scholarly journals Association of single nucleotide polymorphisms with insulin secretion, insulin sensitivity, and diabetes in women with a history of gestational diabetes mellitus

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rashmi B. Prasad ◽  
Karl Kristensen ◽  
Anastasia Katsarou ◽  
Nael Shaat
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Disposition Index ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Impaired Insulin ◽  
History Of

Abstract Background This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). Methods Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity. Conclusions This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.

scholarly journals Association of Single Nucleotide Polymorphisms With Insulin Secretion, Insulin Sensitivity, and Diabetes in Women With a History of Gestational Diabetes Mellitus

2021 ◽  
Author(s):  
Rashmi Prasad ◽  
Karl Kristensen ◽  
Anastasia Katsarou ◽  
Nael Shaat
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Disposition Index ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Impaired Insulin ◽  
History Of

Abstract Aims: This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM).Methods: Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results: The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = -0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), was associated with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). All analyses were adjusted for age, body mass index, and ethnicity.Conclusions: This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.

Insulin resistance and impaired insulin secretion in subjects with histories of gestational diabetes mellitus

Diabetes ◽  
1985 ◽  
Vol 34 (9) ◽  
pp. 861-869 ◽  
Author(s):  
W. K. Ward ◽  
C. L. Johnston ◽  
J. C. Beard ◽  
T. J. Benedetti ◽  
J. B. Halter ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

scholarly journals Leaner Women with Impaired Insulin Secretion Accounts for about 40% of Gestational Diabetes Mellitus in Japan

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Seishi Furukawa ◽  
Yoichi Kobayashi
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Gestational Diabetes Mellitus ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

Aim. To identify the involvement of leanness and impaired insulin secretion with Japanese gestational diabetes mellitus (GDM). Method. A cross-sectional study was conducted comprising 219 at-risk pregnant women who underwent a 75g glucose tolerance test at a single institute in Tokyo, Japan. We identified GDM and normal glucose tolerance (NGT). The cut-off value of the homeostasis model assessment insulin resistance (HOMA-IR) for detecting GDM was determined. The GDM group was divided into subgroups according to insulin resistance based on the cut-off value of HOMA-IR. We compared the prepregnancy body mass index (BMI) and homeostasis model assessment of β-cell function (HOMA-β) between the group comprising low insulin resistance (LIR) and the group comprising high insulin resistance (HIR). Results. Seventy GDM cases and 149 NGT cases were identified. By using receiver operating characteristic curve analysis, the HOMA-IR cut-off value was determined to be 1.41. Twenty-five GDM cases (36%) were classified as LIR and forty-five GDM cases (64%) were classified as HIR. The background including indications for having 75gOGTT and the gestational age having 75gOGTT did not differ between groups. The BMI of the LIR group was significantly lower than that of the HIR group (20.9±2.8 vs. 24.4 ± 5.5, p<0.01), and the HOMA-β of the LIR group was significantly lower than that of the HIR group (95.5±30.3 vs. 146.0±70.1, p<0.01). A positive linear correlation was found between BMI and HOMA-β in cases of GDM (r=0.27, p=0.02). Conclusion. Leanness with impaired insulin secretion is deeply involved in Japanese gestational diabetes mellitus.

Insulin Resistance and Impaired Insulin Secretion in Subjects with Histories of Gestational Diabetes Mellitus

Diabetes ◽  
1985 ◽  
Vol 34 (9) ◽  
pp. 861-869 ◽  
Author(s):  
W. K. Ward ◽  
C. L. W. Johnston ◽  
J. C. Beard ◽  
T. J. Benedetti ◽  
J. B. Halter ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Secretion ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Impaired Insulin Secretion ◽  
Impaired Insulin

scholarly journals Single Nucleotide Polymorphisms in CDKAL1 Gene Are Associated with Risk of Gestational Diabetes Mellitus in Chinese Population

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Keke Wang ◽  
Qiong Chen ◽  
Yongliang Feng ◽  
Hailan Yang ◽  
Weiwei Wu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Health Concern ◽  
Nucleotide Polymorphisms ◽  
Family History Of Diabetes ◽  
Gene Level ◽  
Risk Snps ◽  
History Of ◽  
Nested Case Control

Gestational diabetes mellitus (GDM) is a growing public health concern for many reasons, and its etiology remains unclear. Due to the similarity of its pathophysiology with type 2 diabetes (T2DM), we evaluated the relationship between published T2DM susceptibility genes and the risk of GDM. A total of 303 SNPs from genes including IRS1, IGF2BP2, CDKAL1, GCK, TCF7L2, KCNQ1, and KCNJ11 and the risk of GDM were examined in a nested case-control study with 321 GDM cases and 316 controls. The odds ratios (ORs) and their 95% confidence interval (95% CI) were estimated by unconditional logistical regression as a measure of the associations between genotypes and GDM in additive, recessive, dominant, and codominant models adjusting for maternal age, maternal BMI, parity, and family history of diabetes. At the gene level, CDKAL1 was associated with GDM risk. SNPs in the CDKAL1 gene including rs4712527, rs7748720, rs9350276, and rs6938256 were associated with reduced GDM risk. However, SNPs including rs9295478, rs6935599, and rs7747752 were associated with elevated GDM risk. After adjusting for multiple comparisons, rs9295478 and rs6935599 were still significant across the additive, recessive, and codominant models; rs7748720 and rs6938256 were significant in dominant and codominant models; and rs4712527 was only significant in the codominant model. Our study provides evidence for an association between the CDKAL1 gene and risk of GDM. However, its role in the GDM pathogenesis still needs to be verified by further studies.

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