Diabetes & Metabolism Journal

Erratum

Hyperinsulinemia in Obesity, Inflammation, and Cancer: Anni M.Y. Zhang, Elizabeth A. Wellberg, Janel L. Kopp, James D. Johnson; Diabetes Metab J. 2021;45(4):622-622. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0131; Corrects: Diabetes Metab J 2021;45(3):285

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Letter

Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78): Ja Young Jeon; Diabetes Metab J. 2021;45(4):613-614. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0129

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The relationships between variables of glycated hemoglobin and diabetes distress in patients with type 1 and type 2 diabetes mellitus
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Corrigendum

Early Glycosylated Hemoglobin Target Achievement Predicts Clinical Outcomes in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: Joonyub Lee, Jae Hyoung Cho; Diabetes Metab J. 2021;45(4):621-621. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0119; Corrects: Diabetes Metab J 2021;45(3):337

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Dynamic Detection of HbA1c Using a Silicon Nanowire Field Effect Tube Biosensor
Hang Chen, Lijuan Deng, Jialin Sun, Hang Li, Xiaoping Zhu, Tong Wang, Yanfeng Jiang
Biosensors.2022; 12(11): 916. CrossRef

Response

Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19 (Diabetes Metab J 2021;45:251-9): Sang Youl Rhee; Diabetes Metab J. 2021;45(4):619-620. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0118

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COVID-19 Outcomes and Diabetes Mellitus: A Comprehensive Multicenter Prospective Cohort Study
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Letter

Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19 (Diabetes Metab J 2021;45:251-9): Guntram Schernthaner; Diabetes Metab J. 2021;45(4):615-616. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0081

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The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence?
Leszek Czupryniak, Dror Dicker, Roger Lehmann, Martin Prázný, Guntram Schernthaner
Cardiovascular Diabetology.2021;[Epub] CrossRef

Reviews

Metabolic Risk/Epidemiology
Computed Tomography-Derived Myosteatosis and Metabolic Disorders: Iva Miljkovic, Chantal A. Vella, Matthew Allison; Diabetes Metab J. 2021;45(4):482-491. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0277

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The role of ectopic adipose tissue infiltration into skeletal muscle (i.e., myosteatosis) for metabolic disorders has received considerable and increasing attention in the last 10 years. The purpose of this review was to evaluate and summarize existing studies focusing on computed tomography (CT)-derived measures of myosteatosis and metabolic disorders. There is consistent evidence that CT-derived myosteatosis contributes to dysglycemia, insulin resistance, type 2 diabetes mellitus, and inflammation, and, to some extent, dyslipidemia, independent of general obesity, visceral fat, and other relevant risk factors, suggesting that it may serve as a tool for metabolic risk prediction. Identification of which muscles should be examined, and the standardized CT protocols to be employed, are necessary to enhance the applicability of findings from epidemiologic studies of myosteatosis. Additional and longer longitudinal studies are necessary to confirm a role of myosteatosis in the development of type 2 diabetes mellitus, and examine these associations in a variety of muscles across multiple race/ethnic populations. Given the emerging role of myosteatosis in metabolic health, well-designed intervention studies are needed to investigate relevant lifestyle and pharmaceutical approaches.

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Cardiovascular Risk/Epidemiology
Management of Cardiovascular Risk in Perimenopausal Women with Diabetes: Catherine Kim; Diabetes Metab J. 2021;45(4):492-501. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0262

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Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of coronary heart disease events increases in postmenopausal women with diabetes. Randomized studies have conflicted regarding the beneficial impact of estrogen therapy upon intermediate cardiovascular disease markers and events. Therefore, estrogen therapy is not currently recommended for indications other than symptom management. However, for women at low risk of adverse events, estrogen therapy can be used to minimize menopausal symptoms. The risk of adverse events can be estimated using risk engines for the calculation of cardiovascular risk and breast cancer risk in conjunction with screening tools such as mammography. Use of estrogen therapy, statins, and anti-platelet agents can be guided by such calculators particularly for younger women with diabetes. Risk management remains focused upon lifestyle behaviors and achieving optimal levels of cardiovascular risk factors, including lipids, glucose, and blood pressure. Use of pharmacologic therapies to address these risk factors, particularly specific hypoglycemic agents, may provide some additional benefit for risk prevention. The minimal benefit for women with limited life expectancy and risk of complications with intensive therapy should also be considered.

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Original Articles

Complications
Study on Risk Factors of Peripheral Neuropathy in Type 2 Diabetes Mellitus and Establishment of Prediction Model: Birong Wu, Zheyun Niu, Fan Hu; Diabetes Metab J. 2021;45(4):526-538. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0100

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Background
Diabetic peripheral neuropathy (DPN) is one of the most serious complications of type 2 diabetes mellitus (T2DM). DPN increases the risk of ulcers, foot infections, and noninvasive amputations, ultimately leading to long-term disability.
Methods
Seven hundred patients with T2DM were investigated from 2013 to 2017 in the Sanlin community by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 681 patients (19 missing) were investigated using a questionnaire, physical examination, biochemical index test, and follow-up Toronto clinical scoring system (TCSS) test. Patients with a TCSS score ≥6 points were diagnosed with DPN. After removing missing values, 612 patients were divided into groups in a 3:1 ratio for external validation. Using different Lasso analyses (misclassification error, mean squared error, –2log-likelihood, and area under curve) and a logistic regression analysis of the training set, models A, B, C, and D were established. The receiver operating characteristic (ROC) curve, calibration plot, dynamic component analysis (DCA) measurements, net classification improvement (NRI) and integrated discrimination improvement (IDI) were used to validate discrimination and clinical practicality of the model.
Results
Through data analysis, model A (containing four factors), model B (containing five factors), model C (containing seven factors), and model D (containing seven factors) were built. After calibration, ROC curve, DCA, NRI and IDI, models C and D exhibited better accuracy and greater predictive power.
Conclusion
Four prediction models were established to assist with the early screening of DPN in patients with T2DM. The influencing factors in model C and D are more important factors for patients with T2DM diagnosed with DPN.

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Complications
Renal Tubular Damage Marker, Urinary N-acetyl-β-D-Glucosaminidase, as a Predictive Marker of Hepatic Fibrosis in Type 2 Diabetes Mellitus: Hae Kyung Kim, Minyoung Lee, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee; Diabetes Metab J. 2022;46(1):104-116. Published online July 13, 2021; DOI: https://doi.org/10.4093/dmj.2020.0273

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Background
Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM.
Methods
A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured.
Results
Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P<0.01).
Conclusion
The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.

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Short Communication

Type 1 Diabetes
Real-World Analysis of Therapeutic Outcome in Type 1 Diabetes Mellitus at a Tertiary Care Center: Antonia Kietaibl, Michaela Riedl, Latife Bozkurt; Diabetes Metab J. 2022;46(1):149-153. Published online July 6, 2021; DOI: https://doi.org/10.4093/dmj.2020.0267

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Abstract PDF PubReader ePub: Insulin replacement in type 1 diabetes mellitus (T1DM) needs intensified treatment, which can either be performed by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). This retrospective analysis of a real-world scenario aimed to evaluate whether glycaemic and cardiovascular risk factors could be controlled with CSII outclass MDI as suggested by recent evidence. Data from patients with either insulin pump (n=68) or injection (n=224) therapy at an Austrian tertiary care centre were analysed between January 2016 and December 2017. There were no significant differences with regard to the latest glycosylated hemoglobin, cardiovascular risk factor control or diabetes-associated late complications. Hypoglycaemia was less frequent (P<0.001), sensor-augmented therapy was more common (P=0.003) and mean body mass index (BMI) was higher (P=0.002) with CSII treatment. This retrospective analysis of real-world data in T1DM did not demonstrate the superiority of insulin pump treatment with regard to glycaemic control or cardiovascular risk factor control.

Original Article

Metabolic Risk/Epidemiology
Trends and Risk Factors of Metabolic Syndrome among Korean Adolescents, 2007 to 2018: Jiun Chae, Moon Young Seo, Shin-Hye Kim, Mi Jung Park; Diabetes Metab J. 2021;45(6):880-889. Published online July 6, 2021; DOI: https://doi.org/10.4093/dmj.2020.0185

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Background
There is a lack of recent research on the changes in risk factors for metabolic syndrome (MetS) in the Asian pediatric population. We aimed to determine the 12-year trends in the prevalence of MetS and relevant lifestyle factors such as smoking, exercise, and calorie intake among Korean adolescents.
Methods
We investigated trends in MetS and lifestyle factors among 6,308 adolescents aged 12 to 18 years from the Korea National Health and Nutrition Examination Survey, 2007 to 2018.
Results
The prevalence of MetS was stable from 2007 to 2018 (1.7% to 2.2%). There were significant increases in the prevalence of central obesity (from 8.1% to 11.2%, P=0.012) and hyperglycemia (from 5.3% to 10.4%, P<0.001) and decreases in hypo-high-density lipoprotein (HDL)-cholesterolemia (from 22.4% to 14.8%, P<0.001). Total calorie intake and calorie intake from fat significantly increased (P<0.001), whereas calorie intake from carbohydrates significantly decreased (P<0.001) during the study period. The proportions of tobacco smokers and regular walkers significantly decreased from 2007 to 2018. After controlling for all covariates, total calorie intake was positively correlated with waist circumference (P<0.05). HDL-cholesterol was negatively associated with carbohydrate consumption (P<0.01) and positively associated with fat consumption (P<0.001). Regular walking and regular strength training were associated with lower waist circumference (P<0.05). Smoking was associated with lower fasting glucose levels (P<0.01).
Conclusion
Although the prevalence rate of MetS is stable among Korean adolescents, the prevalence of central obesity and hyperglycemia has increased greatly in the recent decade. Public education on proper dietary intake and lifestyle modification is required.

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Review

Basic Research
Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis: Okamatsu-Ogura Yuko, Masayuki Saito; Diabetes Metab J. 2021;45(6):840-852. Published online June 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0291

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Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.

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Original Articles

Drug/Regimen
Effects of Teneligliptin on HbA1c levels, Continuous Glucose Monitoring-Derived Time in Range and Glycemic Variability in Elderly Patients with T2DM (TEDDY Study): Ji Cheol Bae, Soo Heon Kwak, Hyun Jin Kim, Sang-Yong Kim, You-Cheol Hwang, Sunghwan Suh, Bok Jin Hyun, Ji Eun Cha, Jong Chul Won, Jae Hyeon Kim; Diabetes Metab J. 2022;46(1):81-92. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2021.0016

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Background
To evaluate the effects of teneligliptin on glycosylated hemoglobin (HbA1c) levels, continuous glucose monitoring (CGM)-derived time in range, and glycemic variability in elderly type 2 diabetes mellitus patients.
Methods
This randomized, double-blinded, placebo-controlled study was conducted in eight centers in Korea (clinical trial registration number: NCT03508323). Sixty-five participants aged ≥65 years, who were treatment-naïve or had been treated with stable doses of metformin, were randomized at a 1:1 ratio to receive 20 mg of teneligliptin (n=35) or placebo (n=30) for 12 weeks. The main endpoints were the changes in HbA1c levels from baseline to week 12, CGM metrics-derived time in range, and glycemic variability.
Results
After 12 weeks, a significant reduction (by 0.84%) in HbA1c levels was observed in the teneligliptin group compared to that in the placebo group (by 0.08%), with a between-group least squares mean difference of –0.76% (95% confidence interval [CI], –1.08 to –0.44). The coefficient of variation, standard deviation, and mean amplitude of glycemic excursion significantly decreased in participants treated with teneligliptin as compared to those in the placebo group. Teneligliptin treatment significantly decreased the time spent above 180 or 250 mg/dL, respectively, without increasing the time spent below 70 mg/dL. The mean percentage of time for which glucose levels remained in the 70 to 180 mg/dL time in range (TIR70–180) at week 12 was 82.0%±16.0% in the teneligliptin group, and placebo-adjusted change in TIR70–180 from baseline was 13.3% (95% CI, 6.0 to 20.6).
Conclusion
Teneligliptin effectively reduced HbA1c levels, time spent above the target range, and glycemic variability, without increasing hypoglycemia in our study population.

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Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study
Harmanjit Singh, Ravi Rohilla, Shivani Jaswal, Mandeep Singla
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Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects
Harmanjit Singh, Jasbir Singh, Ravneet Kaur Bhangu, Mandeep Singla, Jagjit Singh, Farideh Javid
Expert Review of Clinical Pharmacology.2023; 16(1): 49. CrossRef
Mechanism of molecular interaction of sitagliptin with human DPP4 enzyme - New Insights
Michelangelo Bauwelz Gonzatti, José Edvar Monteiro Júnior, Antônio José Rocha, Jonathas Sales de Oliveira, Antônio José de Jesus Evangelista, Fátima Morgana Pio Fonseca, Vânia Marilande Ceccatto, Ariclécio Cunha de Oliveira, José Ednésio da Cruz Freire
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Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes
Min Jeong Park, Kyung Mook Choi
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Drug/Regimen
Efficacy and Safety of Self-Titration Algorithms of Insulin Glargine 300 units/mL in Individuals with Uncontrolled Type 2 Diabetes Mellitus (The Korean TITRATION Study): A Randomized Controlled Trial: Jae Hyun Bae, Chang Ho Ahn, Ye Seul Yang, Sun Joon Moon, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Diabetes Metab J. 2022;46(1):71-80. Published online June 16, 2021; DOI: https://doi.org/10.4093/dmj.2020.0274

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Background
To compare the efficacy and safety of two insulin self-titration algorithms, Implementing New Strategies with Insulin Glargine for Hyperglycemia Treatment (INSIGHT) and EDITION, for insulin glargine 300 units/mL (Gla-300) in Korean individuals with uncontrolled type 2 diabetes mellitus (T2DM).
Methods
In a 12-week, randomized, open-label trial, individuals with uncontrolled T2DM requiring basal insulin were randomized to either the INSIGHT (adjusted by 1 unit/day) or EDITION (adjusted by 3 units/week) algorithm to achieve a fasting self-monitoring of blood glucose (SMBG) in the range of 4.4 to 5.6 mmol/L. The primary outcome was the proportion of individuals achieving a fasting SMBG ≤5.6 mmol/L without noct urnal hypoglycemia at week 12.
Results
Of 129 individuals (age, 64.1±9.5 years; 66 [51.2%] women), 65 and 64 were randomized to the INSIGHT and EDITION algorithms, respectively. The primary outcome of achievement was comparable between the two groups (24.6% vs. 23.4%, P=0.876). Compared with the EDITION group, the INSIGHT group had a greater reduction in 7-point SMBG but a similar decrease in fasting plasma glucose and glycosylated hemoglobin. The increment of total daily insulin dose was significantly higher in the INSIGHT group than in the EDITION group (between-group difference: 5.8±2.7 units/day, P=0.033). However, body weight was significantly increased only in the EDITION group (0.6±2.4 kg, P=0.038). There was no difference in the occurrence of hypoglycemia between the two groups. Patient satisfaction was significantly increased in the INSIGHT group (P=0.014).
Conclusion
The self-titration of Gla-300 using the INSIGHT algorithm was effective and safe compared with that using the EDITION algorithm in Korean individuals with uncontrolled T2DM (ClinicalTrials.gov number: NCT03406663).

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Basal insulin titration algorithms in patients with type 2 diabetes: the simplest is the best (?)
V.I. Katerenchuk
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2023; 19(1): 72. CrossRef
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V.I. Katerenchuk, A.V. Katerenchuk
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2023; 19(3): 240. CrossRef
Time for Using Machine Learning for Dose Guidance in Titration of People With Type 2 Diabetes? A Systematic Review of Basal Insulin Dose Guidance
Camilla Heisel Nyholm Thomsen, Stine Hangaard, Thomas Kronborg, Peter Vestergaard, Ole Hejlesen, Morten Hasselstrøm Jensen
Journal of Diabetes Science and Technology.2022; : 193229682211459. CrossRef

Metabolic Risk/Epidemiology
Longitudinal Change in Myocardial Function and Clinical Parameters in Middle-Aged Subjects: A 3-Year Follow-up Study: Dong-Hyuk Cho, Hyung Joon Joo, Mi-Na Kim, Hee-Dong Kim, Do-Sun Lim, Seong-Mi Park; Diabetes Metab J. 2021;45(5):719-729. Published online June 15, 2021; DOI: https://doi.org/10.4093/dmj.2020.0132

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Background
Metabolic syndrome (MetS) is closely associated with the aging process. However, changes in metabolic conditions and cardiac function that occur in middle aged population remain unclear. We evaluated longitudinal changes in metabolic parameters and cardiac function during a 3-year period in subjects with suspected MetS.
Methods
We studied 191 participants with suspected MetS at baseline and after 3 years. Anthropometric parameters, including waist circumference (WC), and metabolic parameters, including fasting blood glucose and lipid profile were measured. Conventional echocardiography with two-dimensional speckle tracking was performed.
Results
Mean age was 56.2±4.4 years, and there were 97 women (50.8%). Men had increased WC and triglycerides (TG) (WC 91.2±6.8 cm vs. 84.0±8.0 cm, P<0.001; TG 184.4±116.3 mg/dL vs. 128.2±53.6 mg/dL, P<0.001), and reduced global longitudinal strain (GLS) (–15.4%±2.1% vs. –17.1%±2.0%, P<0.001) compared to women. After 3.4 years, values of WC and TG did not change in men but increased in women (all P<0.05). The absolute value of left ventricular (LV) GLS did not change in men but was reduced in women (P=0.011). Change in TG was independently associated with worsening of LV GLS only in women (standardized β, –0.309; 95% confidence interval, –0.130 to –0.009; P=0.025).
Conclusion
In middle aged population, a vulnerable period for metabolic disturbance, cardiac remodeling tended to progress, which was prominent in women. Progression of adiposity and dyslipidemia after menopause may accelerate subclinical cardiac remodeling in middle-aged women. Lifestyle modification and medical interventions may help prevent further cardiac dysfunction in these subjects.

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Dan Zhou, Zhongwen Ye, Zhiqiang Nie, Chaolei Chen, Songyuan Luo, Mengqi Yan, Jiabin Wang, Yingqing Feng
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