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Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial. 地中海饮食作为保护冠心病合并 2 型糖尿病和肥胖症患者肾功能的策略:CORDIOPREV 随机对照试验的二次分析。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-16 DOI: 10.1038/s41387-024-00285-3
Alicia Podadera-Herreros, Antonio P Arenas-de Larriva, Francisco M Gutierrez-Mariscal, Juan F Alcala-Diaz, Ana Ojeda-Rodriguez, Fernando Rodriguez-Cantalejo, Magdalena P Cardelo, Diego Rodriguez-Cano, Jose D Torres-Peña, Raul M Luque, Jose M Ordovas, Pablo Perez-Martinez, Javier Delgado-Lista, Jose Lopez-Miranda, Elena M Yubero-Serrano

Background: Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function.

Methods: 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention.

Results: Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024).

Conclusions: Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease.

Trial registration: URL, http://www.cordioprev.es/index.php/en .

Clinicaltrials: gov number, NCT00924937.

背景:2 型糖尿病(T2DM)被认为是慢性肾脏病(CKD)的独立危险因素。根据肥胖是否与 T2DM 同时存在,肥胖对减少肾功能障碍的治疗策略的确切贡献和不同反应仍有待全面阐明。我们的目标是进一步了解肥胖是如何影响 T2DM 和冠心病(CHD)患者的肾功能的,这些患者极易患上 CKD,从而确定最有效的饮食方法来保护肾功能。方法:1002 名患有冠心病且估计肾小球滤过率(eGFR)≥30 ml/min/1.73m2 的患者被随机分配到地中海饮食(35% 脂肪、22% MUFA、55% 碳水化合物)中。根据基线时是否患有 T2DM 和/或肥胖症,患者被分为四组:非肥胖/非 T2DM 组、肥胖/非 T2DM 组、非肥胖/T2DM 组和肥胖/T2DM 组。我们使用血清肌酐估算肾小球滤过率(eGFR)和尿白蛋白-肌酐比值(uACR)对饮食干预前和干预 5 年后的肾功能进行了评估:结果:与非糖尿病患者相比,肥胖症/T2DM 患者的基线 eGFR 最低,基线 uACR 最高(p 结论:肥胖症/T2DM 患者的基线 eGFR 最低,基线 uACR 最高:与非糖尿病患者相比,肥胖症对 T2DM 有叠加效应,导致肾功能下降比单纯 T2DM 更明显。对于同时患有 T2DM 和肥胖症并伴有更多代谢并发症的患者,就保护肾功能而言,食用地中海饮食似乎比低脂肪饮食更有益。这些发现为在心血管疾病二级预防中定制个性化的生活方式提供了宝贵的见解:URL, http://www.cordioprev.es/index.php/en .Clinicaltrials: gov number, NCT00924937.
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引用次数: 0
Risk factors for malnutrition in patients with diabetic foot ulcer and its association with prolonged length of hospitalization. 糖尿病足溃疡患者营养不良的风险因素及其与住院时间延长的关系。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-16 DOI: 10.1038/s41387-024-00290-6
Qian Ran, Weiwei Xu, Xili Zhao, Hang Sun, Li Liu, Yunqiu Luo

Purpose: The study was designed to investigate the occurrence and risk factors of malnutrition in diabetic foot ulcers (DFU) patients and examine the association between malnutrition and length of stay (LOS).

Methods: This observational study included DFU hospitalized patients in two campuses of a hospital from January 2021 to June 2023. The diagnosis standard of malnutrition was established by using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were followed up to ascertain the length of hospitalization, and hospital stays longer than 17 days were considered as prolonged LOS. To explore the risk factors of malnutrition and the association between malnutrition and LOS, univariate and multivariate logistic regression analyses were performed.

Results: Overall 219 DFU patients were enrolled, malnutrition was identified in 38.36% of patients according to GLIM criteria, and 92 patients (42%) were recognized as prolonged LOS. Logistic regression analyses showed that BMI (P <0.001), Alb (P = 0.002), HbA1c (P <0.001), ulcer infection (P <0.001), LOS (P = 0.010), and ABI (P = 0.024) were independent risk factors for malnutrition. Besides, malnutrition by GLIM criteria was closely related to prolonged LOS and malnourished DFU patients were 2.857 times (95% CI, 1.497-5.450; P = 0.001) likely to present prolonged LOS than that of normal nutrition.

Conclusion: Malnutrition was considered to be extremely prevalent in DFU patients and was associated with approximately three times higher likelihood of prolonged LOS. Implementing and disseminating the diagnostic criteria during routine practice is crucial, given the predictive efficacy of GLIM criteria.

目的:本研究旨在调查糖尿病足溃疡(DFU)患者营养不良的发生率和风险因素,并研究营养不良与住院时间(LOS)之间的关系:本观察性研究纳入了 2021 年 1 月至 2023 年 6 月期间某医院两个院区的糖尿病足溃疡住院患者。营养不良的诊断标准采用全球营养不良领导倡议(GLIM)标准。对患者进行随访以确定住院时间,住院时间超过17天的患者被视为长期住院患者。为了探究营养不良的风险因素以及营养不良与住院时间之间的关系,研究人员进行了单变量和多变量逻辑回归分析:共纳入 219 名 DFU 患者,根据 GLIM 标准,38.36% 的患者被确定为营养不良,92 名患者(42%)被认为延长了 LOS。逻辑回归分析表明,BMI(P 结论:营养不良被认为是极度营养不良:营养不良被认为在 DFU 患者中极为普遍,与延长 LOS 的可能性大约高出三倍有关。鉴于 GLIM 标准的预测效果,在常规实践中实施和推广诊断标准至关重要。
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引用次数: 0
The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review. 肠道微生物组操作对非酒精性脂肪肝患者血糖指数的影响:综述。
IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-05-10 DOI: 10.1038/s41387-024-00281-7
Azin Vakilpour, Ehsan Amini-Salehi, Arman Soltani Moghadam, Mohammad-Hossein Keivanlou, Negin Letafatkar, Arman Habibi, Mohammad Hashemi, Negar Eslami, Reza Zare, Naeim Norouzi, Hamed Delam, Farahnaz Joukar, Fariborz Mansour-Ghanaei, Soheil Hassanipour, Sandeep Samethadka Nayak

Background: Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action.

Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed.

Results: Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics.

Conclusion: Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.

背景:2 型糖尿病(T2DM)是非酒精性脂肪肝(NAFLD)的重要风险因素。非酒精性脂肪肝患者的空腹血糖(FBS)、空腹胰岛素(FI)和胰岛素抵抗(HOMA-IR)都会增加。使用益生菌、益生菌和合成益生菌调节肠道微生物已显示出治疗非酒精性脂肪肝的前景。这项荟萃研究旨在调查肠道微生物调节对非酒精性脂肪肝患者血糖指数的影响,并讨论潜在的作用机制:截至 2023 年 3 月,我们在 PubMed、Web of Science、Scopus 和 Cochrane 图书馆进行了系统检索,以了解评估益生菌、益生元和合成益生菌对非酒精性脂肪肝患者影响的荟萃分析。研究采用了随机效应模型、敏感性分析和亚组分析:肠道微生物疗法明显降低了 HOMA-IR(ES:-0.41;95%CI:-0.52,-0.31;P 结论:益生菌、益生元和增效益生菌对非酒精性脂肪肝患者的疗效非常明显:服用益生菌、益生元和合生元能明显降低 FI 和 HOMA-IR,但对 FBS 没有明显影响。
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引用次数: 0
Factors associated with body weight gain and insulin-resistance: a longitudinal study 体重增加和胰岛素抵抗的相关因素:一项纵向研究
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-22 DOI: 10.1038/s41387-024-00283-5
Carola Buscemi, Cristiana Randazzo, Anna Maria Barile, Simona Bo, Valentina Ponzo, Rosalia Caldarella, Alexis Elias Malavazos, Roberta Caruso, Piero Colombrita, Martina Lombardo, Silvio Buscemi

Background

Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight.

Subjects

A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally, PNPLA3 was genotyped.

Results

Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years, P < 0.001; body mass index, 27.8 ± 6.5 vs 28.1 ± 5.1 kg/m2, P = ns; body weight, 76.7 ± 22.1 vs 74.2 ± 14.7 kg, P = ns; final body weight, 86.3 ± 23.7 vs 72.9 ± 14.2 kg, P < 0.001) and diet characteristics, as well as insulin concentrations and HOMA-IR values, were similar in both groups. Four years later, G showed significantly increased EI, insulin concentrations, and HOMA-IR values. G had a higher prevalence of the PNPLA3 CG and GG alleles than NG (P < 0.05). The presence of G was independently associated with age (OR = 1.031), EI change (OR = 2.257), and unfavorable alleles of PNPLA3 gene (OR = 1.700). Final body mass index, waist circumference, and EI were independently associated with final HOMA-IR (P < 0.001).

Conclusions

EI is associated with body weight gain, and genetic factors may influence the energy balance. Insulin resistance is a consequence of weight gain, suggesting a possible intracellular protective mechanism against substrate overflow.

Clinical trial registration

ISRCTN15840340.

背景肥胖是能量摄入(EI)长期超过能量消耗的结果。然而,包括胰岛素抵抗在内的潜在代谢因素仍不清楚。这项研究对体重变化的相关因素进行了纵向调查。研究人员使用经过验证的当地居民食物频率问卷,对过去 12 个月中能量和宏量营养素的习惯性摄入量进行了评估。β细胞功能和胰岛素抵抗的静态模型评估(HOMA-IR)被用作胰岛素抵抗的替代测量指标。此外,还对 PNPLA3 进行了基因分型。初始人体测量(G vs. NG:年龄,44 ± 13 vs 51 ± 13 岁,P < 0.001;体重指数,27.8 ± 6.5 vs 28.1 ± 5.1 kg/m2,P = ns;体重,76.7 ± 22.1 vs 74.2 ± 14.7 kg,P = ns;最终体重,86.3 ± 23.7 vs 72.9 ± 14.2 kg,P < 0.001),两组的饮食特征以及胰岛素浓度和 HOMA-IR 值相似。四年后,G 组的 EI、胰岛素浓度和 HOMA-IR 值明显增加。G 组的 PNPLA3 CG 和 GG 等位基因发生率高于 NG 组(P < 0.05)。G 的存在与年龄(OR = 1.031)、EI 变化(OR = 2.257)和 PNPLA3 基因的不利等位基因(OR = 1.700)独立相关。最终体重指数、腰围和 EI 与最终 HOMA-IR 独立相关(P < 0.001)。胰岛素抵抗是体重增加的结果,这表明细胞内可能存在防止底物溢出的保护机制。
{"title":"Factors associated with body weight gain and insulin-resistance: a longitudinal study","authors":"Carola Buscemi, Cristiana Randazzo, Anna Maria Barile, Simona Bo, Valentina Ponzo, Rosalia Caldarella, Alexis Elias Malavazos, Roberta Caruso, Piero Colombrita, Martina Lombardo, Silvio Buscemi","doi":"10.1038/s41387-024-00283-5","DOIUrl":"https://doi.org/10.1038/s41387-024-00283-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Obesity is the result of energy intake (EI) chronically exceeding energy expenditure. However, the potential metabolic factors, including insulin resistance, remain unclear. This study longitudinally investigated factors associated with changes in body weight.</p><h3 data-test=\"abstract-sub-heading\">Subjects</h3><p>A cohort of 707 adults without diabetes were investigated at the 4-year follow-up visit. The habitual intake of energy and macronutrients during the past 12 months was assessed using a validated Food Frequency Questionnaire for the local population. Homeostatic model assessment of β-cell function and insulin resistance (HOMA-IR) was used as a surrogate measure of insulin resistance. Additionally, <i>PNPLA3</i> was genotyped.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Eighty-seven participants were weight gainers (G; cutoff value = 5 kg), and 620 were non-gainers (NG). Initial anthropometric (G vs. NG: age, 44 ± 13 vs 51 ± 13 years, <i>P</i> &lt; 0.001; body mass index, 27.8 ± 6.5 vs 28.1 ± 5.1 kg/m<sup>2</sup>, <i>P</i> = ns; body weight, 76.7 ± 22.1 vs 74.2 ± 14.7 kg, <i>P</i> = ns; final body weight, 86.3 ± 23.7 vs 72.9 ± 14.2 kg, <i>P</i> &lt; 0.001) and diet characteristics, as well as insulin concentrations and HOMA-IR values, were similar in both groups. Four years later, G showed significantly increased EI, insulin concentrations, and HOMA-IR values. G had a higher prevalence of the PNPLA3 CG and GG alleles than NG (<i>P</i> &lt; 0.05). The presence of G was independently associated with age (OR = 1.031), EI change (OR = 2.257), and unfavorable alleles of PNPLA3 gene (OR = 1.700). Final body mass index, waist circumference, and EI were independently associated with final HOMA-IR (<i>P</i> &lt; 0.001).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>EI is associated with body weight gain, and genetic factors may influence the energy balance. Insulin resistance is a consequence of weight gain, suggesting a possible intracellular protective mechanism against substrate overflow.</p><h3 data-test=\"abstract-sub-heading\">Clinical trial registration</h3><p>ISRCTN15840340.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634570","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}
引用次数: 0
Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials 叶酸补充剂对 2 型糖尿病患者炎症和同型半胱氨酸的影响:随机对照试验的系统回顾和荟萃分析
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-22 DOI: 10.1038/s41387-024-00282-6
Kabelo Mokgalaboni, Given. R. Mashaba, Wendy N. Phoswa, Sogolo. L. Lebelo

Background

The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM.

Methods

PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots.

Results

Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = −1.53, 95%CI (−2.14,−0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = −0.68, 95%CI (−1.34, −0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = −0.86, 95%CI (−2.65, 0.93), p = 0.34), and interleukin-6 (SMD = −0.04, 95%CI (−1.08, 1.01), p = 0.95) was observed.

Conclusion

Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.

背景在不同条件下观察到了叶酸的有益作用,但有关 2 型糖尿病(T2DM)患者炎症和减少心血管疾病(CVD)的现有证据有限。本研究旨在探讨叶酸对 T2DM 患者的炎症和同型半胱氨酸的影响。通过 Review Manager(5.4 版)和 metaHun 进行随机效应模型荟萃分析。结果分析了9项试验中426名T2DM患者的数据。与安慰剂相比,叶酸补充剂对同型半胱氨酸水平的影响较大,SMD = -1.53, 95%CI (-2.14,-0.93), p <0.05。此外,我们还观察到对 C 反应蛋白的中等边际效应(SMD = -0.68,95%CI (-1.34,-0.01),p = 0.05)。但对肿瘤坏死因子-α(SMD = -0.86,95%CI (-2.65,0.93),p = 0.34)和白细胞介素-6(SMD = -0.04,95%CI (-1.08,1.01),p = 0.95)没有观察到明显的影响。然而,叶酸对炎症的影响尚无定论。
{"title":"Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials","authors":"Kabelo Mokgalaboni, Given. R. Mashaba, Wendy N. Phoswa, Sogolo. L. Lebelo","doi":"10.1038/s41387-024-00282-6","DOIUrl":"https://doi.org/10.1038/s41387-024-00282-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = −1.53, 95%CI (−2.14,−0.93), <i>p</i> &lt; 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = −0.68, 95%CI (−1.34, −0.01), <i>p</i> = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = −0.86, 95%CI (−2.65, 0.93), <i>p</i> = 0.34), and interleukin-6 (SMD = −0.04, 95%CI (−1.08, 1.01), <i>p</i> = 0.95) was observed.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"136 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634552","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}
引用次数: 0
An algorithm for the use of anti-obesity medications 使用抗肥胖药物的算法
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-18 DOI: 10.1038/s41387-024-00278-2
Fereshteh Dehghani, Mitra Ali Ahmadi, Marleigh Hefner, Gaurav Kudchadkar, Wasiuddin Najam, Masoud Nateqi, Md Abu Bakkar Siddik, Holli Booe, Nikhil V. Dhurandhar
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引用次数: 0
Role of liver FGF21-KLB signaling in ketogenic diet-induced amelioration of hepatic steatosis 肝脏 FGF21-KLB 信号在生酮饮食诱导的肝脏脂肪变性改善中的作用
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-12 DOI: 10.1038/s41387-024-00277-3
Wanrong Guo, Huanyi Cao, Yunfeng Shen, Wuguo Li, Wei Wang, Lidan Cheng, Mengyin Cai, Fen Xu

Background

The effectiveness of ketogenic diet (KD) in ameliorating fatty liver has been established, although its mechanism is under investigation. Fibroblast growth factor 21 (FGF21) positively regulates obesity-associated metabolic disorders and is elevated by KD. FGF21 conventionally initiates its intracellular signaling via receptor β-klotho (KLB). However, the mechanistic role of FGF21-KLB signaling for KD-ameliorated fatty liver remains unknown. This study aimed to delineate the critical role of FGF21 signaling in the ameliorative effects of KD on hepatic steatosis.

Methods

Eight-week-old C57BL/6 J mice were fed a chow diet (CD), a high-fat diet (HFD), or a KD for 16 weeks. Adeno-associated virus-mediated liver-specific KLB knockdown mice and control mice were fed a KD for 16 weeks. Phenotypic assessments were conducted during and after the intervention. We investigated the mechanism underlying KD-alleviated hepatic steatosis using multi-omics and validated the expression of key genes.

Results

KD improved hepatic steatosis by upregulating fatty acid oxidation and downregulating lipogenesis. Transcriptional analysis revealed that KD dramatically activated FGF21 pathway, including KLB and fibroblast growth factor receptor 1 (FGFR1). Impairing liver FGF21 signaling via KLB knockdown diminished the beneficial effects of KD on ameliorating fatty liver, insulin resistance, and regulating lipid metabolism.

Conclusion

KD demonstrates beneficial effects on diet-induced metabolic disorders, particularly on hepatic steatosis. Liver FGF21-KLB signaling plays a critical role in the KD-induced amelioration of hepatic steatosis.

背景生酮饮食(KD)在改善脂肪肝方面的有效性已经确立,但其机制仍在研究之中。成纤维细胞生长因子 21(FGF21)对肥胖相关的代谢紊乱有积极的调节作用,并在生酮饮食中升高。FGF21通常通过受体β-klotho(KLB)启动细胞内信号传导。然而,FGF21-KLB 信号在 KD 改善脂肪肝中的机理作用仍然未知。本研究旨在阐明 FGF21 信号在 KD 改善肝脂肪变性中的关键作用。腺相关病毒介导的肝脏特异性 KLB 基因敲除小鼠和对照组小鼠喂食 KD 16 周。在干预期间和之后进行表型评估。我们利用多组学研究了 KD 缓解肝脂肪变性的机制,并验证了关键基因的表达。转录分析表明,KD能显著激活FGF21通路,包括KLB和成纤维细胞生长因子受体1(FGFR1)。通过KLB敲除损害肝脏FGF21信号传导,削弱了KD对改善脂肪肝、胰岛素抵抗和调节脂质代谢的有益作用。肝脏 FGF21-KLB 信号在 KD 诱导的肝脂肪变性的改善过程中起着关键作用。
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引用次数: 0
Role of dietary interventions on microvascular health in South-Asian Surinamese people with type 2 diabetes in the Netherlands: A randomized controlled trial 饮食干预对荷兰南亚苏里南 2 型糖尿病患者微血管健康的作用:随机对照试验
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-10 DOI: 10.1038/s41387-024-00275-5
Anouk I. M. van der Velden, Daphne H. T. IJpelaar, Prataap K. Chandie Shaw, Hanno Pijl, Hans Vink, Johan van der Vlag, Ton J. Rabelink, Bernard M. van den Berg

Background/objectives

We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (EndocalyxTM) could stabilize microvascular function in Surinamese South-Asian patients with type 2 diabetes (SA-T2DM) in the Netherlands, a patient population more prone to develop vascular complications.

Subjects/methods

A randomized, placebo controlled, 3-arm intervention study was conducted in 56 SA-T2DM patients between 18 and 75 years old, for 3 consecutive months, with one additional follow up measurement 3 months after the last intervention. Sublingual microcirculation was assessed with SDF-imaging coupled to the GlycoCheckTM software, detecting red blood cell velocity, capillary density, static and dynamic perfused boundary region (PBR), and the overall microvascular health score (MVHS). Linear mixed models and interaction analysis were used to investigate the effects the interventions had on microvascular function.

Results

Despite a temporal improvement in BMI and HbA1c after FMD the major treatment effect on microvascular health was worsening for RBC-velocity independent PBRdynamic, especially at follow-up. Glycocalyx supplementation, however, reduced urinary MCP-1 presence and improved both PBRdynamic and MVHSdynamic, which persisted at follow-up.

Conclusions

We showed that despite temporal beneficial changes in BMI and HbA1c after FMD, this intervention is not able to preserve microvascular endothelial health in Dutch South-Asian patients with T2DM. In contrast, glycocalyx mimetics preserves the microvascular endothelial health and reduces the inflammatory cytokine MCP-1.

Clinical study registration

NCT03889236.

背景/目的我们研究了饮食干预,即空腹模拟饮食(FMD,Prolon®)或糖萼模拟补充剂(EndocalyxTM)是否能稳定荷兰苏里南南亚 2 型糖尿病患者(SA-T2DM)的微血管功能,该患者群体更容易出现血管并发症。研究对象/方法对 56 名年龄在 18 岁至 75 岁之间的南亚籍 2 型糖尿病患者进行了一项随机、安慰剂对照、3 臂干预研究,研究时间为连续 3 个月,最后一次干预 3 个月后再进行一次随访测量。通过 SDF 成像和 GlycoCheckTM 软件对舌下微循环进行评估,检测红细胞速度、毛细血管密度、静态和动态灌注边界区域(PBR)以及微血管健康总体评分(MVHS)。结果尽管 FMD 后 BMI 和 HbA1c 在时间上有所改善,但治疗对微血管健康的主要影响是独立于 PBRdynamic 的红细胞速度恶化,尤其是在随访时。结论我们的研究表明,尽管 FMD 后 BMI 和 HbA1c 在时间上发生了有益的变化,但这种干预措施并不能保护荷兰南亚 T2DM 患者的微血管内皮健康。与此相反,糖萼模拟物能保护微血管内皮健康并降低炎性细胞因子 MCP-1。
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引用次数: 0
Usual intake of dairy products and the chance of pre-diabetes regression to normal glycemia or progression to type 2 diabetes: a 9-year follow-up 乳制品的通常摄入量与糖尿病前期血糖恢复正常或发展为 2 型糖尿病的几率:9 年跟踪调查
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-09 DOI: 10.1038/s41387-024-00257-7
Zahra Bahadoran, Parvin Mirmiran, Fereidoun Azizi

Background

We assessed the possible effect of usual dairy consumption on pre-diabetes (Pre-DM) remission or progression to type 2 diabetes (T2D).

Methods

Pre-DM adults (n = 334, mean age of 49.4 years, and 51.5% men) were assessed for dairy intakes (2006–2008) and followed up to 9 years for incidence of T2D or normal glycemia (NG). All biochemical measurements were done at baseline and all subsequent examinations with 3-y follow-up intervals. Multinomial regression models with adjustment of confounding variables were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) of incident T2D and NG for each serving/d dairy consumption.

Results

The odds of NG was significantly elevated by 69% (OR = 1.69, 95% CI = 1.00–2.86, P = 0.05) per 200 g/d increased high-fat dairy intake, while the amount of total dairy or low-fat dairy was not related to the outcomes. Higher intakes of yogurt were more likely to be associated with an increased odds of NG (OR = 1.82, 95% CI = 1.20–2.74, P = 0.01). Usual intakes of milk, cheese, or cream-butter were not associated to Pre-DM remission or progression to T2D.

Conclusion

Regular dairy consumption may increase the chance of Pre-DM regression to NG.

方法 对糖尿病前期成人(n = 334,平均年龄 49.4 岁,51.5% 为男性)的乳制品摄入量进行评估(2006-2008 年),并对糖尿病前期或血糖正常(NG)的发病率进行长达 9 年的随访。所有生化指标均在基线和所有后续检查中进行,随访间隔为 3 年。结果高脂乳制品摄入量每增加200克/天,NG发生几率显著增加69%(OR = 1.69,95% CI = 1.00-2.86,P = 0.05),而乳制品总量或低脂乳制品量与结果无关。酸奶摄入量越高,发生 NG 的几率越高(OR = 1.82,95% CI = 1.20-2.74,P = 0.01)。牛奶、奶酪或奶油黄油的通常摄入量与糖尿病前期缓解或发展为 T2D 无关。
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引用次数: 0
Association of food insecurity with changes in diet quality, weight, and glycemia over two years in adults with prediabetes and type 2 diabetes on medicaid 接受医疗补助的糖尿病前期和 2 型糖尿病成人两年内食物不安全与饮食质量、体重和血糖变化的关系
IF 6.1 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-04-09 DOI: 10.1038/s41387-024-00273-7
Kristine D. Gu, Jessica Cheng, Vicki Fung, Douglas E. Levy, Sydney McGovern, Jessica L. McCurley, Cheryl R. Clark, Anne N. Thorndike

Little is known about longitudinal associations between food insecurity (FI) and diet, weight, and glycemia in people with prediabetes and type 2 diabetes (T2D). In a secondary analysis of Medicaid-enrolled health center patients with prediabetes or T2D in Boston, Massachusetts (N = 188), we examined associations between food security (FS) and measures of diet quality, weight, and hyperglycemia. FS (10-item USDA FS module) was ascertained at baseline, 1-year, and 2-year follow-up and categorized as persistently secure, intermittently insecure, or persistently insecure. Associations between FS category and changes in Healthy Eating Index-2020 (HEI-20), body mass index (BMI), and hemoglobin A1c (A1c) from baseline to year 2 were assessed using multivariate generalized linear models. Participants had median (p25, p75) age of 52 (42, 57); 71.8% were female and 62.8% Hispanic. Over follow-up, 32.4% were persistently food secure, 33.0% intermittently insecure, and 34.5% persistently insecure. Baseline mean (SD) HEI-20, BMI, and A1c were 55.8 (14.5), 35.9 (8.7) kg/m2, 7.1% (1.6) and did not differ by FS category. FS category was not associated with changes in HEI-20, BMI, and A1c at 2 years (all p > 0.05). Results suggest that Medicaid-enrolled adults with prediabetes or T2D, regardless of FS status, would benefit from dietary and weight management interventions.

人们对食品不安全(FI)与糖尿病前期和 2 型糖尿病(T2D)患者的饮食、体重和血糖之间的纵向关系知之甚少。在对马萨诸塞州波士顿市医疗补助医疗中心的糖尿病前期或 T2D 患者(N = 188)进行的二次分析中,我们研究了食品安全(FS)与饮食质量、体重和高血糖之间的关系。在基线、1 年和 2 年的随访中确定了食品安全状况(美国农业部食品安全状况 10 项模块),并将其分为持续安全、间歇性不安全或持续不安全。使用多变量广义线性模型评估了FS类别与2020健康饮食指数(HEI-20)、体重指数(BMI)和血红蛋白A1c(A1c)从基线到第2年的变化之间的关系。参与者的中位(p25,p75)年龄为 52(42,57)岁;71.8% 为女性,62.8% 为西班牙裔。在随访过程中,32.4%的人持续有食物保障,33.0%的人间歇性无保障,34.5%的人持续无保障。基线平均(标清)HEI-20、BMI 和 A1c 分别为 55.8 (14.5)、35.9 (8.7) kg/m2、7.1% (1.6),且不因食物安全类别而异。FS 类别与 2 年后 HEI-20、BMI 和 A1c 的变化无关(所有 p > 0.05)。结果表明,参加医疗补助计划的成人糖尿病前期或 T2D 患者,无论其 FS 状况如何,都将受益于饮食和体重管理干预措施。
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引用次数: 0
期刊
Nutrition & Diabetes
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