Diabetes & Metabolism Journal

Original Articles

Cardiovascular Risk/Epidemiology
Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression: Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim; Received February 10, 2024 Accepted May 13, 2024 Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0066 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus.
Methods
Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis.
Results
During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration.
Conclusion
Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Cardiovascular Risk/Epidemiology
Comparison of on-Statin Lipid and Lipoprotein Levels for the Prediction of First Cardiovascular Event in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jimi Choi, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2023;47(6):837-845. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0217

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Abstract PDF Supplementary Material PubReader ePub: Background
A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented.
Methods
From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C.
Results
MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL.
Conclusion
On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

Review

Cardiovascular Risk/Epidemiology
Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus: Takayoshi Sasako, Toshimasa Yamauchi, Kohjiro Ueki; Diabetes Metab J. 2023;47(2):185-197. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0325

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In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

Citations

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Current Nutrition Reports.2024; 13(2): 166. CrossRef
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Song Lu, Qun Wang, Hengcheng Lu, Maobin Kuang, Min Zhang, Guotai Sheng, Yang Zou, Xiaoping Peng
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Takayoshi Sasako
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Alfredo Caturano, Raffaele Galiero, Maria Rocco, Giuseppina Tagliaferri, Alessia Piacevole, Davide Nilo, Giovanni Di Lorenzo, Celestino Sardu, Erica Vetrano, Marcellino Monda, Raffaele Marfella, Luca Rinaldi, Ferdinando Carlo Sasso
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Ji Yoon Kim, Jiyoon Lee, Sin Gon Kim, Nam Hoon Kim
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Sarcopenia: Loss of mighty armor against frailty and aging
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Original Articles

Metabolic Risk/Epidemiology
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus: So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim; Diabetes Metab J. 2022;46(1):140-148. Published online August 9, 2021; DOI: https://doi.org/10.4093/dmj.2021.0023

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Background
To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM).
Methods
We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age.
Results
Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m². The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles.
Conclusion
In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.

Citations

Citations to this article as recorded by

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
Modulation of gut microbiota and lipid metabolism in rats fed high-fat diets by Ganoderma lucidum triterpenoids
Aijun Tong, Weihao Wu, Zhengxin Chen, Jiahui Wen, Ruibo Jia, Bin Liu, Hui Cao, Chao Zhao
Current Research in Food Science.2023; 6: 100427. CrossRef
Fetal Abdominal Obesity Detected at 24 to 28 Weeks of Gestation Persists until Delivery Despite Management of Gestational Diabetes Mellitus (Diabetes Metab J 2021;45:547-57)
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Obesity and Metabolic Syndrome
Comparison of Competitive Models of Metabolic Syndrome Using Structural Equation Modeling: A Confirmatory Factor Analysis: Karimollah Hajian-Tilaki; Diabetes Metab J. 2018;42(5):433-441. Published online October 22, 2018; DOI: https://doi.org/10.4093/dmj.2018.0010

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Abstract PDF PubReader

Background

The purpose of this study was to apply the structural equation modeling (SEM) to compare the fitness of different competing models (one, two, and three factors) of the metabolic syndrome (MetS) in Iranian adult population.

Methods

Data are given on the cardiometabolic risk factors of 841 individuals with nondiabetic adults from a cross-sectional population-based study of glucose, lipids, and MetS in the north of Iran. The three conceptual hypothesized models (single factor, two correlated factors, and three correlated latent factors) were evaluated by using confirmatory factor analysis with the SEM approach. The summary statistics of correlation coefficients and the model summary fitting indexes were calculated.

Results

The findings show that a single-factor model and a two-correlated factor model had a poorer summary fitting index compared with a three-correlated factor model. All fitting criteria met the conceptual hypothesized three-correlated factor model for both sexes. However, the correlation structure between the three underlying constructs designating the MetS was higher in women than in men.

Conclusion

These results indicate the plausibility of the pathophysiology and etiology of MetS being multifactorial, rather than a single factor, in a nondiabetic Iranian adult population.

Citations

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Structural Equation Modelling for Predicting the Relative Contribution of Each Component in the Metabolic Syndrome Status Change
José E. Teixeira, José A. Bragada, João P. Bragada, Joana P. Coelho, Isabel G. Pinto, Luís P. Reis, Paula O. Fernandes, Jorge E. Morais, Pedro M. Magalhães
International Journal of Environmental Research and Public Health.2022; 19(6): 3384. CrossRef
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Liying Li, Ziqiong Wang, Muxin Zhang, Haiyan Ruan, Linxia Zhou, Xin Wei, Ye Zhu, Jiafu Wei, Sen He
Preventive Medicine Reports.2021; 24: 101618. CrossRef
Definition and early diagnosis of metabolic syndrome in children
Gunter Matthias Christian Flemming, Sarah Bussler, Antje Körner, Wieland Kiess
Journal of Pediatric Endocrinology and Metabolism.2020; 33(7): 821. CrossRef
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Pamela Mattar, Sofía Sanhueza, Gabriela Yuri, Lautaro Briones, Claudio Perez-Leighton, Assaf Rudich, Sergio Lavandero, Mariana Cifuentes
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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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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
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Steven M. Bronson, Brian Westwood, Katherine L. Cook, Nancy J. Emenaker, Mark C. Chappell, David D. Roberts, David R. Soto-Pantoja
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The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes: Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang; Diabetes Metab J. 2014;38(3):211-219. Published online June 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.3.211

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Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

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Prevalence of Dyslipidemia among Korean Adults: Korea National Health and Nutrition Survey 1998-2005: Myung Ha Lee, Hyeon Chang Kim, Song Vogue Ahn, Nam Wook Hur, Dong Phil Choi, Chang Gyu Park, Il Suh; Diabetes Metab J. 2012;36(1):43-55. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.43

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Background

Dyslipidemia is a disorder of lipid metabolism, including elevated total cholesterol, elevated triglyceride, elevated low density lipoprotein cholesterol (LDL-C), and decreased high density lipoprotein cholesterol (HDL-C). The objective of this study was to investigate recent changes in the prevalence of dyslipidemia and also the rates of awareness, treatment, and control of dyslipidemia among Korean adults.

Methods

Dyslipidemia is defined according to the National Cholesterol Education Program-Adult Treatment Panel III as total cholesterol ≥240 mg/dL, LDL-C ≥160 mg/dL, HDL-C <40 mg/dL, and triglyceride ≥200 mg/dL. The prevalence of dyslipidemia was estimated for adults aged ≥20 years using the Korea National Health and Nutrition Survey (KNHANES) in 1998 (n=6,923), 2001 (n=4,882), and 2005 (n=5,323). Rates of awareness, treatment and control of dyslipidemia were calculated for adults aged ≥30 years using the KNHANES in 2005 (n=4,654).

Results

The prevalence of dyslipidemia (aged ≥20 years) increased from 32.4% in 1998 to 42.6% in 2001 and 44.1% in 2005. Compared with the KNHANES in 1998, the prevalence of dyslipidemia was 47% (95% confidence interval [CI], 35% to 59%) higher in 2001 and 61% (95% CI, 49% to 75%) higher in 2005. In 2005, only 9.5% of people with dyslipidemia were aware of the disease, 5.2% used lipid-lowering medication, and 33.2% of patients with treatment reached treatment goals.

Conclusion

The prevalence of dyslipidemia in Korea gradually increased between 1998 and 2005. These findings suggest that more intense efforts for the prevention and treatment of dyslipidemia may lead to further improvement in the management of dyslipidemia.

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Review

Glycosphingolipid Modification: Structural Diversity, Functional and Mechanistic Integration of Diabetes: Tadashi Yamashita; Diabetes Metab J. 2011;35(4):309-316. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.309

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Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes have typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin. GSLs are usually observed in many organs ubiquitously. However, GSLs, including over 400 derivatives, participate in diverse cellular functions. Several studies indicate that GSLs might have an effect on signal transduction related to insulin receptors and epidermal growth factor receptors. GSLs may modulate immune responses by transmitting signals from the exterior to the interior of the cell. Guillain-Barré syndrome is one of the autoimmune disorders characterized by symmetrical weakness in the muscles of the legs. The targets of the immune response are thought to be gangliosides, which are one group of GSLs. Other GSLs may serve as second messengers in several signaling pathways that are important to cell survival or programmed cell death. In the search for clear evidence that GSLs may play critical roles in various biological functions, many researchers have made genetically engineered mice. Before the era of gene manipulation, spontaneous animal models or chemical-induced disease models were used.

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Original Article

The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.: Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim; Korean Diabetes J. 2009;33(6):485-493. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.485

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BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

Citations

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The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
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Journal of Atherosclerosis and Thrombosis.2024; 31(8): 1194. CrossRef
Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
Ki Won Oh
Korean Diabetes Journal.2009; 33(6): 464. CrossRef

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