scholarly journals Maternal and Offspring Genetic Risk of Type 2 Diabetes and Offspring Birthweight Among African Ancestry Populations

2019 ◽  
Vol 104 (11) ◽  
pp. 5032-5042
Author(s):  
Mohammad L Rahman ◽  
Deepika Shrestha ◽  
Tsegaselassie Workalemahu ◽  
Jing Wu ◽  
Chunming Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cord Blood ◽  
Genetic Risk ◽  
Adverse Pregnancy Outcome ◽  
African Ancestry ◽  
Risk Scores ◽  
C Peptide ◽  
Glucose Levels ◽  
A Genome

Abstract Objectives Maternal genetic risk of type 2 diabetes (T2D) can influence offspring birthweight through shared offspring genetic risk and by altering intrauterine glycemic status. The aim of this study was to estimate the independent effects of maternal and offspring genetic risk scores (GRSs) of T2D on offspring birthweight and the extent to which intrauterine glycemic traits mediate the effect of maternal GRSs on offspring birthweight. Design The study involved 949 mother–offspring pairs of African ancestry from the Hyperglycemia Adverse Pregnancy Outcome study. GRSs of T2D were calculated separately for mothers and offspring as the weighted sum of 91 T2D risk alleles identified in a genome-wide association study meta-analysis in African Americans. Linear regression models were fit to estimate changes in birthweight by quartiles of GRSs. Mediation analysis was implemented to estimate the direct and indirect effects of maternal GRS on offspring birthweight through cord blood C-peptide and maternal fasting and postchallenge glucose levels. Results Maternal and offspring GRSs were independently and differentially associated with offspring birthweight. Changes (95% CI) in birthweight across increasing quartiles of maternal GRSs were 0 g (reference), 83.1 g (6.5, 159.6), 103.1 g (26.0, 180.2), and 92.7 g (12.6, 172.8) (P trend = 0.041) and those of offspring GRSs were 0 (reference), −92.0 g (−169.2, −14.9), −64.9 g (−142.4, 12.6), and 2.0 g (−77.8, 81.7) (P trend = 0.032). Cord blood C-peptide mediated the effect of maternal GRS on offspring birthweight, whereas maternal postchallenge glucose levels showed additive effects with maternal GRS on birthweight. Conclusions Maternal and offspring GRSs of T2D were independently and differentially associated with offspring birthweight.

scholarly journals The frequency of Tim-3 on circulating Tfh cells was increased in type 2 diabetes mellitus patients

2020 ◽  
Vol 18 ◽  
pp. 205873922098280
Author(s):  
Shuai Guo ◽  
Xujie Yu ◽  
Limei Wang ◽  
Jing Jing ◽  
Yuanyuan Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Tfh Cells ◽  
Fasting Plasma ◽  
Healthy Donors

Type 2 diabetes mellitus (T2DM) is a chronic, low-grade inflammation disease. T follicular helper (Tfh) cells and T cell immunoglobulin and mucin domain 3 (Tim-3) are implicated in many immune diseases. This study aims to explore whether Tim-3 expression on Tfh cells is associated with T2DM progression. White blood cells (WBCs) were harvested from 30 patients with T2DM and 20 healthy donors. The abundance of circulating Tfh cells (cTfh) and the frequency of Tim-3 were analyzed by flow cytometry. Levels of fasting plasma glucose (FPG), insulin, hemoglobin A1C (HbA1C), and fasting plasma C-peptide were measured. Body mass index (BMI) and diabetes duration were also recorded. Patients with T2DM had higher numbers of cTfh cells. In addition, cTfh cells showed a negative correlation with HbA1C and diabetes duration, a positive correlation with fasting plasma C-peptide. The frequency of Tim-3 on cTfh cells was higher among T2DM patients compared with healthy donors. The in vitro experiment showed that high glucose levels increased the abundance cTfh cells but had no effect on Tim-3 expression. Our results suggest that cTfh cells and associated Tim-3 frequency may contribute to the progression of T2DM, and high glucose levels may influence cTfh cells directly.

scholarly journals Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population

Diabetologia ◽  
2010 ◽  
Vol 53 (10) ◽  
pp. 2155-2162 ◽  
Author(s):  
B. Fontaine-Bisson ◽  
◽  
F. Renström ◽  
O. Rolandsson ◽  
F. Payne ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Risk ◽  
Risk Scores ◽  
Discriminative Power ◽  
Swedish Population ◽  
Genetic Risk Scores

scholarly journals SNP-Based Genetic Risk Score Modeling Suggests No Increased Genetic Susceptibility of the Roma Population to Type 2 Diabetes Mellitus

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 942 ◽  
Author(s):  
Nardos Abebe Werissa ◽  
Peter Piko ◽  
Szilvia Fiatal ◽  
Zsigmond Kosa ◽  
Janos Sandor ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
General Population ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Unhealthy Lifestyle ◽  
Roma Population

Background: In a previous survey, an elevated fasting glucose level (FG) and/or known type 2 diabetes mellitus (T2DM) were significantly more frequent in the Roma population than in the Hungarian general population. We assessed whether the distribution of 16 single nucleotide polymorphisms (SNPs) with unequivocal effects on the development of T2DM contributes to this higher prevalence. Methods: Genetic risk scores, unweighted (GRS) and weighted (wGRS), were computed and compared between the study populations. Associations between GRSs and FG levels and T2DM status were investigated in separate and combined study populations. Results: The Hungarian general population carried a greater genetic risk for the development of T2DM (GRSGeneral = 15.38 ± 2.70 vs. GRSRoma = 14.80 ± 2.68, p < 0.001; wGRSGeneral = 1.41 ± 0.32 vs. wGRSRoma = 1.36 ± 0.31, p < 0.001). In the combined population models, GRSs and wGRSs showed significant associations with elevated FG (p < 0.001) and T2DM (p < 0.001) after adjusting for ethnicity, age, sex, body mass index (BMI), high-density Lipoprotein Cholesterol (HDL-C), and triglyceride (TG). In these models, the effect of ethnicity was relatively strong on both outcomes (FG levels: βethnicity = 0.918, p < 0.001; T2DM status: ORethnicity = 2.484, p < 0.001). Conclusions: The higher prevalence of elevated FG and/or T2DM among Roma does not seem to be directly linked to their increased genetic load but rather to their environmental/cultural attributes. Interventions targeting T2DM prevention among Roma should focus on harmful environmental exposures related to their unhealthy lifestyle.

Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

2014 ◽  
Vol 307 (7) ◽  
pp. R862-R868 ◽  
Author(s):  
Jennifer P. Richards ◽  
Gina L. C. Yosten ◽  
Grant R. Kolar ◽  
Cory W. Jones ◽  
Alan H. Stephenson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Tissue Oxygenation ◽  
Atp Release ◽  
Peripheral Vascular ◽  
Healthy Human ◽  
C Peptide ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Healthy Humans

ATP release from erythrocytes in response to reduced oxygen (O2) tension stimulates local vasodilation, enabling these cells to direct perfusion to areas in skeletal muscle in need of O2. Erythrocytes of humans with type 2 diabetes do not release ATP in response to low O2. Both C-peptide and insulin individually inhibit low O2-induced ATP release from healthy human erythrocytes, yet when coadministered at physiological concentrations and ratios, no inhibition is seen. Here, we determined: that 1) erythrocytes of healthy humans and humans with type 2 diabetes possess a C-peptide receptor (GPR146), 2) the combination of C-peptide and insulin at physiological ratios rescues low O2-induced ATP release from erythrocytes of humans with type 2 diabetes, 3) residual C-peptide levels reported in humans with type 2 diabetes are not adequate to rescue low O2-induced ATP release in the presence of 1 nM insulin, and 4) the effects of C-peptide and insulin are neither altered by increased glucose levels nor explained by changes in erythrocyte deformability. These results suggest that the addition of C-peptide to the treatment regimen for type 2 diabetes could have beneficial effects on tissue oxygenation, which would help to ameliorate the concomitant peripheral vascular disease.

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