Diabetes & Metabolism Journal

Review

Pathophysiology
Epicardial Adipose Tissue and Heart Failure, Friend or Foe?: Dong-Hyuk Cho, Seong-Mi Park; Received June 20, 2023 Accepted December 11, 2023 Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0190 [Epub ahead of print]

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Heart failure (HF) management guidelines recommend individualized assessments based on HF phenotypes. Adiposity is a known risk factor for HF. Recently, there has been an increased interest in organ-specific adiposity, specifically the role of the epicardial adipose tissue (EAT), in HF risk. EAT is easily assessable through various imaging modalities and is anatomically and functionally connected to the myocardium. In pathological conditions, EAT secretes inflammatory cytokines, releases excessive fatty acids, and increases mechanical load on the myocardium, resulting in myocardial remodeling. EAT plays a pathophysiological role in characterizing both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). In HFrEF, EAT volume is reduced, reflecting an impaired metabolic reservoir, whereas in HFpEF, the amount of EAT is associated with worse biomarker and hemodynamic profiles, indicating increased EAT activity. Studies have examined the possibility of therapeutically targeting EAT, and recent studies using sodium glucose cotransporter 2 inhibitors have shown potential in reducing EAT volume. However, further research is required to determine the clinical implications of reducing EAT activity in patients with HF.

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New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza, Douglas Greig
International Journal of Molecular Sciences.2024; 25(8): 4407. CrossRef

Original Articles

Drug/Regimen
Effect of Lactobacillus plantarum LMT1-48 on Body Fat in Overweight Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial: Minji Sohn, Hyeyoung Jung, Woo Shun Lee, Tai Hoon Kim, Soo Lim; Diabetes Metab J. 2023;47(1):92-103. Published online April 29, 2022; DOI: https://doi.org/10.4093/dmj.2021.0370

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Background
We investigated whether Lactobacillus plantarum strain LMT1-48, isolated from Korean fermented foods and newborn feces, is a suitable probiotic supplement to treat overweight subjects.
Methods
In this randomized, double-blind, placebo-controlled clinical trial, 100 volunteers with a body mass index of 25 to 30 kg/m² were assigned randomly (1:1) to receive 2×10¹⁰ colony forming units of LMT1-48 or to a placebo treatment group. Body composition was measured by dual-energy X-ray absorptiometry, and abdominal visceral fat area (VFA) and subcutaneous fat area were measured by computed tomography scanning. Changes in body fat, VFA, anthropometric parameters, and biomarkers were compared between the two treatment groups (ClinicalTrials.gov number: NCT03759743).
Results
After 12 weeks of treatment, the body weight decreased significantly from 76.6±9.4 to 75.7±9.2 kg in the LMT1-48 group but did not change in the placebo group (P=0.022 between groups). A similar pattern was found in abdominal VFA between the two groups (P=0.041). Serum insulin levels, the corresponding homeostasis model assessment of insulin resistance, and leptin levels decreased in the LMT1-48 group but increased in the placebo group (all P<0.05). Decrease in body weight and body mass index by treatment with LMT1-48 was correlated with increase in Lactobacillus levels significantly. LMT1-48 also increased Oscillibacter levels significantly, which were negatively correlated with triglyceride and alanine transaminase levels.
Conclusion
Administration of LMT1-48 decreased body weight, abdominal VFA, insulin resistance, and leptin levels in these subjects with overweight, suggesting its anti-obesogenic therapeutic potential.

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Beneficial effects of the probiotics and synbiotics supplementation on anthropometric indices and body composition in adults: A systematic review and meta‐analysis
Saeede Saadati, Kaveh Naseri, Omid Asbaghi, Mohsen Yousefi, Elnaz Golalipour, Barbora de Courten
Obesity Reviews.2024;[Epub] CrossRef
The Effect of Lactobacillus plantarum on the Fecal Microbiota, Short Chain Fatty Acids, Odorous Substances, and Blood Biochemical Indices of Cats
Bing Han, Shukun Liang, Jintao Sun, Hui Tao, Zhenlong Wang, Baosheng Liu, Xiumin Wang, Jie Liu, Jinquan Wang
Microorganisms.2024; 12(1): 91. CrossRef
Natto alleviates hyperlipidemia in high-fat diet-fed mice by modulating the composition and metabolic function of gut microbiota
Le-Yuan Shang, Shuo Zhang, Min Zhang, Xiao-Dong Sun, Qi Wang, Yu-Jie Liu, Yan-Ni Zhao, Mei Zhao, Peng-Jiao Wang, Xiu-Li Gao
Journal of Functional Foods.2024; 112: 105968. CrossRef
Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity
Oladayo Emmanuel Apalowo, Grace Adeola Adegoye, Tolulope Mobolaji Obuotor
Current Issues in Molecular Biology.2024; 46(3): 1810. CrossRef
Anti-obesogenic effects of plant natural products: A focus on Korean traditional foods
Gitishree Das, Luis Alfonso Jiménez Ortega, Sandra Gonçalves, J. Basilio Heredia, Maria de Lourdes Gomes Pereira, Anabela Romano, Han-Seung Shin, Jayanta Kumar Patra
Trends in Food Science & Technology.2024; : 104470. CrossRef
A 12-Week, Single-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Design Clinical Trial for the Evaluation of the Efficacy and Safety of Lactiplantibacillus plantarum SKO-001 in Reducing Body Fat
Seon Mi Shin, Jeong-Su Park, Sang Back Kim, Young Hee Cho, Hee Seo, Hak Sung Lee
Nutrients.2024; 16(8): 1137. CrossRef
3D printing of microencapsulated Lactobacillus rhamnosus for oral delivery
Pablo Rosas-Val, Masoud Adhami, Ana Brotons-Canto, Carlos Gamazo, Juan M. Irache, Eneko Larrañeta
International Journal of Pharmaceutics.2023; 641: 123058. CrossRef
Gut commensal Kineothrix alysoides mitigates liver dysfunction by restoring lipid metabolism and gut microbial balance
Kyoung Jin Choi, Mi Young Yoon, Ji-Eun Kim, Sang Sun Yoon
Scientific Reports.2023;[Epub] CrossRef
Ameliorating Effects of Bifidobacterium longum subsp. infantis FB3-14 against High-Fat-Diet-Induced Obesity and Gut Microbiota Disorder
Ruixin Kou, Jin Wang, Ang Li, Yuanyifei Wang, Bowei Zhang, Jingmin Liu, Yi Sun, Shuo Wang
Nutrients.2023; 15(19): 4104. CrossRef
Effect of Continuous Ingestion of Bifidobacteria and Inulin on Reducing Body Fat: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Study
Yuhei Baba, Yasuo Saito, Mei Kadowaki, Naoki Azuma, Daisuke Tsuge
Nutrients.2023; 15(24): 5025. CrossRef
A Review of the Potential of Probiotic Bacteria in Managing the Body Weight of Obese Individuals
A Didban, L Manafi, R Mahmoudi
Journal of Health and Hygiene.2023; 14(4): 388. CrossRef
Plant-Derived Lactobacillus paracasei IJH-SONE68 Improves the Gut Microbiota Associated with Hepatic Disorders: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial
Narandalai Danshiitsoodol, Masafumi Noda, Keishi Kanno, Tomoyuki Uchida, Masanori Sugiyama
Nutrients.2022; 14(21): 4492. CrossRef

Metabolic Risk/Epidemiology
Maternal Hyperglycemia during Pregnancy Increases Adiposity of Offspring: Hye Rim Chung, Joon Ho Moon, Jung Sub Lim, Young Ah Lee, Choong Ho Shin, Joon-Seok Hong, Soo Heon Kwak, Sung Hee Choi, Hak Chul Jang; Diabetes Metab J. 2021;45(5):730-738. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0154

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Background
The effect of intrauterine hyperglycemia on fat mass and regional fat proportion of the offspring of mothers with gestational diabetes mellitus (OGDM) remains to be determined.
Methods
The body composition of OGDM (n=25) and offspring of normoglycemic mothers (n=49) was compared using dualenergy X-ray absorptiometry at age 5 years. The relationship between maternal glucose concentration during a 100 g oral glucose tolerance test (OGTT) and regional fat mass or proportion was analyzed after adjusting for maternal prepregnancy body mass index (BMI).
Results
BMI was comparable between OGDM and control (median, 16.0 kg/m² vs. 16.1 kg/m² ). Total, truncal, and leg fat mass were higher in OGDM compared with control (3,769 g vs. 2,245 g, P=0.004; 1,289 g vs. 870 g, P=0.017; 1,638 g vs. 961 g, P=0.002, respectively), whereas total lean mass was lower in OGDM (15,688 g vs. 16,941 g, P=0.001). Among OGDM, total and truncal fat mass were correlated with fasting and 3-hour glucose concentrations of maternal 100 g OGTT during pregnancy (total fat mass, r=0.49, P=0.018 [fasting], r=0.473, P=0.023 [3-hour]; truncal fat mass, r=0.571, P=0.004 [fasting], r=0.558, P=0.006 [3-hour]), but there was no correlation between OGDM leg fat mass and maternal OGTT during pregnancy. Regional fat indices were not correlated with concurrent maternal 75 g OGTT values.
Conclusion
Intrauterine hyperglycemia is associated with increased fat mass, especially truncal fat, in OGDM aged 5 years.

Citations

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Advances in free fatty acid profiles in gestational diabetes mellitus
Haoyi Du, Danyang Li, Laura Monjowa Molive, Na Wu
Journal of Translational Medicine.2024;[Epub] CrossRef
High-fat diet during pregnancy lowers fetal weight and has a long-lasting adverse effect on brown adipose tissue in the offspring
Mihoko Yamaguchi, Jun Mori, Nozomi Nishida, Satoshi Miyagaki, Yasuhiro Kawabe, Takeshi Ota, Hidechika Morimoto, Yusuke Tsuma, Shota Fukuhara, Takehiro Ogata, Takuro Okamaura, Naoko Nakanishi, Masahide Hamaguchi, Hisakazu Nakajima, Michiaki Fukui, Tomoko I
Journal of Developmental Origins of Health and Disease.2023; 14(2): 261. CrossRef
Prediction of gestational diabetes mellitus in Asian women using machine learning algorithms
Byung Soo Kang, Seon Ui Lee, Subeen Hong, Sae Kyung Choi, Jae Eun Shin, Jeong Ha Wie, Yun Sung Jo, Yeon Hee Kim, Kicheol Kil, Yoo Hyun Chung, Kyunghoon Jung, Hanul Hong, In Yang Park, Hyun Sun Ko
Scientific Reports.2023;[Epub] CrossRef
Effects of early standardized management on the growth trajectory of offspring with gestational diabetes mellitus at 0–5 years old: a preliminary longitudinal study
Bingbing Guo, Jingjing Pei, Yin Xu, Yajie Wang, Xinye Jiang
Scientific Reports.2023;[Epub] CrossRef
Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications
Joon Ho Moon, Hak Chul Jang
Diabetes & Metabolism Journal.2022; 46(1): 3. CrossRef
Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus
Yea Eun Kang, Hyon-Seung Yi, Min-Kyung Yeo, Jung Tae Kim, Danbit Park, Yewon Jung, Ok Soon Kim, Seong Eun Lee, Ji Min Kim, Kyong Hye Joung, Ju Hee Lee, Bon Jeong Ku, Mina Lee, Hyun Jin Kim
Journal of Korean Medical Science.2022;[Epub] CrossRef

Basic Research
Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men: Laura G.M. Janssen, Andrea D. van Dam, Mark J.W. Hanssen, Sander Kooijman, Kimberly J. Nahon, Hanneke Reinders, Ingrid M. Jazet, Wouter D. van Marken Lichtenbelt, Patrick C.N. Rensen, Natasha M. Appelman-Dijkstra, Mariëtte R. Boon; Diabetes Metab J. 2020;44(2):326-335. Published online October 31, 2019; DOI: https://doi.org/10.4093/dmj.2019.0031

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Background

South Asians generally have an unfavourable metabolic phenotype compared with white Caucasians, including central obesity and insulin resistance. The Wnt protein family interacts with insulin signaling, and impaired Wnt signaling is associated with adiposity and type 2 diabetes mellitus. We aimed to investigate Wnt signaling in relation to insulin signaling in South Asians compared with white Caucasians.

Methods

Ten Dutch South Asian men with prediabetes and overweight or obesity and 10 matched Dutch white Caucasians were included. Blood samples were assayed for the Wnt inhibitor sclerostin. Subcutaneous white adipose tissue (WAT) and skeletal muscle biopsies were assayed for Wnt and insulin signaling gene expression with quantitative reverse transcription polymerase chain reaction (Clinicaltrials.gov NCT02291458).

Results

Plasma sclerostin was markedly higher in South Asians compared with white Caucasians (+65%, P<0.01). Additionally, expression of multiple Wnt signaling genes and key insulin signaling genes were lower in WAT in South Asians compared with white Caucasians. Moreover, in WAT in both ethnicities, Wnt signaling gene expression strongly positively correlated with insulin signaling gene expression. In skeletal muscle, WNT10B expression in South Asians was lower, but expression of other Wnt signaling and insulin signaling genes was comparable between ethnicities. Wnt and insulin signaling gene expression also positively correlated in skeletal muscle, albeit less pronounced.

Conclusion

South Asian men with overweight or obesity and prediabetes have higher plasma sclerostin and lower Wnt signaling gene expression in WAT compared with white Caucasians. We interpret that reduced Wnt signaling could contribute to impaired insulin signaling in South Asians.

Citations

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Insights on effects of Wnt pathway modulation on insulin signaling and glucose homeostasis for the treatment of type 2 diabetes mellitus: Wnt activation or Wnt inhibition?
Ruchi Yadav, Bhumika Patel
International Journal of Biological Macromolecules.2024; 261: 129634. CrossRef
The role of the Wnt signalling pathway in the energy metabolism of bone remodelling
Mengyuan Zhu, Zhipeng Fan
Cell Proliferation.2022;[Epub] CrossRef
Transcriptomic analysis provides a new insight: Oleuropein reverses high glucose-induced osteogenic inhibition in bone marrow mesenchymal stem cells via Wnt10b activation
An Lao, Yu Chen, Yiting Sun, Tiange Wang, Kaili Lin, Jiaqiang Liu, Jianyong Wu
Frontiers in Bioengineering and Biotechnology.2022;[Epub] CrossRef
Subcutaneous adipose tissue sclerostin is reduced and Wnt signaling is enhanced following 4‐weeks of sprint interval training in young men with obesity
Nigel Kurgan, Hashim Islam, Jennifer B. L. Matusiak, Bradley J. Baranowski, Joshua Stoikos, Val A. Fajardo, Rebecca E. K. MacPherson, Brendon J. Gurd, Panagiota Klentrou
Physiological Reports.2022;[Epub] CrossRef
Circulating Levels of Sclerostin Predict Glycemic Improvement after Sleeve Gastrectomy
Federico Carbone, Elisa Nulli Migliola, Aldo Bonaventura, Alessandra Vecchié, Stefano De Vuono, Maria Anastasia Ricci, Gaetano Vaudo, Marcello Boni, Stefano Ministrini, Graziana Lupattelli, Fabrizio Montecucco
Nutrients.2021; 13(2): 623. CrossRef
Serum sclerostin concentration is associated with specific adipose, muscle and bone tissue markers in lean adolescent females with increased physical activity
Jaak Jürimäe, Vita Karvelyte, Liina Remmel, Anna-Liisa Tamm, Priit Purge, Rita Gruodyte-Raciene, Sigitas Kamandulis, Katre Maasalu, Luis Gracia-Marco, Vallo Tillmann
Journal of Pediatric Endocrinology and Metabolism.2021; 34(6): 755. CrossRef
The complex role of Wnt ligands in type 2 diabetes mellitus and related complications
Xiaobo Nie, Xiaoyun Wei, Han Ma, Lili Fan, Wei‐Dong Chen
Journal of Cellular and Molecular Medicine.2021; 25(14): 6479. CrossRef

Metabolic Risk/Epidemiology
Plasma CD36 and Incident Diabetes: A Case-Cohort Study in Danish Men and Women: Yeli Wang, Jingwen Zhu, Sarah Aroner, Kim Overvad, Tianxi Cai, Ming Yang, Anne Tjønneland, Aase Handberg, Majken K. Jensen; Diabetes Metab J. 2020;44(1):134-142. Published online October 18, 2019; DOI: https://doi.org/10.4093/dmj.2018.0273

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Background

Membrane CD36 is a fatty acid transporter implicated in the pathogenesis of metabolic disease. We aimed to evaluate the association between plasma CD36 levels and diabetes risk and to examine if the association was independent of adiposity among Danish population.

Methods

We conducted a case-cohort study nested within the Danish Diet, Cancer and Health study among participants free of cardiovascular disease, diabetes and cancer and with blood samples and anthropometric measurements (height, weight, waist circumference, and body fat percentage) at baseline (1993 to 1997). CD36 levels were measured in 647 incident diabetes cases that occurred before December 2011 and a total of 3,515 case-cohort participants (236 cases overlap).

Results

Higher plasma CD36 levels were associated with higher diabetes risk after adjusting for age, sex and other lifestyle factors. The hazard ratio (HR) comparing high versus low tertile of plasma CD36 levels was 1.36 (95% confidence interval [CI], 1.00 to 1.86). However, the association lost its significance after further adjustment for different adiposity indices such as body mass index (HR, 1.23; 95% CI, 0.87 to 1.73), waist circumference (HR, 1.21; 95% CI, 0.88 to 1.68) or body fat percentage (HR, 1.20; 95% CI, 0.86 to 1.66). Moreover, raised plasma CD36 levels were moderately associated with diabetes risk among lean participants, but the association was not present among overweight/obese individuals.

Conclusion

Higher plasma CD36 levels were associated with higher diabetes risk, but the association was not independent of adiposity. In this Danish population, the association of CD36 with diabetes risk could be either mediated or confounded by adiposity.

Citations

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The Multifunctionality of CD36 in Diabetes Mellitus and Its Complications—Update in Pathogenesis, Treatment and Monitoring
Kamila Puchałowicz, Monika Ewa Rać
Cells.2020; 9(8): 1877. CrossRef
The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond
Jun Sung Moon, Udayakumar Karunakaran, Elumalai Suma, Seung Min Chung, Kyu Chang Won
Diabetes & Metabolism Journal.2020; 44(2): 222. CrossRef

Pathophysiology
The Phospholipid Linoleoylglycerophosphocholine as a Biomarker of Directly Measured Insulin Resistance: Maria Camila Pérez-Matos, Martha Catalina Morales-Álvarez, Freddy Jean Karlo Toloza, Maria Laura Ricardo-Silgado, Jose Oscar Mantilla-Rivas, Jairo Arturo Pinzón-Cortes, Maritza Perez-Mayorga, Elizabeth Jiménez, Edwin Guevara, Carlos O Mendivil; Diabetes Metab J. 2017;41(6):466-473. Published online November 27, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.6.466

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Background

Plasma concentrations of some lysophospholipids correlate with metabolic alterations in humans, but their potential as biomarkers of insulin resistance (IR) is insufficiently known. We aimed to explore the association between plasma linoleoylglycerophosphocholine (LGPC) and objective measures of IR in adults with different metabolic profiles.

Methods

We studied 62 men and women, ages 30 to 69 years, (29% normal weight, 59% overweight, 12% obese). Participants underwent a 5-point oral glucose tolerance test (5p-OGTT) from which we calculated multiple indices of IR and insulin secretion. Fifteen participants additionally underwent a hyperinsulinemic-euglycemic clamp for estimation of insulin-stimulated glucose disposal. Plasma LGPC was determined using high performance liquid chromatography/time-of-flight mass spectrometry. Plasma LGPC was compared across quartiles defined by the IR indices.

Results

Mean LGPC was 15.4±7.6 ng/mL in women and 14.1±7.3 ng/mL in men. LGPC did not correlate with body mass in-dex, percent body fat, waist circumference, blood pressure, glycosylated hemoglobin, log-triglycerides, or high density lipoprotein cholesterol. Plasma LGPC concentrations was not systematically associated with any of the studied 5p-OGTT-derived IR indices. However, LGPC exhibited a significant negative correlation with glucose disposal in the clamp (Spearman r=−0.56, P=0.029). Despite not being diabetic, participants with higher plasma LGPC exhibited significantly higher post-challenge plasma glucose excursions in the 5p-OGTT (P trend=0.021 for the increase in glucose area under the curve across quartiles of plasma LGPC).

Conclusion

In our sample of Latino adults without known diabetes, LGPC showed potential as a biomarker of IR and impaired glucose metabolism.

Citations

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Identification of potential serum biomarkers associated with HbA1c levels in Indian type 2 diabetic subjects using NMR-based metabolomics
Saleem Yousf, Hitender S. Batra, Rakesh M. Jha, Devika M. Sardesai, Kalyani Ananthamohan, Jeetender Chugh, Shilpy Sharma
Clinica Chimica Acta.2024; 557: 117857. CrossRef
Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells
Wenqiang Sun, Mengze Li, Hanjun Ren, Yang Chen, Wei Zeng, Xiong Tan, Xianbo Jia, Shiyi Chen, Jie Wang, Songjia Lai
Animals.2024; 14(7): 1045. CrossRef
Is insulin resistance tissue-dependent and substrate-specific? The role of white adipose tissue and skeletal muscle
Diana Calderón-DuPont, Ivan Torre-Villalvazo, Andrea Díaz-Villaseñor
Biochimie.2023; 204: 48. CrossRef
Causality of genetically determined metabolites and metabolic pathways on osteoarthritis: a two-sample mendelian randomization study
Yifei Gu, Qianmei Jin, Jinquan Hu, Xinwei Wang, Wenchao Yu, Zhanchao Wang, Chen Wang, Yang Liu, Yu Chen, Wen Yuan
Journal of Translational Medicine.2023;[Epub] CrossRef
Assessing the causal effect of genetically predicted metabolites and metabolic pathways on stroke
Tianlong Zhang, Yina Cao, Jianqiang Zhao, Jiali Yao, Gang Liu
Journal of Translational Medicine.2023;[Epub] CrossRef
Lipidomics in diabetes
Eun Ji Kim, Radha Ramachandran, Anthony S. Wierzbicki
Current Opinion in Endocrinology, Diabetes & Obesity.2022; 29(2): 124. CrossRef
Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus
Margarita Ortiz-Martínez, Mirna González-González, Alexandro J. Martagón, Victoria Hlavinka, Richard C. Willson, Marco Rito-Palomares
Current Diabetes Reports.2022; 22(3): 95. CrossRef
Discrete Correlation Summation Clustering Reveals Differential Regulation of Liver Metabolism by Thrombospondin-1 in Low-Fat and High-Fat Diet-Fed Mice
Steven M. Bronson, Brian Westwood, Katherine L. Cook, Nancy J. Emenaker, Mark C. Chappell, David D. Roberts, David R. Soto-Pantoja
Metabolites.2022; 12(11): 1036. CrossRef
Metabolic Dysfunction Biomarkers as Predictors of Early Diabetes
Carla Luís, Pilar Baylina, Raquel Soares, Rúben Fernandes
Biomolecules.2021; 11(11): 1589. CrossRef
Serum metabolomics analysis of mice that received repeated airway exposure to a water-soluble PM2.5 extract
Chen Zhao, Mengyuan Niu, Shiyu Song, Jing Li, Zhonglan Su, Yong Wang, Qian Gao, Hongwei Wang
Ecotoxicology and Environmental Safety.2019; 168: 102. CrossRef

Women Are Diagnosed with Type 2 Diabetes at Higher Body Mass Indices and Older Ages than Men: Korea National Health and Nutrition Examination Survey 2007-2010: Su Kyoung Kwon; Diabetes Metab J. 2014;38(1):74-80. Published online February 19, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.1.74

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Background

Many epidemiologic studies have shown that women with type 2 diabetes have an increased risk of developing cardiovascular disease compared with men with diabetes. The aim of this study is to elucidate whether disparities of adiposity, age and insulin resistance (IR) at the time of diabetes diagnosis exist between women and men in the adult Korean population.

Methods

Data from The Korea National Health and Nutrition Examination Survey, performed in Korea from 2007 to 2010, were used. In the survey, anthropometric data and blood samples were obtained during a fasting state. IR and β-cell function were calculated using the homeostasis model assessment (HOMA-IR and HOMA-β, respectvely).

Results

The mean age of diabetes diagnosis was 58.5 years in women and was 55.1 years in men (P=0.015). The mean body mass index (BMI) of newly diagnosed diabetes subjects was 26.1 kg/m² in women and 25.0 kg/m² in men (P=0.001). The BMI was inversely related to age in both genders, and the higher BMI in women than men was consistent throughout all age groups divided by decade. The HOMA-IR in women with diabetes is higher than in men with diabetes (7.25±0.77 vs. 5.20±0.32; P=0.012).

Conclusion

Korean adult women are diagnosed with type 2 diabetes at higher BMI and older age than men and are more insulin-resistant at the time of diabetes diagnosis. This may help explain why women with diabetes have an increased risk of developing cardiovascular disease after the diagnosis of diabetes, compared to men.

Citations

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Abdallah Al-Salameh, Nacera El bouzegaoui, Marie Saraval-Gross
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Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews
Clyve Yu Leon Yaow, Bryan Chong, Yip Han Chin, Martin Tze Wah Kueh, Cheng Han Ng, Kai En Chan, Ansel Shao Pin Tang, Charlotte Chung, Rachel Goh, Gwyneth Kong, Mark Muthiah, Indah Sukmawati, Antonia Anna Lukito, Mark Y Chan, Chin Meng Khoo, Anurag Mehta, M
European Journal of Preventive Cardiology.2023; 30(12): 1227. CrossRef
Indian Phenotype Characteristics Among Patients with Type 2 Diabetes Mellitus: Insights from a Non-interventional Nationwide Registry in India
Sanjay Kalra, Ambrish Mithal, Abdul Hamid Zargar, Bipin Sethi, Mala Dharmalingam, Sujoy Ghosh, Ranjini Sen
Endocrinology.2022; 18(1): 63. CrossRef
Recreational training improves cardiovascular adaptations, metabolic profile and mental health of elderly women with type-2 diabetes mellitus
Andrea Sanches, Vinicius Guzzoni, Vania C. dos R. Miranda, Laís Bonagurio Peressim, Suellen Rocha, Patrícia Oliveira de Lima, Fernanda Klein Marcondes, Ana Paula Tanno, Tatiana Sousa Cunha
Health Care for Women International.2021; 42(11): 1279. CrossRef
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Neda Rasouli, Naji Younes, Kristina M. Utzschneider, Silvio E. Inzucchi, Ashok Balasubramanyam, Andrea L. Cherrington, Faramarz Ismail-Beigi, Robert M. Cohen, Darin E. Olson, Ralph A. DeFronzo, William H. Herman, John M. Lachin, Steven E. Kahn, Jill P. Cr
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Sex/Gender Differences in Obesity Prevalence, Comorbidities, and Treatment
Ashley J. Cooper, Sapana R. Gupta, Afaf F. Moustafa, Ariana M. Chao
Current Obesity Reports.2021; 10(4): 458. CrossRef
Age-, sex- and ethnicity-related differences in body weight, blood pressure, HbA1c and lipid levels at the diagnosis of type 2 diabetes relative to people without diabetes
Alison K. Wright, Paul Welsh, Jason M. R. Gill, Evangelos Kontopantelis, Richard Emsley, Iain Buchan, Darren M. Ashcroft, Martin K. Rutter, Naveed Sattar
Diabetologia.2020; 63(8): 1542. CrossRef
Impact of Gender on Type II Diabetes Glycemic and Cardiovascular Markers Control and Treatment
Khaled A. Alswat
Pakistan Journal of Biological Sciences.2020; 23(12): 1643. CrossRef
Preadipocytes of obese humans display gender-specific bioenergetic responses to glucose and insulin
Michaela Keuper, Lucia Berti, Bernhard Raedle, Stephan Sachs, Anja Böhm, Louise Fritsche, Andreas Fritsche, Hans-Ulrich Häring, Martin Hrabě de Angelis, Martin Jastroch, Susanna M. Hofmann, Harald Staiger
Molecular Metabolism.2019; 20: 28. CrossRef
Risk of all-cause and CHD mortality in women versus men with type 2 diabetes: a systematic review and meta-analysis
Guodong Xu, Dingyun You, Liping Wong, Donghui Duan, Fanqian Kong, Xiaohong Zhang, Jinshun Zhao, Wenhua Xing, Liyuan Han, Li Li
European Journal of Endocrinology.2019; 180(4): 243. CrossRef
Gut flora, diet and intestinal metabolism on cardiovascular risk
Deepak Bhatnagar
Current Opinion in Lipidology.2015; 26(2): 148. CrossRef

Relation of Absolute or Relative Adiposity to Insulin Resistance, Retinol Binding Protein-4, Leptin, and Adiponectin in Type 2 Diabetes: You Lim Kim, Tae Kyun Kim, Eun Sun Cheong, Dong Geum Shin, Gyu Sik Choi, Jihye Jung, Kyung-Ah Han, Kyung Wan Min; Diabetes Metab J. 2012;36(6):415-421. Published online December 12, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.6.415

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Background

Central fat mass (CFM) correlates with insulin resistance and increases the risk of type 2 diabetes and cardiovascular complications; however, peripheral fat mass (PFM) is associated with insulin sensitivity. The aim of this study was to investigate the relation of absolute and relative regional adiposity to insulin resistance index and adipokines in type 2 diabetes.

Methods

Total of 83 overweighted-Korean women with type 2 diabetes were enrolled, and rate constants for plasma glucose disappearance (K_ITT) and serum adipokines, such as retinol binding protein-4 (RBP4), leptin, and adiponectin, were measured. Using dual X-ray absorptiometry, trunk fat mass (in kilograms) was defined as CFM, sum of fat mass on the lower extremities (in kilograms) as PFM, and sum of CFM and PFM as total fat mass (TFM). PFM/TFM ratio, CFM/TFM ratio, and PFM/CFM ratio were defined as relative adiposity.

Results

Median age was 55.9 years, mean body mass index 27.2 kg/m², and mean HbA1c level 7.12±0.84%. K_ITT was positively associated with PMF/TFM ratio, PMF/CFM ratio, and negatively with CFM/TFM ratio, but was not associated with TFM, PFM, or CFM. RBP4 levels also had a significant relationship with PMF/TFM ratio and PMF/CFM ratio. Adiponectin, leptin, and apolipoprotein A levels were related to absolute adiposity, while only adiponectin to relative adiposity. In correlation analysis, K_ITT in type 2 diabetes was positively related with HbA1c, fasting glucose, RBP4, and free fatty acid.

Conclusion

These results suggest that increased relative amount of peripheral fat mass may aggravate insulin resistance in type 2 diabetes.

Citations

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Review

Molecular Mechanisms of Appetite Regulation: Ji Hee Yu, Min-Seon Kim; Diabetes Metab J. 2012;36(6):391-398. Published online December 12, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.6.391

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Abstract PDF PubReader

The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

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Original Articles

Prevention of Diabetes by Fenofibrate in OLETF Rats: Hepatic Mechanism for Reducing Visceral Adiposity.: Hye Jeong Lee, Mi Kyoung Park, Kyung Il Lee, Young Jun An, Ji Min Kim, Ja Young Park, Young Han, Sook Hee Hong, Sun Seob Choi, Young Hyun Yoo, Joon Duk Suh, Duk Kyu Kim; Korean Diabetes J. 2007;31(1):63-74. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.63

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Abstract PDF

BACKGROUND
The aim of this study is to evaluate the hepatic mechanism of fenofibrate that has the diabetes protective action in rats. METHODS: We chose OLETF rats and divided them into three groups. Fenofibrate (DF) group was fed with diet and fenofibrate (300 mg/kg/day). Paired feeding (Dd) group and free diet (DD) group were fed with diet. After 36 weeks of treatment, all the rats were sacrificed. RESULTS: The fasting blood glucose level of DF group (8.5 +/- 0.9 mmol/L) showed normal. The fasting blood glucose level of Dd group (22.4 +/- 3.0 mmol/L) and DD group (16.9 +/- 3.7 mmol/L) showed significantly increased than that of DF group (P < 0.01, respectively). The body weight, visceral adipose tissue and subcutaneous adipose tissue of DF group were significantly decreased compared to those of Dd and DD groups (P < 0.01, P < 0.05, P < 0.05). DF group showed significantly increased state-3 respiration rate, ATP synthetic activity, state-4 respiration rate and their blood beta-keton body levels than those of control groups (P < 0.01, respectively). DF group showed normal morphology of hepatocytes but DD and Dd groups showed hepatic steatosis with mitochondrial swellings. CONCLUSION: Chronic fenofibrate treatment prevents the development of diabetes in OLETF rats with inhibiting gain of body weight and abdominal adiposity. The hepatic mechanism for reducing visceral adiposity is that fenofibrate leads to increasing oxidative phosphorylation, uncoupling and ketogenesis as well as increasing beta-oxidation of fatty acids. Moreover, fenofibrate treatment prevents the development of hepatic steatosis.

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The Differences of Metabolic Syndrome Risk Factors according to Obesity and Abdominal Obesity in Elderly Korean Women
Kyung-A Shin
The Korean Journal of Clinical Laboratory Science.2016; 48(4): 304. CrossRef
Effects of Soybean and DJI Chungkukjang Powder on Blood Glucose and Serum Lipid Reduction in db/db Mice
Jae-Joon Lee, Ah-Ra Kim, Hae-Choon Chang, Hae-Ok Jung, Myung-Yul Lee
Journal of the Korean Society of Food Science and Nutrition.2012; 41(8): 1086. CrossRef
Comparative analysis of fat and muscle proteins in fenofibratefed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein
Jong-Ryeal Hahm, Jin-Sook Ahn, Hae-Sook Noh, Seon-Mi Baek, Ji-Hye Ha, Tae-Sik Jung, Yong-Jun An, Duk-Kyu Kim, Deok-Ryong Kim
BMB Reports .2010; 43(5): 337. CrossRef
Comparative analysis of fat and muscle proteins in fenofibratefed type II diabetic OLETF rats: the fenofibrate-dependent expression of PEBP or C11orf59 protein
Jong-Ryeal Hahm, Jin-Sook Ahn, Hae-Sook Noh, Seon-Mi Baek, Ji-Hye Ha, Tae-Sik Jung, Yong-Jun An, Duk-Kyu Kim, Deok-Ryong Kim
BMB Reports.2010; 43(5): 337. CrossRef

Exercise and Fenofibrate Reduces Body Adiposity Synergistically in OLETF Rats.: Young Jun An, Hre Jeong Lee, Mi Kyoung Park, Kyung Il Lee, In Young Koh, Dong Sik Jung, Ah Young Kang, Duk Kyu Kim; Korean Diabetes J. 2004;28(2):131-138. Published online April 1, 2004

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Abstract PDF: BACKGROUND
The PPAR alpha activator, Fenofibrate, is a pharmacological ligand, which induces beta-oxidation of long chain fatty acids in the mitochondria of hepatocytes. The beta-oxidation induced by exogenous PPAR alpha activators may be operated maximally when the sustained production of energy substrate in the liver is required by working muscles due to continued exercise. The aim of this study was to determine whether the combination therapy of exercise and Fenofibrate could synergistically reduce body adiposity in OLETF rats. METHODS: Twenty-eight male OLETF rats(13 wk old) were divided into four groups. The diet(n=7) and exercise groups(n=7) were fed with chow for 12 weeks. The Fenofibrate(n=7) and combined treatment(exercise and Fenofibrate) groups (n=7) were fed with Fenofibrate(32mg/kg/day) mixed chow for 12 weeks. The animals in the exercise and combined treatment groups were exercised by running on a treadmill for 12 weeks. At 24 weeks of age, all the rats were sacrificed, and examined by biochemical tests and had their adipose tissue weight measured. RESULTS: There were no significant changes in the retroperitoneal and subcutaneous fats between the diet and Fenofibrate groups, but there were between the diet and combined treatment groups(P<0.05). CONCLUSION: Exercise combined with Fenofibrate synergistically reduces body adiposity in OLETF rats

Plasma Leptin Concentration, Obesity, and Insulin Resistance in Healthy Korean Population.: Dong Lim Kim, Nan Hee Kim, Dong Hyun Shin, Sin Gon Kim, Kyung Mook Choi, Jin Kwan Kim, Chol Shin, Seung Gwan Lee, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2002;26(2):100-111. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Leptin is a hormone that regulates food intake and body weight. It has been demonstrated that the plasma leptin levels correlates with body adiposity. Increased adiposity is accompanied by a low insulin sensitivity, which turns into insulin resistance. Recent studies suggest a complex interrelationship between leptin and insulin or insulin resistance. Therefore, the relationship between leptin and the variables of body adiposity, and insulin resistance in a non-diabetic population was examined. METHODS: 555 healthy non-diabetic people aged 20 to 80 were enrolled in this study. Leptin was measured by the mean radioimmunoassay. Multiple logistic regression analysis was performed with leptin as a dependent variable and with age, sex, BP, the lipid profile, the fasting plasma glucose levels, HOMA-IR and the trunk fat contents as independent variables. RESULTS: The plasma leptin concentrations were higher in women than in men. The leptin concentrations correlated with the body fat content, BMI and HOMA-IR but, less so with age, the fasting plasma glucose levels, the postprandial glucose levels, total cholesterol and LDL-cholesterol levels. After adjusting for the body mass index, the leptin levels significantly correlated with both the body fat content and the HOMA-IR. The results between males and females were similar when the data was analyzed after dividing by gender. Gender, the trunk fat content, HOMA-IR, and the total cholesterol and HDL cholesterol levels were independent variables which influences the log transformed leptin in multiple logistic regression analysis. When the subjects were grouped according to the number of insulin resistance syndrome including dyslipidemia, obesity, hypertension, and glucose intolerance, there was a linear increase in the leptin concentration with an increase in the number of the components of insulin resistance syndrome. CONCLUSION: The plasma leptin concentrations are related to adiposity, insulin resistance, and dyslipidemia in the non-diabetic Korean population. The relationship between leptin and insulin resistance independent of body fat suggests that insulin resistance might play some role in the development of hyperleptinemia and vice versa

Serum Plasema Leptin Levels, Abdominal Obesity, and Insulin Resistance in Type 2 Diabetic Patients.: Dae Won Jun, Sung Hun Kim, Jae Hyung Lee, Woong Hwan Choi, Yong Soo Park, Tae Hwa Kim; Korean Diabetes J. 2000;24(2):216-224. Published online January 1, 2001

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Abstract PDF: BACKGROUND
There is growing evidence for a adipoinsular axis, between adipose tissue and pancreatic beta cells via the hormones leptin and insulin, in mice models, Insulin is adipogenic and increases the production of leptin by adipose tissue, Leptin feeds back to reduce both insulin secretion and insulin gene expression. But human obesity is a complex disorder, with many factors playing a parts; the pathophysiology of leptin is not as simple as it seems to be in mice models of obesity. We therefore explored the dysregulation between leptin and insulin concentration in human model. METHOD: Using radioimmunoassay, we measured serum leptin concentrations in Type 2 diabetic patients (male 26, male 52). Using body composition, we measured total and regional adiposity. The data were analyzed using t-tast to test difference in serum leptin concentration, and other factors were evaluated by partial correlation analysis. RESULT: Serum leptin concentrations in both sex was strongly and positively correlated with total adiposity (r=0.588, p<0.001), Serum leptin concentration was correlated with serum insulin concentration (r=0.41, p=0.002) even after adjusting for adiposity in both sex (r=0.32, p=0.021). Serum leptin concentration was more highly correlated with abdominal adiposity than peripheral adiposity(r=0.693 vs r=0,628). Leptin concentration were higher in women than men, even at the same adiposity, However, no independent association was seen between leptin and hypertension as well as total cholesterol. CONCLUSION: Serum leptin concentration was correlated with serum insulin concentration even after adjusting for adiposity in both sex, In human, such a putative loss of leptin reception by beta cell could result in dysregulation of the adipoinsular axls and a corresponding failure to suppress insulin secretion, resulting in chronic hyperinsutinemia.

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