BACKGROUND: Certain endocrine-disrupting chemicals (EDCs) are widespread in consumer products and may alter glucose metabolism. However, the impact of EDC exposures on glucose and insulin regulation during pregnancy is incompletely understood, despite potential adverse consequences for maternal and infant health. We estimated associations between 37 urinary biomarkers of EDCs and glucose-insulin traits among pregnant women.
METHODS: Seventeen phthalate or phthalate substitute metabolites, six environmental phenols, four parabens, and ten organophosphate ester metabolites were quantified in mid-pregnancy urine from 298 participants in the Healthy Start Study. Fasting blood glucose, insulin, and hemoglobin A1c were assessed concurrently, and Homeostasis Model Assessment 2-Insulin Resistance (HOMA2-IR) was calculated. Gestational diabetes diagnoses and screening results were obtained from medical records for a subset of participants. We estimated associations between each EDC and outcome separately using linear and robust Poisson regression models and analyzed EDC mixture effects.
RESULTS: The EDC mixture was positively associated with glucose, insulin, and HOMA2-IR, although overall associations were attenuated after adjustment for maternal BMI. Two mixture approaches identified di(2-ethylhexyl) phthalate (DEHP) metabolites as top contributors to the mixture\'s positive associations. In single-pollutant models, DEHP metabolites were positively associated with fasting glucose, fasting insulin, and HOMA2-IR even after adjustment for maternal BMI. For example, each interquartile range increase in log2-transformed mono(2-ethyl-5-oxohexyl) phthalate was associated with 2.4 mg/dL (95% confidence interval (CI): 1.1, 3.6) higher fasting glucose, 11.8% (95%CI: 3.6, 20.5) higher fasting insulin, and 12.3% (95%CI: 4.2, 21.1) higher HOMA2-IR. Few EDCs were associated with hemoglobin A1c or with a combined outcome of impaired glucose tolerance or gestational diabetes.
CONCLUSIONS: Exposures to phthalates and particularly DEHP during pregnancy are associated with altered glucose-insulin regulation. Disruptions in maternal glucose metabolism during pregnancy may contribute to adverse pregnancy outcomes including gestational diabetes and fetal macrosomia, and associated long-term consequences for maternal and child health.

Dietary intake of live microbes may benefit human health, but less is known about the role in insulin resistance. This study was developed with the goal of evaluating potential relationships between IR and dietary live microbes. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged to collect data from 6,333 subjects 18 + years of age. The Sanders system for the classification of dietary live microbe intake (containing Low (< 104 CFU/g), Medium (104-107 CFU/g), or High (> 107 CFU/g) levels of live microbes) was then used to separate these patients into three groups (low, medium, or high). Fasting blood glucose and insulin levels were used to approximate IR based on the homeostasis model of insulin resistance (HOMA-IR). Weighted linear regressions were used to assess the relationship between IR and live microbe intake. After fully adjusting for confounding factors, subjects in the groups exhibiting medium and high levels of live microbe intake exhibited HOMA-IR scores that were below those of subjects in the low group. The relationship between live microbe intake and HOMA-IR scores was also potentially impacted by ethnicity. In summary, a negative correlation was detected between dietary live microbe intake and HOMA-IR values.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported.
METHODS: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated.
RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment.
CONCLUSIONS: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

BACKGROUND: Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain.
METHODS: We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999-2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors.
RESULTS: In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L.
CONCLUSIONS: HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.

UNASSIGNED: Antenatal iron deficiency and anaemia are associated with gestational hypertension and diabetes mellitus, but so are elevated iron stores and haemoglobin. In South Africa, pregnant women receive routine iron supplementation regardless of iron status.
UNASSIGNED: This study aimed to assess associations of antenatal iron status and anaemia with blood pressure in pregnant women in urban South Africa. Secondary to this, associations with heart rate, fasting glucose and glucose tolerance were also investigated.
UNASSIGNED: Johannesburg, South Africa.
UNASSIGNED: A total of 250 pregnant women, aged 27 (24-32) years, were recruited using consecutive sampling. The authors measured biomarkers of iron status and anaemia at < 18 and ± 22 weeks\', blood pressure and heart rate at ± 36 weeks\', and fasting glucose and glucose tolerance between 24 and 28 weeks\' gestation. Associations were determined using multivariable regression models adjusted for confounders.
UNASSIGNED: The odds of prehypertension in late pregnancy among women with anaemia at ± 22 weeks\' gestation were three times higher than among women without anaemia (odds ratio [OR]: 3.01, 95% confidence interval [CI]: 1.22, 7.42). Participants with anaemia at ± 22 weeks\' gestation had 2.15 times higher odds of having elevated mean arterial pressure than women without anaemia (OR: 2.15, 95% CI: 1.01, 4.60).
UNASSIGNED: Anaemia at mid-pregnancy could be a predictor of hypertensive disorders in pregnancy. The cause of antenatal anaemia may need further investigation apart from iron deficiency. The effective management of anaemia in pregnant women living in urban South Africa remains a challenge.
UNASSIGNED: This study provides evidence about the health impact of pregnant women regarding antenatal supplementation practices in South Africa.

BACKGROUND: We conducted a systematic review and meta-analysis to examine the effect of dietary intake of cocoa on anthropometric measurements, lipid and glycemic profiles, and blood pressure levels in adults, with and without comorbidities.
METHODS: The databases used were MEDLINE (PubMed), EMBASE, Web of Science, Cochrane, LILACS, and SciELO. The eligible studies were randomized clinical trials (RCTs) involving adults undergoing cocoa consumption (cocoa extract or ≥70% cocoa dark chocolate) for ≥4 weeks that evaluated at least one of the following markers: body weight, body mass index (BMI), waist/abdominal circumference, total cholesterol, LDL-c, triglycerides, HDL-c, blood glucose, glycated hemoglobin (HbA1c), and systolic and diastolic blood pressure (SBP/DBP).
RESULTS: Thirty-one studies were included, totaling 1986 participants. Cocoa consumption showed no effects on body weight, BMI, waist circumference, triglycerides, HDL-c and HbA1c. Yet, there was a reduction in total cholesterol (-8.35 mg/dL, 95% CI -14.01; -2.69 mg/dL), LDL-c (-9.47 mg/dL, 95% CI -13.75; -5.20 mg/dL), fasting blood glucose (-4.91 mg/dL, 95% CI -8.29; -1.52 mg/dL), SBP (-2.52 mmHg, 95% CI -4.17; -0.88 mmHg), and DBP (-1.58 mmHg, 95% CI -2.54; -0.62 mmHg).
CONCLUSIONS: The consumption of cocoa showed protective effects on major cardiometabolic risk markers that have a clinical impact in terms of cardiovascular risk reduction.

Maternal blood glucose regulation adaptation to pregnancy aims to support fetal growth but may also lead to the development of gestational diabetes mellitus, the most common pregnancy complication. MiRNAs are small RNA molecules secreted and stable in the blood, where they could have paracrine hormone-like functions (ribo-hormone) and regulate metabolic processes including fetal growth and glucose metabolism. The objective of this study was to identify plasmatic microRNA (miRNAs) measured during the first trimester of pregnancy that were associated with glucose levels during a 75 g oral glucose tolerance test (OGTT) at ~26 weeks of pregnancy. miRNAs were quantified using next-generation sequencing in 444 pregnant women and replicated in an independent cohort of 106 pregnant women. MiRNAs associated with glucose levels were identified with the DESeq2 package. We identified 24 miRNAs associated with fasting glycemia, of which 18 were common to both cohorts (q-value < 0.1). However, no association was found between miRNAs and 1 h or 2 h post OGTT glycemia. To conclude, we identified 18 miRNAs early in pregnancy that were associated with fasting blood glucose measured 3 months later. Our findings offer new insights into the mechanisms involved in fasting glucose homeostasis regulation in pregnancy, which is critical to understanding how gestational diabetes develops.

UNASSIGNED: Fenugreek plant (Trigonella foenum-graecum) constitutes a traditionally acclaimed herbal remedy for many human ailments including diabetes, obesity, neurodegenerative diseases, and reproductive disorders. It is also used as an effective anti-oxidative, anti-inflammatory, antibacterial, and anti-fungal agent. The seed of the plant is especially enriched in several bioactive molecules including polyphenols, saponins, alkaloids, and flavonoids and has demonstrated potential to act as an antidiabetic phytotherapeutic. A novel patented formulation (Fenfuro®) was developed in our laboratory from the fenugreek seeds which contained >45% furostanolic saponins (HPLC).
UNASSIGNED: A placebo-controlled clinical compliance study was designed to assess the effects of complementing Fenfuro® on a randomized group of human volunteers on antidiabetic therapy (Metformin and sulphonylurea) in controlling the glycemic index along with simultaneous safety assessment.
UNASSIGNED: In a randomized double-blind, placebo-controlled trial, 42 individuals (21 male and 21 female volunteers) in the treatment group (out of 57 enrolled) and 39 individuals (17 male and 22 female volunteers) in the placebo group (out of 47 enrolled), all on antidiabetic therapy with Metformin/Metformin with sulphonyl urea within the age group of 18-65 years were administered either 1,000 mg (500 mg × 2) (Fenfuro®) capsules or placebo over a period of 12 consecutive weeks. Fasting and postprandial glucose along with glycated hemoglobin were determined as primary outcomes to assess the antidiabetic potential of the formulation. Moreover, in order to evaluate the safety of the formulation, C-peptide and Thyroid Stimulating Hormone (TSH) levels as well as immunohematological parameters were assessed between the treatment and placebo groups at the completion of the study.
UNASSIGNED: After 12 weeks of administration, both fasting as well as postprandial serum glucose levels decreased by 38 and 44% respectively in the treatment group. Simultaneously, a significant reduction in glycated hemoglobin by about 34.7% was also noted. The formulation did not have any adverse effect on the study subjects as there was no significant change in C- peptide level and TSH level; liver, kidney, and cardiovascular function was also found to be normal as assessed by serum levels of key immunohematological parameters. No adverse events were reported.
UNASSIGNED: This clinical compliance study re-instated and established the safety and efficacy of Fenfuro® as an effective phytotherapeutic to treat hyperglycemia.

UNASSIGNED: Identifying simple markers of risk for worsening glucose can allow care providers to target therapeutic interventions according to risk of worsening glycemic control. We aimed to determine which routine clinical measures herald near-term glycemic worsening in early type 2 diabetes(T2D).
UNASSIGNED: The Early Diabetes Intervention Program (EDIP) was a clinical trial in individuals with screendetected T2D [HbA1C 6.3+0.63%(45+5mmol/mol)]. During the trial some participants experienced worsening fasting blood glucose (FBG). We investigated the time course of FBG, HbA1c, weight, and other clinical factors to determine which might herald glycemic worsening over the next year.
UNASSIGNED: Progressors (62/219, 28.5%) had higher FBG than non-progressors at baseline [118 vs 130mg/dL (6.6 vs 7.2 mmol/L), p=<0.001]. FBG was stable except in the year of progression, when progressors exhibited a large 1-year rise [mean change 14.2mg/dL(0.79 mmol/L)]. Current FBG and antecedent year change in FBG were associated with progression(p<0.01), although the magnitude of change was too small to be of clinical utility (0.19 mg/dL; 0.01 mmol/L). Current or antecedent year change in HbA1c, weight, TG or HDL were not associated with progression. In the year of glycemic worsening, rising glucose was strongly associated with a concurrent increase in weight (p<0.001).
UNASSIGNED: Elevated FBG but not HbA1c identified individuals at risk for imminent glycemic worsening; the subsequent large rise in glucose was associated with a short-term increase in weight. Glucose and weight surveillance provide actionable information for those caring for patients with early diabetes.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.