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  • The Endocrine Society  (8)
  • 1
    Online Resource
    Online Resource
    High Plasma Retinol Binding Protein-4 and Low Plasma Adiponectin Concentrations Are Associated with Severity of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus
    The Endocrine Society ; 2008
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 8 ( 2008-08-01), p. 3142-3148
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 93, No. 8 ( 2008-08-01), p. 3142-3148
    Abstract: Context: Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. Objective: We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM. Design, Setting, Patients, and Main Outcome Measures: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8). Results: Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. Conclusions: The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2007-1755
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 2026217-6
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  • 2
    Online Resource
    Online Resource
    Clinical and Genetic Risk Factors for Type 2 Diabetes at Early or Late Post Partum After Gestational Diabetes Mellitus
    The Endocrine Society ; 2013
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 98, No. 4 ( 2013-04), p. E744-E752
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 98, No. 4 ( 2013-04), p. E744-E752
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2012-3324
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2013
    detail.hit.zdb_id: 2026217-6
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  • 3
    Online Resource
    Online Resource
    Weight Gain and Progression to Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus
    The Endocrine Society ; 2015
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 100, No. 9 ( 2015-09), p. 3548-3555
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 100, No. 9 ( 2015-09), p. 3548-3555
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/JC.2015-1113
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2015
    detail.hit.zdb_id: 2026217-6
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  • 4
    Online Resource
    Online Resource
    Estimated Association Between Cytokines and the Progression to Diabetes: 10-year Follow-Up From a Community-Based Cohort
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 3 ( 2020-03-01), p. e381-e389
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 3 ( 2020-03-01), p. e381-e389
    Abstract: The long-term association between multiple cytokines and progression to diabetes is still uncertain. Objective To identify which cytokines could predict progression to prediabetes and type 2 diabetes over 10 years. Methods The study included 912 participants aged 40 to 69 years at baseline from the Ansung cohort, part of the Korea Genome Epidemiology Study. At baseline, a 75-g oral glucose tolerance test and 8 cytokines were measured: plasminogen activator inhibitor 1 (PAI-1), resistin, interleukin 6, leptin, monocyte chemoattractant protein 1, tumor necrosis factor alpha, retinol binding protein 4 (RBP4), and adiponectin. People with normal glucose tolerance (NGT, n = 241) and prediabetes (n = 330) were followed-up biennially for 10 years. Multinomial logistic regression analysis was used to evaluate the predictability of cytokines on the new-onset prediabetes and type 2 diabetes. Results At 10 years, 38 (15.8%) and 82 (34.0%) of those with NGT had converted to prediabetes and type 2 diabetes, respectively. Of those with prediabetes, 228 (69.1%) had converted to type 2 diabetes. In people with NGT or prediabetes at baseline, the highest tertile of RBP4 was associated with a 5.48-fold and 2.43-fold higher risk of progression to type 2 diabetes, respectively. The odds for converting from NGT to prediabetes in the highest tertile of PAI-1 and the lowest tertile of adiponectin were 3.23 and 3.37, respectively. In people with prediabetes at baseline, those in the highest tertile of resistin were 2.94 time more likely to develop type 2 diabetes (all P & lt; 0.05). Conclusions In this 10-year prospective study, NGT with higher serum RBP4 and PAI-1, and with lower adiponectin were associated with new-onset prediabetes and type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgz171
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 5
    Online Resource
    Online Resource
    DNA Methylation Changes Associated With Type 2 Diabetes and Diabetic Kidney Disease in an East Asian Population
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 10 ( 2021-09-27), p. e3837-e3851
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 10 ( 2021-09-27), p. e3837-e3851
    Abstract: There is a growing body of evidence that epigenetic changes including DNA methylation influence the risk of type 2 diabetes (T2D) and its microvascular complications. Objective We conducted a methylome-wide association study (MWAS) to identify differentially methylated sites (DMSs) of T2D and diabetic kidney disease (DKD) in a Korean population. Methods We performed an MWAS in 232 participants with T2D and 197 nondiabetic controls with the Illumina EPIC bead chip using peripheral blood leukocytes. The T2D group was subdivided into 87 DKD patients and 80 non-DKD controls. An additional 819 individuals from 2 population-based cohorts were used to investigate the association of identified DMSs with quantitative metabolic phenotypes. A mendelian randomization (MR) approach was applied to evaluate the causal effect of metabolic phenotypes on identified DMSs. Results We identified 8 DMSs (each at BMP8A, NBPF20, STX18, ZNF365, CPT1A, and TRIM37, and 2 at TXNIP) that were significantly associated with the risk of T2D (P  & lt; 9.0 × 10–8), including 3 that were previously known (DMSs in TXNIP and CPT1A). We also identified 3 DMSs (in COMMD1, TMOD1, and FHOD1) associated with DKD. With our limited sample size, we were not able to observe a significant overlap between DMSs of T2D and DKD. DMSs in TXNIP and CTP1A were associated with fasting glucose and glycated hemoglobin A1c. In MR analysis, fasting glucose was causally associated with DMS in CPT1A. Conclusion In an East Asian population, we identified 8 DMSs, including 5 novel CpG loci, associated with T2D and 3 DMSs associated with DKD at methylome-wide statistical significance.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgab488
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 6
    Online Resource
    Online Resource
    Sequencing Cell-free Fetal DNA in Pregnant Women With GCK -MODY
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 9 ( 2021-08-18), p. 2678-2689
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 9 ( 2021-08-18), p. 2678-2689
    Abstract: Individuals with monogenic diabetes due to inactivating glucokinase (GCK) variants typically do not require treatment, except potentially during pregnancy. In pregnancy, fetal GCK genotype determines whether treatment is indicated, but noninvasive methods are not clinically available. Objective This work aims to develop a method to determine fetal GCK genotype noninvasively using maternal cell-free fetal DNA. Methods This was a proof-of-concept study involving 3 pregnant women with a causal GCK variant that used information from 1) massive parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) the paternal genotypes to estimate relative haplotype dosage of the pathogenic variant-linked haplotype. Statistical testing of variant inheritance was performed using a sequential probability ratio test (SPRT). Results In each of the 3 cases, plasma cell-free DNA was extracted once between gestational weeks 24 and 36. The fetal fraction of cell-free DNA ranged from 21.8% to 23.0%. Paternal homozygous alleles that were identical to the maternal GCK variant-linked allele were not overrepresented in the cell-free DNA. Paternal homozygous alleles that were identical to the maternal wild-type–linked allele were significantly overrepresented. Based on the SPRT, we predicted that all 3 cases did not inherit the GCK variant. Postnatal infant genotyping confirmed our prediction in each case. Conclusion We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgab265
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 7
    Online Resource
    Online Resource
    Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population
    The Endocrine Society ; 2019
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 104, No. 9 ( 2019-09-01), p. 4188-4198
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 9 ( 2019-09-01), p. 4188-4198
    Abstract: Monogenic diabetes is a specific type of diabetes in which precision medicine could be applied. In this study, we used targeted panel sequencing to investigate pathogenic variants in Korean patients with clinically suspected monogenic diabetes. Methods The eligibility criteria for inclusion were patients with nontype 1 diabetes with age at onset ≤30 years and body mass index (BMI) ≤30 kg/m2. Among the 2090 patients with nontype 1 diabetes, 109 had suspected monogenic diabetes and underwent genetic testing. We analyzed 30 monogenic diabetes genes using targeted panel sequencing. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Results Among the 109 patients with suspected monogenic diabetes, 23 patients (21.1%) harbored pathogenic/likely pathogenic variants. A total of 14 pathogenic/likely pathogenic variants of common maturity-onset diabetes of the young (MODY) genes were identified in GCK, HNF1A, HNF4A, and HNF1B. Other pathogenic/likely pathogenic variants were identified in WFS1, INS, ABCC8, and FOXP3. The mitochondrial DNA 3243A 〉 G variant was identified in five participants. Patients with pathogenic/likely pathogenic variants had a significantly higher MODY probability, a lower BMI, and a lower C-peptide level than those without pathogenic/likely pathogenic variants (P = 0.007, P = 0.001, and P = 0.012, respectively). Conclusions Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 patients (21.1%) with suspected monogenic diabetes. Lower BMI, higher MODY probability, and lower C-peptide level were characteristics of these participants.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2018-02397
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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  • 8
    Online Resource
    Online Resource
    RF17 | P715 Contribution of Low Muscle Mass and Genetic Factors in NAFLD and Liver Cirrhosis
    The Endocrine Society ; 2022
    In:  Journal of the Endocrine Society Vol. 6, No. Supplement_1 ( 2022-11-01), p. A461-A462
    Details
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 6, No. Supplement_1 ( 2022-11-01), p. A461-A462
    Abstract: Both sarcopenia and genetic risk factors are important risk factors for non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the independent effects of low muscle mass and genetic risk factors in the development of NAFLD and liver cirrhosis (LC) in the Korean population. Method: A prospective community-based cohort consisted of adults with age 40–70 years were followed-up biennially from 2001–2002 to 2017–2018. NAFLD was defined as hepatic steatosis index of ≥36, and liver cirrhosis (LC) was defined as a fibrosis-4 index score of ≥1.3. The subjects were divided into four groups according to body mass index (BMI)-adjusted muscle mass. Cox proportional hazards models incorporating age, sex, BMI≥ 25 kg/m2, metabolic syndrome, and PNPLA3, and TM6SF2 risk alleles were used to assess the independent determinants for the incident NAFLD and development of LC among individuals with NAFLD at baseline. Results Among the 4,038 participants without NAFLD at baseline, 920 (22.8%) developed NAFLD during the follow-up. Both the TM6SF2 risk alleles (hazard ratio [HR]. 1.19, [95% confidence interval (CI), 1.00–1.40] , P=0.044) and muscle mass index quartiles (Q) (HR per 1 Q, 1.18, 95% CI, 1.11–1.27, P & lt;0.001) were associated with development of NAFLD in the fully adjusted model. Of the 1,442 patients with NAFLD at baseline, LC was eventually confirmed in 552 (38.3%) patients. Only the PNPLA3 risk variant, but not the TM6SF2 genotype nor muscle mass index, was an independent risk factor for developing LC among NAFLD subjects (HR 1.22, 95% CI 1.08–1.38, P=0.001) Conclusion Both the lower muscle mass index and genetic risk variants are important contributors in the development of NAFLD. In patients already diagnosed with NALFD however, PNPLA3 conferred a greater risk for the progression to LC than lower muscle mass. Presentation: No date and time listed
    Type of Medium: Online Resource
    ISSN: 2472-1972
    URL: Article
    DOI: 10.1210/jendso/bvac150.960
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2881023-5
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