Diabetes & Metabolism Journal

Original Articles

Genetics
Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women: Claudia Ha-ting Tam, Ying Wang, Chi Chiu Wang, Lai Yuk Yuen, Cadmon King-poo Lim, Junhong Leng, Ling Wu, Alex Chi-wai Ng, Yong Hou, Kit Ying Tsoi, Hui Wang, Risa Ozaki, Albert Martin Li, Qingqing Wang, Juliana Chung-ngor Chan, Yan Chou Ye, Wing Hung Tam, Xilin Yang, Ronald Ching-wan Ma; Received March 20, 2024 Accepted June 17, 2024 Published online September 20, 2024; DOI: https://doi.org/10.4093/dmj.2024.0139 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.
Methods
We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.
Results
Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; P_meta=7.6×10^-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; P_meta=3.1×10^-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.
Conclusion
Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Clinical Care/Education
Pregnancy Outcomes of Women Additionally Diagnosed as Gestational Diabetes by the International Association of the Diabetes and Pregnancy Study Groups Criteria: Min Hyoung Kim, Soo Heon Kwak, Sung-Hoon Kim, Joon Seok Hong, Hye Rim Chung, Sung Hee Choi, Moon Young Kim, Hak C. Jang; Diabetes Metab J. 2019;43(6):766-775. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2018.0192

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Background

We investigated the pregnancy outcomes in women who were diagnosed with gestational diabetes mellitus (GDM) by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria but not by the Carpenter-Coustan (CC) criteria.

Methods

A total of 8,735 Korean pregnant women were identified at two hospitals between 2014 and 2016. Among them, 2,038 women participated in the prospective cohort to investigate pregnancy outcomes. Diagnosis of GDM was made via two-step approach with 50-g glucose challenge test for screening followed by diagnostic 2-hour 75-g oral glucose tolerance test. Women were divided into three groups: non-GDM, GDM diagnosed exclusively by the IADPSG criteria, and GDM diagnosed by the CC criteria.

Results

The incidence of GDM was 2.1% according to the CC criteria, and 4.1% by the IADPSG criteria. Women diagnosed with GDM by the IADPSG criteria had a higher body mass index (22.0±3.1 kg/m² vs. 21.0±2.8 kg/m², P<0.001) and an increased risk of preeclampsia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.84 to 25.87; P=0.004) compared to non-GDM women. Compared to neonates of the non-GDM group, those of the IADPSG GDM group had an increased risk of being large for gestational age (OR, 2.39; 95% CI, 1.50 to 3.81; P<0.001), macrosomia (OR, 2.53; 95% CI, 1.26 to 5.10; P=0.009), and neonatal hypoglycemia (OR, 3.84; 95% CI, 1.01 to 14.74; P=0.049); they were also at an increased risk of requiring phototherapy (OR, 1.57; 95% CI, 1.07 to 2.31; P=0.022) compared to the non-GDM group.

Conclusion

The IADPSG criteria increased the incidence of GDM by nearly three-fold, and women diagnosed with GDM by the IADPSG criteria had an increased risk of adverse pregnancy outcomes in Korea.

Citations

Citations to this article as recorded by

Gestational diabetes mellitus and adverse maternal and perinatal outcomes in twin and singleton pregnancies: a systematic review and meta-analysis
Elena Greco, Maria Calanducci, Kypros H. Nicolaides, Eleanor V.H. Barry, Mohammed S.B. Huda, Stamatina Iliodromiti
American Journal of Obstetrics and Gynecology.2024; 230(2): 213. CrossRef
Neonatal outcomes according to different glucose threshold values in gestational diabetes: a register-based study
Kaisa Kariniemi, Marja Vääräsmäki, Tuija Männistö, Sanna Mustaniemi, Eero Kajantie, Sanna Eteläinen, Elina Keikkala, Anneli Pouta, Risto Kaaja, Johan G Eriksson, Hannele Laivuori, Mika Gissler
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The problem of diabetes mellitus in obstetrics
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Russian Bulletin of Obstetrician-Gynecologist.2024; 24(3): 25. CrossRef
2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang
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Pregnancy complications in women with pregestational and gestational diabetes mellitus
Lukas Reitzle, Christin Heidemann, Jens Baumert, Matthias Kaltheuner, Heinke Adamczewski, Andrea Icks, Christa Scheidt-Nave
Deutsches Ärzteblatt international.2023;[Epub] CrossRef
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Can Triglyceride/Glucose Index (TyG) and Triglyceride/HDL-Cholesterol Ratio (TG/HDL-c) Predict Gestational Diabetes Mellitus?
Seval YILMAZ ERGANİ, Tolgay Tuyan İLHAN, Betül TOKGÖZ, Burak BAYRAKTAR, Mevlüt BUCAK, Müjde Can İBANOĞLU, Kadriye YAKUT YÜCEL, Kadriye ERDOĞAN, Cantekin İSKENDER, Yaprak ÜSTÜN
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Clinical Care/Education
The Role of Negative Affect in the Assessment of Quality of Life among Women with Type 1 Diabetes Mellitus: Nicola R. Gawlik, Malcolm J. Bond; Diabetes Metab J. 2018;42(2):130-136. Published online November 7, 2017; DOI: https://doi.org/10.4093/dmj.2018.42.2.130

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Abstract PDF PubReader

Background

The purpose of this study is to determine the impact of negative affect (defined in terms of lack of optimism, depressogenic attributional style, and hopelessness depression) on the quality of life of women with type 1 diabetes mellitus.

Methods

Participants (n=177) completed either an online or paper questionnaire made available to members of Australian diabetes support groups. Measures of optimism, attributional style, hopelessness depression, disease-specific data, and diabetes-related quality of life were sought. Bivariate correlations informed the construction of a structural equation model.

Results

Participants were 36.3±11.3 years old, with a disease duration of 18.4±11.2 years. Age and recent glycosylated hemoglobin readings were significant contextual variables in the model. All bivariate associations involving the components of negative affect were as hypothesized. That is, poorer quality of life was associated with a greater depressogenic attributional style, higher hopelessness depression, and lower optimism. The structural equation model demonstrated significant direct effects of depressogenic attributional style and hopelessness depression on quality of life, while (lack of) optimism contributed to quality of life indirectly by way of these variables.

Conclusion

The recognition of negative affect presentations among patients, and an understanding of its relevance to diabetes-related quality of life, is a valuable tool for the practitioner.

Citations

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Menopoz dönemindeki diyabetik kadınlarda yaşanılan semptomların yaşam kalitesi parametreleri üzerindeki etkisinin incelenmesi (Prospektif Tek Grup Çalışma)
Ayşegül KOÇ, Betül ÇAKMAK, Birgül GENÇ
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Others
The Effect of 12 Weeks Aerobic, Resistance, and Combined Exercises on Omentin-1 Levels and Insulin Resistance among Type 2 Diabetic Middle-Aged Women: Zeinab AminiLari, Mohammad Fararouei, Sasan Amanat, Ehsan Sinaei, Safa Dianatinasab, Mahmood AminiLari, Nima Daneshi, Mostafa Dianatinasab; Diabetes Metab J. 2017;41(3):205-212. Published online May 18, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.3.205

6,063 View
115 Download
53 Web of Science
52 Crossref

Abstract PDF PubReader

Background

Recent studies have shown that omentin-1 derived from adipokines can affect physiological regulations and some metabolic dis-eases such as type 2 diabetes mellitus (T2DM).

Methods

The purpose of this study was to examine the impact of 12 weeks of aerobic (cycle ergometer), resistance, and combined exercises on omentin-1 level, glucose and insulin resistance indices in overweight middle age women with T2DM. In this study, 60 overweight middle age diabetic women were selected using simple random sampling and they were assigned to three groups of aerobic exercise (n=12), resistant exercise (n=12) and combined exercise (n=13), and one control group (n=15). Exercises were done in a three times per week sessions for a total of 12 weeks. Blood samples were collected before each exercise session and 24 hours after of the last session.

Results

Present study showed that fasting blood sugar decreased significantly in all intervention groups, while homeostasis model assessment of insulin resistance (HOMA-IR) decreased only in the aerobic and combined exercises groups. Furthermore, there was a significant increase in the omentin-1 level only in the combined exercise group.

Conclusion

Compared to aerobic and resistance exercises, 12 weeks of combined exercise was more efficient in improving HOMA-IR and increasing serum omentin-1 among women with T2DM.

Citations

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Obesity and Metabolic Syndrome
Importance of Lean Muscle Maintenance to Improve Insulin Resistance by Body Weight Reduction in Female Patients with Obesity: Yaeko Fukushima, Satoshi Kurose, Hiromi Shinno, Ha Cao Thu, Nana Takao, Hiromi Tsutsumi, Yutaka Kimura; Diabetes Metab J. 2016;40(2):147-153. Published online March 27, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.2.147

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Abstract PDF PubReader

Background

It has recently been suggested that skeletal muscle has an important role in insulin resistance in obesity, in addition to exercise tolerance and the fat index. The aim of this study was to identify body composition factors that contribute to improvement of insulin resistance in female patients with obesity who reduce body weight.

Methods

We studied 92 female obese patients (age 40.9±10.4 years, body mass index 33.2±4.6 kg/m²) who reduced body weight by ≥5% after an intervention program including diet, exercise therapy, and cognitive behavioral therapy. Before and after the intervention, body composition was evaluated by dual-energy X-ray absorptiometry to examine changes in skeletal muscle mass. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured as an index of insulin resistance. Cardiopulmonary exercise was also performed by all patients.

Results

There were significant improvements in body weight (–10.3%±4.5%), exercise tolerance (anaerobic threshold oxygen uptake 9.1%±18.4%, peak oxygen uptake 11.0%±14.2%), and HOMA-IR (–20.2%±38.3%). Regarding body composition, there were significant decreases in total body fat (–19.3%±9.6%), total fat-free mass (–2.7%±4.3%), and % body fat (–10.1%±7.5%), whereas % skeletal muscle significantly increased (8.9%±7.2%). In stepwise multiple linear regression analysis with change in HOMA-IR as the dependent variable, the change in % skeletal muscle was identified as an independent predictor (β=–0.280, R²=0.068, P<0.01).

Conclusion

Improvement of insulin resistance in female obese patients requires maintenance of skeletal muscle mass.

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Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women.: Jang Hyun Koh, Mi Young Lee, Soo Min Nam, Joong Kyung Sung, Pil Moon Jung, Jin Kyu Noh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2008;32(3):243-251. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.243

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Abstract PDF

BACKGROUND
Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.

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Proinflammatory Cytokines and Insulin Resistance in Nonobsese Women with High Body Fat and Low Fat Free Mass.: Young Sung Suh, In Kyu Lee, Dae Hyun Kim; Korean Diabetes J. 2007;31(2):136-143. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.136

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Abstract PDF

BACKGROUND
Adipose tissue produces and releases a variety of proinflammatory cytokines. The aim of this study was to investigate whether proinflammatory cytokines are increased and insulin resistance is presented in nonobese women with high body fat and low fat free mass. METHODS: Sixty nonobese adult premenopausal women (body mass index, BMI < 25 kg/m2) were included in this study. Body composition was determined by dual energy absoprtiometry (DXA). Fasting glucose, lipid profiles, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C reactive protein (CRP) and basal insulin were measured. RESULTS: The subjects with high body fat (> or = 30%) had higher CRP levels (P = 0.024), IL-6 levels (P = 0.008), insulin levels (P = 0.003), and homeostasis model assessment-IR (HOMA-IR) (P = 0.020) than those of the subjects with low body fat. In a subset of 32 subjects with high body fat (> or = 30%), the number of subjects with high fat free mass index (FFMI) (> or = 13.5 kg/m2) had higher atherogenic index than that of subjects with low FFMI (FFMI < 13.5 kg/m2) (P < 0.05). IL-6 was correlated with % body fat, fat mass index (FMI), and fat mass (P < 0.05). HOMA-IR was correlated with % body fat and FMI (P < 0.05). To investigate predictors of cytokines and HOMA-IR, multiple regression analysis was used. % body fat was a predictor for IL-6 and, while age and % body fat were predictors of HOMA-IR in study subjects. Conclusions: This study suggests that insulin resistance may be present in nonobese women with high body fat and low fat free mass.

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The Relationship Between the C1818T Polymorphism in Exon 4 of the klotho Gene with Fasting Glucose and Insulin Levels in Korean Women.: Ki Won Oh, Eun Joo Yun, Eun Jung Rhee, Won Young Lee, Ki Hyun Baek, Kun Ho Yoon, Moo Il Kang, Seong Gyun Kim, Cheol Young Park, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park; Korean Diabetes J. 2005;29(3):189-197. Published online May 1, 2005

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Abstract PDF: BACKGROUND
A novel gene, termed klotho has been identified as a suppressor of several aging phenotypes, and a genetic defect of klotho in mice resulted in a syndrome resembling human aging, i.e., a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis, and pulmonary emphysema. Since klotho mice also showed an abnormal glucose metabolism, we investigated the relationship between the C1818T polymorphism in exon 4 of the klotho gene and fasting glucose and insulin resistance in Korean women to observe its contribution to glucose metabolism. METHODS: The weight, height, blood pressure, fasting blood glucose, insulin, and lipid profiles were measured in 241 women(mean age, 51.2+/-7.0yr) by using the standard methods. Homeostasis model assessment(HOMA)-insulin resistance(IR), the quantitative insulin sensitivity check index(QUICKI) and HOMAbeta-cell were calculated. The genotyping of the C1818T polymorphism in exon 4 of the klotho gene was performed by allelic discrimination with using a 5' nuclease polymerase chain reaction assay. RESULTS: The allele frequencies were 0.805 for the C allele and 0.195 for the T allele, and they were in Hardy-Weinberg equilibrium(P=0.290). The mean fasting blood glucose(P= 0.005) and HOMA IR(P=0.035) were significantly higher in the T allele carriers compared with the non-carriers. After adjustment was made for age, fasting blood glucose was persistently significant(P=0.015), but the HOMA-IR became marginally significant(P=0.063). In the premenopausal women, the T allele carriers showed a higher mean fasting blood glucose(P=0.038), insulin(P=0.024), HOMA-IR(P=0.010), total cholesterol(P=0.039), and triglyceride levels(P=0.031) than in the non-carriers. After adjustment was made for age, the fasting blood glucose, insulin, HOMA-IR and triglyceride were persistently significant(P= 0.043, P=0.026, P=0.011, P=0.040). Also, the QUICKI, total cholesterol and low-density ilpo-protein cholesterol became marginally significant(P=0.073, P=0.061, P=0.098). For the postmenopausal women, the T allele carriers showed a tendency for higher mean fasting blood glucose levels(P=0.065) and lower HOMA beta-cell levels(P=0.085) than in the noncarriers. These differences became non-significant after adjustment was made for age. CONCLUSION: We observed that the C1818T polymorphism in exon 4 of the klotho gene was partly associated with glucose metabolism in Korean women. Also, these data suggest that the C1818T polymorphism is related with some cardiovascular risk factors in Korean women. The mechanism linking this gene with glucose metabolism warrants further study

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