Diabetes, Obesity & Metabolism最新文献

{"title":"Evaluation of the efficacy and safety of controlled-release phentermine/topiramate in adults with obesity in Korea: A randomized, double-blind, placebo-controlled, phase 4 trial (QUEEN's study).","authors":"Sangmo Hong, Won Jun Kim, Eun Seok Kang, In-Kyung Jeong, Chong Hwa Kim, Ki Young Lee, Sungrae Kim, Seung Joon Oh, Chang Beom Lee","doi":"10.1111/dom.16119","DOIUrl":"https://doi.org/10.1111/dom.16119","url":null,"abstract":"<p><strong>Aims: </strong>This study evaluated the efficacy and safety of a combination of phentermine and delayed-release topiramate (PHEN/TPM CR) versus placebo as an adjunct to standard lifestyle recommendations in Korean adults.</p><p><strong>Materials and methods: </strong>This 56-week, randomized, double-blind, placebo-controlled, phase 4 trial enrolled adults (age 19-70 years) with obesity (BMI ≥ 25 kg/m²) at eight sites in South Korea. After a 12-week lifestyle programme, participants were randomly assigned in a 1:1 ratio to receive PHEN/TPM CR or placebo. PHEN/TPM CR was commenced at 3.75 mg/23 mg daily for 14 days and increased to 7.5 mg/46 mg daily, and to 15 mg/92 mg if 3% weight loss was not achieved after 12 weeks. The primary outcomes were percentage change in body weight from baseline to Week 56.</p><p><strong>Results: </strong>A total of 232 participants underwent randomization. At 56 weeks, the percentage change in body weight was -8.3% with PHEN/TPM CR and -2.3% with placebo (treatment difference -6.1%; 95% confidence interval [CI], -7.7 to -4.5, p < 0.001). Participants receiving PHEN/TPM CR were more likely to achieve ≥5% weight loss compared with those receiving placebo (68.5% vs. 25.0%, odds ratio [OR], 6.4; 95% CI, 3.5 to 11.6; p < 0.001). Dizziness, paraesthesia and dry mouth were more common in the PHEN/TPM CR group, although most adverse events were mild or moderate.</p><p><strong>Conclusions: </strong>Administration of PHEN/TPM CR plus lifestyle intervention in Korean adults with obesity resulted in a greater reduction in body weight and adiposity than lifestyle intervention alone.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp in a real-world setting in China.","authors":"Lixin Guo, Liming Chen, Fan Zhao, Xiaoyun Liu, Hongcheng Ding, Kun Wang, Xing Zhong, Vinay Babu Shankarappa, Gaurav Chaudhary","doi":"10.1111/dom.16139","DOIUrl":"https://doi.org/10.1111/dom.16139","url":null,"abstract":"<p><strong>Aims: </strong>To investigate glycaemic control in Chinese adults with type 2 diabetes (T2D) initiating, or switching to insulin degludec/insulin aspart (IDegAsp), a co-formulation of basal, and bolus insulin, in a real-world setting.</p><p><strong>Materials and methods: </strong>A 20-week, prospective, single-arm, open-label, non-interventional study was conducted in Chinese adults with T2D initiating, or switching to IDegAsp after anti-hyperglycaemic treatment with oral antidiabetic drugs (OADs), other insulins, or glucagon-like peptide-1 receptor agonists. The primary endpoint was a change in HbA_1c from baseline to end of the study; the secondary endpoints included a change in fasting plasma glucose and Diabetes Treatment Satisfaction Questionnaire (DTSQ) score.</p><p><strong>Results: </strong>Significant reductions were observed in mean HbA_1c and fasting plasma glucose, among both the overall population (N = 878; -1.27%-points [95% CI: -1.36; -1.19]; p < 0.0001, and -1.61 mmol/L [95% CI: -1.81; -1.41]; p < 0.0001, respectively), and in subgroups switching from OADs only, or basal, or premix insulins ± OADs. The mean total DTSQ score increased from 26.4 (baseline) to 31.6 (end-of-study). No significant, or unexpected tolerability, or safety issues were observed. Significant reductions were observed in incidence rates of non-severe (rate ratio 0.37 [95% CI: 0.24; 0.59]; p < 0.0001) and nocturnal non-severe (rate ratio 0.45 [95% CI: 0.21; 0.94]; p = 0.0326) hypoglycaemic episodes.</p><p><strong>Conclusions: </strong>In a broad, real-world Chinese population of adults with T2D, initiating or switching to IDegAsp was associated with improved glycaemic control and lower rates of hypoglycaemia. The use of IDegAsp could be an effective treatment option for those with suboptimal glycaemic control or therapeutic inertia.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the common genetic architecture and causality of metabolic disorders with neurodegenerative diseases.","authors":"Hao Hong, Qi Fu, Pan Gu, Jingyi Zhao, Jinglan Dai, Kuanfeng Xu, Tao Yang, Hao Dai, Sipeng Shen","doi":"10.1111/dom.16130","DOIUrl":"https://doi.org/10.1111/dom.16130","url":null,"abstract":"<p><strong>Background: </strong>The co-occurrence of metabolic dysfunction and neurodegenerative diseases suggests a genetic link, yet the shared genetic architecture and causality remain unclear. We aimed to comprehensively characterise these genetic relationships.</p><p><strong>Methods: </strong>We investigated genetic correlations among four neurodegenerative diseases and seven metabolic dysfunctions, followed by bidirectional Mendelian randomisation (MR) to assess potential causal relationships. Pleiotropy analysis (PLACO) was used to detect the pleiotropic effects of genetic variants. Significant pleiotropic loci were refined and annotated using functional mapping and annotation (FUMA) and Bayesian colocalisation analysis. We further explored mapped genes with tissue-specific expression and gene set enrichment analyses.</p><p><strong>Results: </strong>We identified significant genetic correlations in nine out of 28 trait pairs. MR suggested causal relationships between specific trait pairs. Pleiotropy analysis revealed 25 931 significant single-nucleotide polymorphisms, with 246 pleiotropic loci identified via FUMA and 55 causal loci through Bayesian colocalisation. These loci are involved in neurotransmitter transport and immune response mechanisms, notably the missense variant rs41286192 in SLC18B1. The tissue-specific analysis highlighted the pancreas, left ventricle, amygdala, and liver as critical organs in disease progression. Drug target analysis linked 74 unique genes to existing therapeutic agents, while gene set enrichment identified 189 pathways related to lipid metabolism, cell differentiation and immune responses.</p><p><strong>Conclusion: </strong>Our findings reveal a shared genetic basis, pleiotropic loci, and potential causal relationships between metabolic dysfunction and neurodegenerative diseases. These insights highlight the biological connections underlying their phenotypic association and offer implications for future research to reduce the risk of neurodegenerative diseases.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When can weekly anti-obesity peptides be used for monthly administration?","authors":"Daniel V Santi","doi":"10.1111/dom.16134","DOIUrl":"https://doi.org/10.1111/dom.16134","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of Agile-4 score for liver cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease. A systematic review and meta-analysis of diagnostic test accuracy studies.","authors":"Konstantinos Malandris, Anastasia Katsoula, Aris Liakos, Thomas Karagiannis, Emmanouil Sinakos, Olga Giouleme, Philippos Klonizakis, Eleni Theocharidou, Eleni Gigi, Eleni Bekiari, Apostolos Tsapas","doi":"10.1111/dom.16142","DOIUrl":"https://doi.org/10.1111/dom.16142","url":null,"abstract":"<p><strong>Aims: </strong>A novel noninvasive score, Agile-4 score, combining liver stiffness measurements, aspartate aminotransferase/alanine aminotransferase, platelet count, diabetes status and sex has been developed for the identification of cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed the performance of Agile-4 for ruling-in/out liver cirrhosis in MASLD patients.</p><p><strong>Materials and methods: </strong>We searched Medline, Cochrane library, Web of science, Scopus and Echosens website up to May 2024. Eligible studies assessed the accuracy of Agile-4 for ruling-in (≥0.565) and ruling-out (<0.251) liver cirrhosis, using biopsy as the reference standard, at predefined thresholds. We calculated pooled sensitivity and specificity estimates for both Agile-4 thresholds alongside 95% confidence intervals following bivariate random-effect models. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2 tool.</p><p><strong>Results: </strong>We included seven studies with 6037 participants. An Agile-4 score ≥0.565 yielded a pooled specificity of 0.93 (95% CI, 0.86-0.97). Similarly, an Agile-4 score <0.251 excluded cirrhosis with a summary sensitivity of 0.90 (0.80-0.95). Assuming a cirrhosis prevalence of 30%, the positive predictive value (PPV) for ruling-in cirrhosis was 80%, while the negative predictive value for ruling-out cirrhosis was 95%. Most studies were at high or unclear risk for bias due to concerns regarding patient selection and the blinding status of Agile-4 score interpretation in relation to biopsy results.</p><p><strong>Conclusions: </strong>Agile-4 score performs well for ruling-in/out liver cirrhosis in MASLD patients. Owing to the relatively low PPV, sequential application of the Agile-4 after fibrosis-4 index (FIB-4) testing might further enhance its performance.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of choline alfoscerate on cognitive function and quality of life in type 2 diabetes: A double-blind, randomized, placebo-controlled trial.","authors":"Minji Sohn, Young Ho Park, Soo Lim","doi":"10.1111/dom.16131","DOIUrl":"https://doi.org/10.1111/dom.16131","url":null,"abstract":"<p><strong>Aims: </strong>This study evaluated the effects of choline alfoscerate on cognitive function and quality of life in T2DM patients with mild cognitive decrements.</p><p><strong>Materials and methods: </strong>In a double-blind, randomized, placebo-controlled trial, we recruited 36 individuals with T2DM and mild cognitive impairment which was assessed by the Mini-Mental State Examination (MMSE) score of 25-28, and randomly assigned them to receive either 1200 mg/day of choline alfoscerate or a placebo. Four additional questionnaires-the 36-Item Short Form Survey, the modified Informant Questionnaire on Cognitive Decline in the Elderly, the Korean version of Activities of Daily Living, and the Patient Health Questionnaire-were investigated at 6 and 12 months and analysed via mixed-effects models for repeated measures.</p><p><strong>Results: </strong>The mean age of study participants was 71.8 ± 5.3 years and 69.4% women. Six-month treatment with choline alfoscerate resulted in a non-significant increase in the MMSE score from 26.2 ± 1.3 to 26.9 ± 2.0, whereas the placebo group showed a non-significant decline from 26.6 ± 1.3 to 25.9 ± 2.3, resulting in a mean difference of +1.4 between the two groups (p = 0.059). At 12 months, the mean difference increased to +1.7 with statistical significance (p < 0.001). Physical health, as measured by the SF-36 survey, was significantly better in the choline alfoscerate group than in the placebo group.</p><p><strong>Conclusions: </strong>Choline alfoscerate 1200 mg once daily treatment showed marginal improvement in cognitive function in T2DM patients with mild cognitive impairment at 6 months but leading to significance at 12 months compared to placebo, suggesting its potential as an adjunct therapy for managing early cognitive decline.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of switching to insulin glargine 300 U/mL in people with type 2 diabetes uncontrolled on basal insulin in China: A post hoc subpopulation analysis of the INITIATION study.","authors":"Liming Chen, Hailong Wan, Jie Han, Caixian Yang, Hailin Shao, Jialin Li, Wensheng Yan, Jianzhong Xiao, Yadong Sun, Min Li, Yanfang Han, Lei Kang, Minlu Zhang","doi":"10.1111/dom.16144","DOIUrl":"https://doi.org/10.1111/dom.16144","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) in people with uncontrolled type 2 diabetes (T2D) switching from another basal insulin (BI).</p><p><strong>Materials and methods: </strong>INITIATION was an interventional, single-arm, phase IV study conducted in China. In this post hoc subpopulation analysis, the efficacy and safety of switching to Gla-300 was investigated in individuals with uncontrolled T2D (HbA1c 7.5%-11.0% [58-97 mmol/mol]) with previous BI. The primary endpoint was HbA1c change at week 24. Other measures of glycaemia, hypoglycaemia, insulin dose and weight change were assessed.</p><p><strong>Results: </strong>Three hundred and two participants switched to Gla-300 from another BI, including 232 from insulin glargine 100 U/mL (Gla-100) and 55 from insulin degludec (IDeg). At week 24, the mean ± standard error (SE) HbA1c change from baseline was -0.87% ± 0.06% (-9.5 ± 0.7 mmol/mol; p <0.001). Significant reductions in fasting plasma glucose (least-squares mean [LSM] change -1.13 mmol/L) and fasting self-measured blood glucose (LSM change -1.36 mmol/L) were also observed (both p <0.001). The mean daily BI dose increased from 18.86 U (0.27 U/kg) at baseline to 28.83 U (0.41 U/kg) at week 24. During the 24-week treatment period, the incidence of any hypoglycaemia was 43.8% for all hypoglycaemia and 15.1% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.7%). Minimal body weight change was documented.</p><p><strong>Conclusions: </strong>Gla-300 improved glycaemic control with a relatively low hypoglycaemia risk and minimal weight gain in Chinese people with T2D uncontrolled on previous BI.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of weight change on kidney transplantation outcomes: A systematic review and meta-analysis.","authors":"Mehmet Kanbay, Dimitrie Siriopol, Sama Mahmoud Abdel-Rahman, Zeynep Y Yilmaz, Lasin Ozbek, Mustafa Guldan, Sidar Copur, Katherine R Tuttle","doi":"10.1111/dom.16135","DOIUrl":"https://doi.org/10.1111/dom.16135","url":null,"abstract":"<p><strong>Background and aim: </strong>Kidney transplant recipients frequently experience a wide range of metabolic complications, including weight changes, which significantly impact patient outcomes and graft function, yet the relationship between weight gain and transplant outcomes remains poorly understood. This systematic review and meta-analysis aimed to synthesise existing evidence on the influence of weight gain on patient and graft outcomes following kidney transplantation to enhance clinical practice and optimise post-transplant care strategies.</p><p><strong>Materials and methods: </strong>A literature search was conducted across databases such as PubMed and Scopus for peer-reviewed studies published up to 8 August 2024. We included adult kidney transplant recipients (ages 18 years and older) with substantial and clinically relevant post-transplant weight gain and a control group without such changes, focusing on outcomes including all-cause mortality, graft survival, cardiovascular events and acute rejection.</p><p><strong>Results: </strong>The pooled analysis, which included data from 11 studies, indicated no significant association between post-transplant weight gain and the risk of all-cause mortality (hazard ratio [HR] 1.21, 95% confidence interval [CI] 0.69 to 2.10, p = 0.51; I² = 28%), cardiovascular events (HR 0.93, 95% CI 0.43 to 2.01, p = 0.85; I² = 32%) or acute rejection (HR 1.13, 95% CI 0.76 to 1.68, p = 0.55; I² = 9%). However, weight gain was significantly associated with an increased risk of graft failure (HR 1.58, 95% CI 1.22 to 2.05, p < 0.001; I² = 0%).</p><p><strong>Conclusion: </strong>Substantial and clinically relevant weight gain after kidney transplant was associated with a higher risk of graft failure. Within the timeframes of study observation, risks of all-cause mortality, cardiovascular events or acute rejection were not increased by weight gain in kidney transplant recipients.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of sodium-glucose cotransporter-2 inhibitors in myocardial infarction patients: A systematic review and meta-analysis.","authors":"Qiufeng Jia, Ankai Zuo, Hui Song, Chengrui Zhang, Xiangrui Fu, Keqing Hu, Fengshuang An","doi":"10.1111/dom.16122","DOIUrl":"https://doi.org/10.1111/dom.16122","url":null,"abstract":"<p><strong>Aims: </strong>Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to improve cardiovascular outcomes in individuals with heart failure (HF), type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, their efficacy following myocardial infarction (MI) remains unclear.</p><p><strong>Materials and methods: </strong>A systematic search was conducted using PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov. Primary outcomes included hospitalization for heart failure (HHF), cardiovascular (CV) death, a composite of HHF or CV death, all-cause death, major cardiovascular events (MACE), recurrent MI, severe arrhythmia, renal injury and stroke. Secondary outcomes targeted improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV).</p><p><strong>Results: </strong>Thirteen studies comprising 22 370 patients were included. Meta-analysis revealed that SGLT2 inhibitors reduced HHF (RR 0.69, 95% CI 0.61 to 0.78, p < 0.001), combined HHF or CV death (RR 0.87, 95% CI 0.77 to 0.99, p = 0.028), all-cause mortality (RR 0.82, 95% CI 0.73 to 0.93, p = 0.002), MACE (RR 0.68, 95% CI 0.53 to 0.88, p = 0.004), recurrent MI (RR 0.81, 95% CI 0.69 to 0.94, p = 0.007), severe arrhythmia (RR 0.54, 95% CI 0.34 to 0.85, p = 0.009) and renal injury (RR 0.68, 95% CI 0.53 to 0.87, p = 0.002). Improvement in LVEF (MD 3.96%, 95% CI 2.52 to 5.40; p < 0.001) and LVEDV (MD -5.52 mL, 95% CI -10.21 to -0.83; p = 0.021) was notably greater in the SGLT2 inhibitors group.</p><p><strong>Conclusions: </strong>In post-MI patients, we first found that SGLT2 inhibitors significantly lowered the risk of HHF, combined CV death or HHF, all-cause death, MACE, recurrent MI, severe arrhythmias and renal injury. Additionally, SGLT2 inhibitors improved LVEF and LVEDV.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes genetic risk and incident diabetes across diabetes risk enhancers.","authors":"Filipe A Moura, Frederick K Kamanu, Stephen D Wiviott, Robert P Giugliano, Miriam S Udler, Jose C Florez, Patrick T Ellinor, Marc S Sabatine, Christian T Ruff, Nicholas A Marston","doi":"10.1111/dom.16123","DOIUrl":"https://doi.org/10.1111/dom.16123","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the predictive value of a contemporary type 2 diabetes (T2D) polygenic score (PGS) in detecting incident diabetes across a range of diabetes risk factors.</p><p><strong>Materials and methods: </strong>We analysed participants in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial (ClinicalTrials.gov, number NCT0176463), which compared the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab versus placebo in lowering cardiovascular outcomes in participants with stable atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL (1.8 mmol/L) or higher who were receiving statin therapy. Genetic risk was characterized using a previously validated T2D PGS based on ~1.2 million single-nucleotide polymorphisms. PGS was analysed continuously and categorically as high (top 20% of the PGS) and low to intermediate (lower 80% of the PGS). The effect of evolocumab on incident diabetes in patients without diabetes at baseline was also assessed. HbA1c was measured at baseline and every 24 weeks thereafter, while FPG was measured at baseline, week 12, week 24 and every 24 weeks thereafter. Potential cases of incident diabetes were adjudicated centrally. Hazards ratios (HRs) for incident diabetes were adjusted for baseline characteristics and ancestry.</p><p><strong>Results: </strong>Among 9388 participants, the mean age was 63 ± 9 years and 22.7% were women, with median HbA1c 39 mmol/mol (36 mmol/mol - 41 mmol/mol; 5.7% [5.4%-5.9%]) and mean body mass index (BMI) 28.7 ± 5 kg/m². Diabetes developed in 690 participants (7.3%) during 2.3 years of median follow-up. T2D PGS predicted incident T2D (HR per 1-SD 1.22, 95% CI 1.14-1.32, p < 0.001). The rates of incident T2D in the high and low to intermediate genetic risk categories were 12.1% versus 6.8%, respectively (HR 1.43 95% CI 1.20-1.70, p < 0.001). Notably, high T2D genetic risk had greater predictive strength among individuals with lower HbA1c (P-int = 0.0499) and lower BMI (P-int = 0.004).</p><p><strong>Conclusions: </strong>The T2D polygenic score serves as an independent predictor of incident diabetes, particularly among individuals with lower distribution of traditional risk factors.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}