Diabetes最新文献

{"title":"CRTC1 in Mc4r-expressing cells is required for peripheral metabolism and systemic energy homeostasis","authors":"Haruka Miyamori, Takumi Yokokawa, Motoki Miyakita, Kazuki Ozaki, Tsuyoshi Goto, Kazuo Inoue, Shigenobu Matsumura","doi":"10.2337/db24-0014","DOIUrl":"https://doi.org/10.2337/db24-0014","url":null,"abstract":"Melanocortin-4-receptor (Mc4r) is a G protein-coupled receptor (GPCR) that controls systemic energy balance by regulating food intake and energy expenditure. Although the detailed molecular mechanism remains unclear, the activation of cAMP signaling in Mc4r-expressing cells reportedly suppresses food intake and increases energy expenditure. cAMP-responsive element-binding protein-regulated transcriptional co-activator-1 (CRTC1) is selectively expressed in neuronal cells and participates in transcriptional control, thereby contributing to neuronal plasticity and energy homeostasis. Considering the cAMP-dependent regulation of CRTC1 activity, CRTC1 in Mc4r- expressing cells may contribute to energy balance regulation through the melanocortin pathway. In this context, we examined the physiological contribution of CRTC1 in Mc4r-expressing cells to energy metabolism. In this study, mice with CRTC1 deficiency in Mc4r-expressing cells exhibited 1) modest obesity, glucose intolerance, insulin resistance, hyperinsulinemia, and hyperlipidemia; 2) decreased systemic energy expenditure and thermogenesis; 3) suppression of melanocortin agonist-induced adaptation of energy expenditure and food intake; 4) impaired thermogenic programs and oxidative pathway in brown adipose tissue and skeletal muscle; and 5) enhanced lipogenic programs in the liver and white adipose tissue. These results provide novel insights into the molecular mechanisms underlying the regulation of energy balance by the melanocortin system.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People with Obesity and Type 2 Diabetes","authors":"Max C. Petersen, Mihoko Yoshino, Gordon I. Smith, Rafael C. Gaspar, Mario Kahn, Dmitri Samovski, Gerald I. Shulman, Samuel Klein","doi":"10.2337/db24-0083","DOIUrl":"https://doi.org/10.2337/db24-0083","url":null,"abstract":"Muscle sn-1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn-1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn-1,2-DAG and ceramide contents by using liquid chromatography-tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn-1,2-DAG and C18:0 ceramide contents after weight loss were not different than values before weight loss. In contrast, mitochondrial/ER C18:0 ceramide content decreased by ∼20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P<0.005). These results suggest a decrease in muscle mitochondrial/ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Single Dose of Phosphoinositide-3-kinase Inhibitor Alpelisib Induces Insulin Resistance in Healthy Adults: A Randomized Feasibility Study","authors":"Joshua R. Cook, Nur Bedeir, Zachary D. Sone, Julia Wattacheril, Henry N. Ginsberg, Blandine Laferrère","doi":"10.2337/db24-0402","DOIUrl":"https://doi.org/10.2337/db24-0402","url":null,"abstract":"Our objective is to test a single dose of the phosphoinositide-3-kinase (PI3K) inhibitor alpelisib as a tool for acute modeling of insulin resistance in healthy volunteers. This single-center, double-blind, phase 1 clinical trial randomized healthy adults to take a single oral dose of alpelisib 300 mg (n = 5) or placebo (n = 6) at bedtime, followed by measurement of glucose, insulin, and C-peptide levels after an overnight fast and during a 3-hour, 75-g oral glucose tolerance test. Fasting plasma glucose trended higher with alpelisib (mean ± S.D.: 93 ± 11 mg/dL) versus placebo (84 ± 5 mg/dL), while mean fasting serum insulin increased nearly fivefold (23 ± 12 µU/mL vs. 5 ± 3 µU/mL, respectively) and Homeostasis Model Assessment of Insulin Resistance scored 5.4 ± 3.1 for alpelisib and 1.1 ± 0.6 for placebo. During OGTT, incremental area under the curve (AUC) for insulin was over fourfold greater with alpelisib (22 ± 15 mU/mL x min) than placebo (5 ± 2 mU/mL x min); glucose AUC trended higher with alpelisib. Single-dose alpelisib was well tolerated and produced metabolic alterations consistent with acute induction of IR, validating its use for mechanistic study of insulin action in humans. (ClinicalTrials.gov registration: NCT05733455)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum. 189-OR: Food Insecurity and Inability to Obtain Recommended Medications, Diabetes Technology, and Multidisciplinary Services in Youth and Young Adults with Diabetes. Diabetes 2024;73 (Suppl. 1):189-OR","authors":"Angela D. Liese, Emmanuel F. Julceus, Caroline Rudisill, Faisal Malik, Kate Flory, Edward A. Frongillo, Katherine A. Sauder, Jason A. Mendoza","doi":"10.2337/db24-er12b","DOIUrl":"https://doi.org/10.2337/db24-er12b","url":null,"abstract":"In the abstract cited above, author Nadine El Kalach was inadvertently omitted from the author list. The full, correct author list is as follows: Nadine El Kalach, Emmanuel F. Julceus, Caroline Rudisill, Faisal Malik, Kate Flory, Edward A. Frongillo, Katherine A. Sauder, Jason A. Mendoza, and Angela D. Liese. All authors approve the addition and the order of the revised author list. The authors apologize for the omission. The online version of the abstract (https://doi.org/10.2337/db24-189-OR) has been updated to correct the error.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAS6 and AXL promote insulin resistance by rewiring insulin signaling and increasing insulin receptor trafficking to endosomes","authors":"Céline Schott, Amélie Germain, Julie Lacombe, Monica Pata, Denis Faubert, Jonathan Boulais, Peter Carmeliet, Jean-François Côté, Mathieu Ferron","doi":"10.2337/db23-0802","DOIUrl":"https://doi.org/10.2337/db23-0802","url":null,"abstract":"Growth-arrest specific 6 (GAS6) is a secreted protein that acts as a ligand for TAM receptors (TYRO3, AXL and MERTK). In humans, GAS6 circulating levels and genetic variations in GAS6 are associated with hyperglycemia and increased risk of type 2 diabetes. However, the mechanisms by which GAS6 influences glucose metabolism are not understood. Here, we show that Gas6 deficiency in mice increases insulin sensitivity and protects from diet-induced insulin resistance. Conversely, increasing GAS6 circulating levels is sufficient to reduce insulin sensitivity in vivo. GAS6 inhibits the activation of the insulin receptor (IR) and reduces insulin response in muscle cells in vitro and in vivo. Mechanistically, AXL and IR form a complex, while GAS6 reprograms signaling pathways downstream of IR. This results in increased IR endocytosis following insulin treatment. This study contributes to a better understanding of the cellular and molecular mechanisms by which GAS6 and AXL influence insulin sensitivity.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of BAF60b as a chromatin remodeling checkpoint of diet-induced fatty liver disease","authors":"Jing Zhong, Xiuyu Ji, Yali Zhao, Yihe Jia, Churui Song, Jinghuan Lv, Yuying Chen, Yanping Zhou, Xue Lv, Zhuoyin Yang, Zheyu Zhang, Qiyao Xu, Weihong Wang, Haiyan Chen, Aoyuan Cui, Yu Li, Zhuo-Xian Meng","doi":"10.2337/db24-0002","DOIUrl":"https://doi.org/10.2337/db24-0002","url":null,"abstract":"Overnutrition has gradually become the primary causative factor of nonalcoholic fatty liver disease (NAFLD). However, how nutritional signals are integrated to orchestrate the transcriptional programs important for NAFLD progression remains poorly understood. Here, we identified hepatic BAF60b as a lipid-sensitive subunit of the switch/sucrose-nonfermentable (SWI/SNF) chromatin-remodeling complex and is negatively associated with liver steatosis in mice and humans. Hepatic BAF60b deficiency promotes high-fat diet (HFD)-induced liver steatosis in mice, while transgenic expression of BAF60b in the liver attenuates HFD-induced obesity and NAFLD, both accompanied by a marked regulation of PPARγ expression. Mechanistically, through motif analysis of liver ATAC-Seq and multiple validation experiments, we identified CCAAT/enhancer-binding protein β (C/EBPβ) as the transcription factor that interacts with BAF60b to suppress PPARγ gene expression, thereby controlling hepatic lipid accumulation and NAFLD progression. This work uncovers hepatic BAF60b as a negative regulator of liver steatosis through C/EBPβ dependent chromatin remodeling.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1971-LB: Contributions of Fasting and Postprandial Glucose Increments to Overall Hyperglycemia in Pregnant Women with Type 1 Diabetes","authors":"PING LING, DAIZHI YANG, CHAOFAN WANG, XUEYING ZHENG, SIHUI LUO, XUBIN YANG, HONGRONG DENG, WEN XU, JINHUA YAN, JIANPING WENG","doi":"10.2337/db24-1971-lb","DOIUrl":"https://doi.org/10.2337/db24-1971-lb","url":null,"abstract":"Aims: To evaluate the relative contribution of fasting hyperglycemia (FHG) and postprandial hyperglycemia (PHG) to overall hyperglycemia across time in range (TIR) and glycated hemoglobin (HbA1c) categories in pregnant women with type 1 diabetes mellitus (T1DM). Materials and Methods: This observational study included 112 pregnant women with T1DM from the CARNATION study who wore continuous glucose monitoring (CGM) devices during pregnancy. The data from CGM were analyzed for TIR, AUC of PHG, AUC of FHG, FHG and PHG contribution rates. The levels of HbA1c (<6.0, 6.0-8.0, ≥8.0%) and TIR(<60, 60-78,≥78%) were categorized according to the guidelines, and the contribution of FHG and PHG to the overall hyperglycemia were compared. Results: A total of 295 CGM-HbA1c profiles were analyzed in this study. All women experienced a mean TIR of 75.6±19.0% and a mean HbA1c of 6.2±1.1% during pregnancy. The FHG contribution rates increased gradually with TIR decreasing [74.9(36.8, 100) vs. 69.1(13.4, 100) vs. 66.5 (10.0, 100), P<0.001] or with HbA1c increasing [57.8% (0, 100) vs. 72.7% (36.8, 100) vs. 80.7% (31.4, 100), P<0.001], whereas the contribution of PHG decreased progressively with diabetes worsening. Conclusions: FHG was the major contributor to hyperglycemia during pregnancy. Along with controlling the postprandial hyperglycemia, pregnant women with T1DM who did not reach the target of TIR or HbA1c may benefit more from the optimization of insulin regimens focusing on reducing the fasting hyperglycemia. Disclosure P. Ling: None. D. Yang: None. C. Wang: None. X. Zheng: None. S. Luo: None. X. Yang: None. H. Deng: None. W. Xu: None. J. Yan: None. J. Weng: None. Funding Science and Technology Planning Project of Guangzhou (grant/award number: 202102010154), Diabetes mellitus research fund program from Shanghai Medical and Health Development Foundation (grant/award number: DMRFP_II_14 from SHMHDF).","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1563-P: High Fat and Fructose Feeding Severely Impairs Hepatic Glucose Effectiveness but Not Insulin Action Under Euglycemic Conditions","authors":"DALE S. EDGERTON, GUILLAUME KRAFT, HANNAH L. WATERMAN, BEN FARMER, KALISHA YANKEY, MARTA S. SMITH, JON R. HASTINGS, MELANIE SCOTT, ALAN D. CHERRINGTON","doi":"10.2337/db24-1563-p","DOIUrl":"https://doi.org/10.2337/db24-1563-p","url":null,"abstract":"Diets high in fat and fructose (HFHF) disrupt glucose metabolism. This study compared the effects of a HFHF diet on liver insulin action vs glucose effectiveness. Dogs were fed either a chow or HFHF diet for 1 month. At the start of each study, 3-3H-glucose was infused and after a basal sampling period, somatostatin and basal glucagon were given. During the experimental period (4h) either insulin was infused into the hepatic portal vein at 4 fold basal, while glucose was delivered to maintain euglycemia (CHOW-INS and HFHF-INS), or glucose was infused to increase its level 2.5 fold, while insulin was maintained at basal (CHOW-GLC and HFHF-GLC) (n=6/grp). Plasma insulin, glucagon, glucose, and hepatic glucose load were matched within the respective groups. In response to selective hyperinsulinemia, net hepatic glucose balance (NHGB) was suppressed from output to uptake (basal period to last h; 1.2±0.1 to -1.0±0.2 vs 1.7±0.2 to 0.0±0.1; deltas of 2.2±0.2 vs 1.6±0.3 mg/kg/min in CHOW-INS vs HFHF-INS, respectively; p=0.2). Selective hyperglycemia, on the other hand, caused changes in NHGB of 1.1±0.2 to -2.5±0.4 vs 1.4±0.1 to 1.7±0.6; deltas of 3.6±0.4 vs -0.3±0.6 mg/kg/min in CHOW-GLC vs HFHF-GLC, respectively (p<0.001). Glucose turnover (Ra) was suppressed (basal period to last h) by 1.7±0.3 vs 1.3±0.1 mg/kg/min (p=0.4) in CHOW-INS vs HFHF-INS, and by 1.9±0.2 vs 0.5±0.1 mg/kg/min (p<0.001) in CHOW-GLC vs HFHF-GLC, respectively. Thus, the HFHF diet had a small, non-significant effect on liver insulin action under euglycemic conditions, whereas it severely impaired the effect of hyperglycemia in the presence of basal insulin (i.e. hepatic glucose effectiveness). These data demonstrate that the “gold standard” hyperinsulinemic euglycemic clamp may overlook substantial diet induced liver dysfunction. Furthermore, Ra accounts for glucose production but not liver uptake, thus has the potential to miss critical and substantial changes in liver glucose metabolism. Disclosure D.S. Edgerton: None. G. Kraft: None. H.L. Waterman: None. B. Farmer: None. K. Yankey: None. M.S. Smith: None. J.R. Hastings: None. M. Scott: None. A.D. Cherrington: Consultant; Abvance Therapeutics. Research Support; Abvance Therapeutics. Advisory Panel; AdipoPharma. Research Support; Cellular Longevity, Inc. dba Loyal. Advisory Panel; Fractyl Health, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Consultant; Paratus, Portal Insulin. Advisory Panel; Sekkei Bio, Sensulin Labs, LLC. Consultant; Thetis Pharmaceuticals, LLC. Funding R01DK18243","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"138-OR: Pioglitazone Amplifies the Decrease in HbA1c and Prevents the Increase in Plasma Ketone Caused by Dapagliflozin in Type 1 Diabetes Mellitus Patients","authors":"MUHAMMAD ABDUL-GHANI, GOZDE BASKOY, AFIF NAKHLEH, SIHAM ABDELGANI, FAHD AL-MULLA, MOHAMED ABU-FARHA, FAHAD ALAJMI, THAMER ALESSA, RALPH A. DEFRONZO, NAIM SHEHADEH","doi":"10.2337/db24-138-or","DOIUrl":"https://doi.org/10.2337/db24-138-or","url":null,"abstract":"Introduction and Objectives: SGLT2 inhibitors (SGLT2i) lower the plasma glucose concentration in T1DM patients. However, they cause an increase in plasma ketone concentration and risk of ketoacidosis. The aim of the present study is to examine whether pioglitazone amplifies the decrease in HbA1c and prevents the increase in plasma ketone concentration caused by dapagliflozin in T1DM patients. Methods: After a 4-week run in period, 60 T1DM patients received dapagliflozin 10 mg for 12 weeks. At week 16 patients were randomized to receive in double blind fashion pioglitazone (45 mg) or matching placebo for an additional 16 weeks. Results: T1DM patients were 42±3 years of age, 30% female, BMI=26.8±0.7, HbA1c=8.5±0.2%, insulin dose= 63±4 units, and eGFR=114±6 ml/min. Dapagliflozin caused -0.63±0.18%, and -0.56±0.11% decrease from baseline in HbA1c at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.001). At week 32, the decrease from baseline in HbA1c was -0.86±0.3 and -0.44±0.17 in subjects receiving pioglitazone and placebo, respectively. Thus, the HbA1c was -0.42±0.12 lower in subjects receiving pioglitazone versus placebo (p<0.05). Plasma ketone concentration increased above baseline by 0.12±0.03 mM and 0.14±0.03 mM at week 16 in subjects receiving pioglitazone and placebo, respectively (both p<0.05). At week 32 plasma ketone concentration remained elevated above baseline in subjects receiving placebo (0.15±0.03 mM, p<0.05), and decreased below baseline (-0.06±0.02mM, p<0.05) in subjects receiving pioglitazone. Thus, the difference in plasma ketone concentration between subjects receiving pioglitazone and placebo at week 32 was -0.19±0.3, p<0.001. Conclusion: Addition of pioglitazone to SGLT2i in T1DM patients amplifies the decrease in HbA1c and prevents the increase in plasma ketone caused by SGLT2i, allowing long-term cardiovascular and renal outcome studies to be carried out safely in T1DM patients. Disclosure M. Abdul-Ghani: None. G. Baskoy: None. A. Nakhleh: None. S. Abdelgani: None. F. Al-Mulla: None. M. Abu-farha: None. F. Alajmi: Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. T. Alessa: None. R.A. DeFronzo: Advisory Panel; AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Intarcia Therapeutics, Inc., Aardvark, Renalytix, Corcept Therapeutics, Alnylam Pharmaceuticals, Inc. Research Support; Boehringer-Ingelheim, AstraZeneca, 89bio, Inc., Amgen Inc., Medality, Corcept Therapeutics. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Renalytix. N. Shehadeh: Research Support; Abbott. Advisory Panel; AstraZeneca, Eli Lilly and Company, Boehringer-Ingelheim. Research Support; Novo Nordisk Foundation. Funding The study was funded by JDRF grant to MAG. Astrazeneca provided dapagliflozin.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1666-P: Effect of Obesity in Family History (FH) on the Prevalence of Type 2 Diabetes Mellitus (T2DM), Hypertension (HT), and Dyslipidemia (DL)","authors":"IZUMI IKEDA, KAZUYA FUJIHARA, YASUNAGA TAKEDA, CHIKA HORIKAWA, SATORU KODAMA, EFREM D. FERREIRA, YASUMICHI MORI, TAKASHI KADOWAKI, RITSUKO YAMAMOTO-HONDA, YASUJI ARASE, HIROHITO SONE","doi":"10.2337/db24-1666-p","DOIUrl":"https://doi.org/10.2337/db24-1666-p","url":null,"abstract":"Heritability and obesity are strongly associated with the prevalence of T2DM, HT, and DL. We compared the effects of an FH of T2DM, HT, and DL combined with obesity on the prevalence of each in the same population. Of 41931 participants who underwent health checkups, the effects of an FH and BMI on the prevalence of those conditions were analyzed cross-sectionally. Prevalences of T2DM, HT, and DL were 5%, 20%, and 48%, respectively. Logistic regression analysis showed that ORs increased for all three as the number of FH positive cases increased and was most pronounced for T2DM. An FH of obesity and increased BMI were additively associated with the prevalence of the three diseases compared to BMI 20.0-21.9 and no positive FH (Fig. A). In addition, the combination of the number of family members with FH positivity (0,1, 2, ≥3) and obesity was additively associated with an increased FH of the three diseases compared to non-obesity and no FH of any of these diseases (Fig. B). For T2DM, the OR increased sharply in non-obese participants when the number of those with an FH of T2DM was ≥3 (14.4 [8.88-23.5]), but in obese participants the OR increased sharply when the number of those with an FH of T2DM was 2 (12.2 [8.85-16.9]) (Fig. B). Results suggest that, especially for T2DM, avoidance of obesity may be effective in reducing the prevalence of these disorders in those with many FH-positive family members. Disclosure I. Ikeda: None. K. Fujihara: None. Y. Takeda: None. C. Horikawa: None. S. Kodama: None. E.D. Ferreira: None. Y. Mori: None. T. Kadowaki: None. R. Yamamoto-Honda: None. Y. Arase: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}