Increased circulating cytokine levels in African American women with obesity and elevated HbA1c.
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ABSTRACT:
SUBMITTER: Williams A
PROVIDER: S-EPMC7058975 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose:Type 2 diabetes is heterogeneous disease characterized by several conditions including hyperglycemia. It is estimated that over 350 million people worldwide are suffering from type 2 diabetes and this number is expected to rise. According to the CDC, African Americans were observed to have a 40% higher incidence of diabetes compared to European Americans. Epigenetic modulating mechanisms such as microRNAs (miRNAs), have recently been established as a massive regulatory machine in metabolic syndrome, obesity and type 2 diabetes. In the present study, we aimed to investigate the serum levels of circulating miRNA 17 (miR-17) of obese, African American women with elevated HbA1c. Methods:We investigated miR-17 serum levels using qPCR. Then we used Pairwise Pearson Correlation Test to determine the relationship between clinical metabolic parameters and miR-17 serum levels. Results:The results indicated that participants with elevated HbA1c exhibited a down regulation of serum miR-17 levels compared to participants with normal HbA1c. MiR-17 was also correlated with serum calcium in participants with normal HbA1c. Conclusions:The results suggest that serum miR-17 is involved in the regulation of glucose and calcium homeostasis, which may contribute to the development of type 2 diabetes.
| S-EPMC6582114 | biostudies-literature
Project description:Circulating insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNP) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians, 631 ng/mL; 95% confidence interval, 398-864; African Americans, 897 ng/mL; 95% confidence interval, 656-1,138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than reference diplotypes with the CG genotype, whereas IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (-202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with >or=5% differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with >or=10% differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels.
| S-EPMC2896274 | biostudies-literature
Project description:IntroductionAlthough prior studies have shown that smoking reduces preeclampsia risk, the relationship between nicotine level and preeclampsia risk is not known. Our objective was to study the effects of smoking on the incidence of preeclampsia in African-American women using cotinine, a quantitative marker of nicotine.MethodsWe performed a secondary analysis of data collected prospectively in Project District of Columbia Healthy Outcomes of Pregnancy Education. Our study included 724 African-American women. Self-reported smoking, cotinine levels, and pregnancy outcomes were examined.ResultsSome 18% of participants were smokers. Women with salivary cotinine levels greater than 200 ng/ml had infants with lower birth weights and a higher incidence of small-for-gestational-age infants than women with cotinine levels of 200 ng/ml or less. Exact logistic regression analysis revealed that women with salivary cotinine levels greater than 200 ng/ml had a significantly lower incidence of preeclampsia, compared with women with cotinine levels of 200 ng/ml or less, in unadjusted analysis (odds ratio [OR] = 0.16, 95% CI = 0-0.90). After controlling for age, parity, and medical comorbidities, the trend was observed, but the effect was no longer significant (adjusted odds ratio [AOR] = 0.19, 95% CI = 0-1.11). We found no significant differences in preeclampsia rates using lower cutoffs of cotinine exposure. We did not observe a decrease in preeclampsia incidence at low or moderate cotinine levels.DiscussionWomen with the highest cotinine levels may have a decreased risk for preeclampsia, although this effect was not significant after controlling for other risk factors.
| S-EPMC2688602 | biostudies-literature
Project description:Obesity-driven Type 2 diabetes (T2D) is a systemic inflammatory condition associated with cardiovascular disease. However, plasma cytokines and tissue inflammation that discriminate T2D risk in African American women with obese phenotypes are not well understood. We analyzed 64 circulating cytokines and chemokines in plasma of 120 African American women enrolled in the Black Women's Health Study. We used regression analysis to identify cytokines and chemokines associated with obesity, co-morbid T2D and hypertension, and compared results to obese women without these co-morbidities, as well as to lean women without the co-morbidities. We then used hierarchical clustering to generate inflammation signatures by combining the effects of identified cytokines and chemokines and summarized the signatures using an inflammation score. The analyses revealed six distinct signatures of sixteen cytokines/chemokines (P = 0.05) that differed significantly by prevalence of T2D (P = 0.004), obesity (P = 0.0231) and overall inflammation score (P < E-12). Signatures were validated in two independent cohorts of African American women with obesity: thirty nine subjects with no metabolic complications or with T2D and hypertension; and thirteen breast reduction surgical patients. The signatures in the validation cohorts closely resembled the distributions in the discovery cohort. We find that blood-based cytokine profiles usefully associate inflammation with T2D risks in vulnerable subjects, and should be combined with metabolism and obesity counselling for personalized risk assessment.
| S-EPMC5940209 | biostudies-literature
Project description:ContextSerum estradiol levels are significantly higher across the menstrual cycle in African American (AAW) compared with Caucasian women (CW) in the presence of similar FSH levels, yet the mechanism underlying this disparity is unknown.ObjectiveThe objective of the study was to determine whether higher estradiol levels in AAW are due to increased granulosa cell aromatase mRNA expression and activity.DesignThe design of the study included daily blood sampling and dominant follicle aspirations at an academic medical center during a natural menstrual cycle.SubjectsHealthy, normal cycling AAW (n = 15) and CW (n = 14) aged 19-34 years participated in the study.Main outcome measuresHormone levels in peripheral blood and follicular fluid (FF) aspirates and aromatase and FSH receptor mRNA expression in granulosa cells were measured.ResultsAAW had higher FF estradiol [1713.0 (1144.5-2032.5) vs 994.5 (647.3-1426.5) ng/mL; median (interquartile range); P < .001] and estrone [76.9 (36.6-173.4) vs 28.8 (22.5-42.1) ng/mL; P < .001] levels than CW, independent of follicle size. AAW also had lower FF androstenedione to estrone (7 ± 1.8 vs 15.8 ± 4.1; mean ± SE; P = .04) and T to estradiol (0.01 ± 0.002 vs 0.02 ± 0.005; P = .03) ratios, indicating enhanced ovarian aromatase activity. There was a 5-fold increase in granulosa cell aromatase mRNA expression in AAW compared with CW (P < .001) with no difference in expression of FSH receptor. FSH, inhibin A, inhibin B, and AMH levels were not different in AAW and CW.ConclusionsIncreased ovarian aromatase mRNA expression, higher FF estradiol levels, and decreased FF androgen to estrogen ratios in AAW compared with CW provide compelling evidence that racial differences in ovarian aromatase activity contribute to higher levels of estradiol in AAW across the menstrual cycle. The absence of differences in FSH, FSH receptor expression, and AMH suggest that population-specific genetic variation in CYP19, the gene encoding aromatase, or in factors affecting its expression should be sought.
| S-EPMC3973772 | biostudies-literature
Project description:ObjectiveThe principal objective of this investigation was to identify novel cytokine associations with BMI and type 2 diabetes (T2D).MethodsCytokines were profiled from African American women with obesity who donated plasma to the Komen Tissue Bank. Multiplex bead arrays of analytes were used to quantify 88 cytokines and chemokines in association with clinical diagnoses of metabolic health. Regression models were generated after elimination of outliers.ResultsAmong women with obesity, T2D was associated with breast adipocyte hypertrophy and with six plasma analytes, including four chemokines (chemokine [C-C motif] ligand 2, chemokine [C-C motif] ligand 16, chemokine [C-X-C motif] ligand 1, and chemokine [C-X-C motif] ligand 16) and two growth factors (interleukin 2 and epidermal growth factor). In addition, three analytes were associated with obesity independently of diabetes: interleukin 4, soluble CD40 ligand, and chemokine (C-C motif) ligand 3.ConclusionsProfiling of inflammatory cytokines combined with measures of BMI may produce a more personalized risk assessment for obesity-associated disease in African American women.
| S-EPMC5669048 | biostudies-literature
Project description:Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk.
| S-EPMC6018807 | biostudies-literature
Project description:Preeclampsia occurs more frequently in women of African ancestry. The cause of this hypertensive complication is unclear, but placental oxidative stress may play a role. Because mitochondria are the major sites of oxidative phosphorylation, we hypothesized that placentas of preeclamptic pregnancies harbor mitochondrial DNA (mtDNA) mutations. Next-generation sequencing of placental mtDNA in African American preeclamptics (N = 30) and controls (N = 38) from Chicago revealed significant excesses in preeclamptics of nonsynonymous substitutions in protein-coding genes and mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene and an increase in the substitution rate (P = .0001). Moreover, 88% of preeclamptics and 53% of controls carried at least one nonsynonymous substitution (P = .005; odds ratio [OR] = 6.36, 95% confidence interval [CI]: 1.5-39.1). These results were not replicated in a sample of African American preeclamptics (N = 162) and controls (N = 171) from Detroit. Differences in study design and heterogeneity may account for this lack of replication. Nonsynonymous substitutions in mtDNA may be risk factors for preeclampsia in some African American women, but additional studies are required to establish this relationship.
| S-EPMC4046444 | biostudies-literature
Project description:Increased abdominal obesity is associated with increased cardiovascular risk, especially in African American women. The adipocyte is documented to produce a number of inflammatory factors including the hormone aldosterone. There are very few data documenting aldosterone production from adipocytes of postmenopausal women as well as data demonstrating the effects of angiotensin receptor blockade (ARB) on its production in predominately African American women. The authors hypothesize that increased central adipocyte mass in obese postmenopausal women contributes to increased production of aldosterone that is suppressed with the ARB azilsartan medoxomil. The authors tested this hypothesis in a double-blind, placebo-controlled pilot study of 34 hypertensive postmenopausal women (mean age 57.5±7.5 years), 91% of whom were African American. Patients had a mean 24-hour ambulatory systolic blood pressure of 127±13 mm Hg off any blocker of the renin-angiotensin system but while taking other antihypertensive medications. The authors further validated aldosterone production in a nested cohort of women using fat cells from a fat pad biopsy. Azilsartan reduced 24-hour urinary aldosterone by 47.3% from baseline (P=.03), with between-groups differences in urine aldosterone of -5.3±52.3% placebo vs -47.3±32.9% azilsartan (P=.07) at 6 months. An adrenal cell line treated with adipocyte-conditioned media from subcutaneous abdominal adipocytes of postmenopausal women (n=3) showed an increase in aldosterone production blocked by an ARB (1948±1297 pg/mL fat alone vs 894±438 pg/mL fat + ARB; P=.022). The authors conclude that aldosterone is produced from subcutaneous adipocytes of obese postmenopausal women. Moreover, use of an ARB significantly reduces aldosterone production within 6 months of use in these women as well as in cells exposed to their adipocytes.
| S-EPMC8031884 | biostudies-literature
Project description:BACKGROUND:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target. OBJECTIVE:We compared serum PCSK9 levels in young adults, with and without type 2 diabetes. SUBJECTS AND METHODS:Cross-sectional analysis was conducted in a cohort, aged 15 to 26?years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects. Correlative analyses were conducted to determine significant covariates of PCSK9 by group and sex, and multivariate linear regression models were used to study the independent determinants of PCSK9. RESULTS:In females, PCSK9 levels were significantly increased in the obese and type 2 diabetes subjects relative to the lean controls (P?<?.01). Moreover, PCSK9 was positively correlated with multiple metabolic parameters in females: body mass index, systolic blood pressure, fasting glucose, fasting insulin, and C-reactive protein levels (P???.02). In males, PCSK9 levels were decreased overall compared with females (P?=?.03), and did not differ between the lean, obese, or type 2 diabetes groups. CONCLUSIONS:Obesity and type 2 diabetes were associated with significantly higher levels of PCSK9 in young women, but not in young men. These data suggest that sex could modify the effects of obesity and diabetes on PCSK9 in young adults.
| S-EPMC5513789 | biostudies-literature