in patients with dyslipidaemia.

Materials and methods: A network meta-analysis and systematic review were conducted to compare siRNA drugs targeting Lp(a), based on relevant randomized controlled trials (RCTs). A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library (up to October 24, 2024). RCTs with an intervention duration of at least 12 weeks were included. Eligible studies compared siRNA drugs that reduce Lp(a), including both Lp(a)-targeted and non-targeted agents, with placebo or other siRNA drugs that reduce Lp(a). The primary outcomes were the percentage reduction and absolute reduction in Lp(a), percentage reduction in low-density lipoprotein cholesterol (LDL-C), percentage reduction in apolipoprotein B (apo(B)), adverse events and serious adverse events, including injection-site reactions. The risk of bias was assessed using the Cochrane Risk of Bias Tool (ROB2), and a random-effects network meta-analysis was performed using the frequentist approach. Confidence in effect estimates was evaluated using the Confidence In Network Meta-Analysis (CINeMA) framework.

Results: A total of 14 trials involving 5646 participants were included. Lp(a)-targeted siRNA agents, particularly Olpasiran, demonstrated strong efficacy in significantly reducing Lp(a) levels, with the greatest percentage reduction in Lp(a) (mean difference [MD]: -92.06%; 95% CI: -102.43% to -81.69%; P-score: 0.98). Olpasiran also showed the greatest absolute reduction in Lp(a) (MD: -250.70 nmol/L; 95% confidence interval [CI]: -279.89 to -221.50; P-score: 0.99). Certain non-Lp(a)-targeted siRNA agents, such as inclisiran and zodasiran, also showed modest reductions in Lp(a) levels, reducing Lp(a) by approximately 15%. Lp(a)-targeted siRNA agents reduced LDL-C by more than 20% and decreased apo(B) by approximately 15%. In terms of safety, most drugs exhibited favourable safety profiles with no significant differences compared to placebo. However, zerlasiran raised concerns regarding injection-site reactions and other adverse events when compared to placebo.

Conclusions: Lp(a)-targeted siRNA agents have shown robust effectiveness in substantially reducing Lp(a) levels, including both percentage and absolute reductions, with moderate improvements in LDL-C and apo(B) concentrations. Non-Lp(a)-targeted siRNA agents also demonstrate modest reductions in Lp(a) levels. The safety profile is generally favourable, but zerlasiran and inclisiran may increase the incidence of injection-site reactions.