Gestational diabetes (GDM) affects 20 million women/year worldwide and is associated with childhood obesity. Infants of affected mothers have increased adiposity from birth, which leads to obesity in ...later life. However, it remains unknown whether the effect of GDM upon neonatal body composition is due to hyperglycemia alone or is mediated by other pathways.
To investigate plasma lipid profiles in obese women according to GDM diagnosis, infant birthweight percentiles, and adiposity.
Prospective cohort from UPBEAT trial (ISRCTN 89971375).
Hospital and community.
867 obese pregnant women recruited in early pregnancy, assessed at 28 weeks for GDM. Offspring anthropometry was assessed at birth.
Neonatal birth percentile and abdominal circumference.
Lipidomic profiling in the fasting plasma oral glucose tolerance test sample using direct infusion mass spectrometry. Analysis included logistic/linear regression, unadjusted and adjusted for maternal age, body mass index, parity, ethnicity, UPBEAT trial arm, and fetal sex. The limit of significance was P = 0.05 for offspring anthropometry and P = 0.002 for lipidomic data.
GDM in obese women was associated with elevated plasma concentrations of specific diglycerides DG(32:0) and triglycerides TG(48:0), (50:1), (50:2) containing fatty acids (16:0), (16:1), (18:0), and (18:1), consistent with increased de novo lipogenesis. In the whole cohort, these species were associated with birthweight percentile and neonatal abdominal circumference. Effects upon infant abdominal circumference remained significant after adjustment for maternal glycemia.
Increased de novo lipogenesis-related species in pregnant women with obesity and GDM are associated with measures of offspring adiposity and may be a target for improving lifelong health.
We piloted a randomised controlled trial (RCT) comparing pregnancy outcomes among women with booking gestational diabetes (GDM) receiving immediate or deferred treatment.
Consecutive, consenting ...women < 20 weeks gestation, with GDM risk factors attending the hospital book-in clinic, completed an oral glucose tolerance test (OGTT). Clinicians were blinded to OGTT results. Women fulfilling World Health Organisation GDM criteria were randomised to either clinic referral /ongoing treatment (Treated Group n = 11), or no treatment (No Treatment Group n = 10). Women without 'Booking GDM' ('Decoys' n = 58) and those in the No Treatment Group had a repeat OGTT at 24-28 weeks (with GDM treated if diagnosed). Midwives and mothers were asked to complete surveys and attend focus groups before and after the study respectively regarding their experiences and expectations of the study protocol.
Sufficient women completed each step of the RCT. Gestation at OGTT was late at 18 ± 2 weeks with Treated and No Treatment groups largely similar. At 24-28 weeks gestation, GDM was present in 8/9 (89%) in the No Treatment group and 11/56 (20%) Decoys. NICU admission was highest in the Treated group (36% vs 0% p = 0.043), largely due to small for gestational age, and Large for Gestational Age babies greatest in the No Treatment group (0% vs 33% p = 0.030).
An RCT deferring 'Booking GDM' treatment is feasible. Most women with untreated 'Booking GDM' in mid 2nd trimester had GDM at 24-28 weeks. Early treatment may have both benefits and harms. A full RCT is needed.
Australia New Zealand Clinical Trials Registry ACTRN12615000974505. Registered 17th May 2015; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369100&isReview=true Retrospectively Registered.
To explore the influence of the 75 g oral glucose tolerance test (OGTT) on pregnancy outcomes and to determine the risk factors for adverse outcomes among women with gestational diabetes mellitus ...(GDM).This retrospective cohort study was conducted among women who had GDM and were treated between January 1, 2015 and December 31, 2017. The diagnostic criteria for GDM were proposed by the International Diabetes and Pregnancy Research Organization (IADPSG) in 2010. Women with GDM were stratified according to the number of abnormal OGTT values or the presence/absence of adverse pregnancy outcomes. Maternal characteristics, OGTT values, pregnancy outcomes, and the relationship between the latter 2 were analyzed.In total, 3221 pregnant women with GDM were included. The incidence of adverse outcomes was affected by maternal age (28-37 years, in particular; odds ratio OR, 1.403; 95% confidence interval CI, 1.037-1.899; P = .028), days of pregnancy (OR, 0.904; 95% CI, 0.894-0.914; P < .001), gestational weight gain (OR, 1.018; 95% CI, 1.000-1.036;, P = .048), and age of menarche (OR, 0.925; 95% CI, 0.863-0.992; P = .029). Both fasting plasma glucose (FPG) and 2-h OGTT were positively correlated with adverse outcomes, of which FPG was more predictive (FPG: OR, 1.143; 95% CI, 1.007-1.297; P = .038; 2-h OGTT: OR, 1.074; 95% CI, 1.018-1.133; P = .009). Meanwhile, higher abnormal OGTT values were associated with significantly increased risks of antenatal insulin treatment, cesarean delivery, premature delivery, gestational hypertension, premature rupture of membranes, preeclampsia, macrosomia, neonatal asphyxia, and full term low weight infants.OGTT values and the number of abnormal glucose are associated with various adverse pregnancy outcomes. Stratified management is recommended for pregnant women with GDM, especially those with fasting hyperglycemia and/or 3 abnormal OGTT values.
Screening for diabetes is typically done using hemoglobin A
(HbA
) or fasting plasma glucose (FPG). The 2019 Endocrine Society guidelines recommend further testing using an oral glucose tolerance ...test (OGTT) in older adults with prediabetic HbA
or FPG. We evaluated the impact of this recommendation on diabetes prevalence, eligibility for glucose-lowering treatment, and estimated cost of implementation in a nationally representative sample.
We included 2,236 adults aged ≥65 years without known diabetes from the 2005-2016 National Health and Nutrition Examination Survey. Diabetes was defined using:
) the Endocrine Society approach (HbA
≥6.5%, FPG ≥126 mg/dL, or 2-h plasma glucose ≥200 mg/dL among those with HbA
5.7-6.4% or FPG 100-125 mg/dL); and
) a standard approach (HbA
≥6.5% or FPG ≥126 mg/dL). Treatment eligibility was defined using HbA
cut points (≥7% to ≥9%). OGTT screening costs were estimated using Medicare fee schedules.
Diabetes prevalence was 15.7% (∼5.0 million) using the Endocrine Society's approach and 7.3% (∼2.3 million) using the standard approach. Treatment eligibility ranged from 5.4% to 0.06% and 11.8% to 1.3% for diabetes cases identified through the Endocrine Society or standard approach, respectively. By definition, diabetes identified exclusively through the Endocrine Society approach had HbA1
<6.5% and would not be recommended for glucose-lowering treatment. Screening all older adults with prediabetic HbA
/FPG (∼18.3 million) with OGTT could cost between $737 million and $1.7 billion.
Adopting the 2019 Endocrine Society guidelines would substantially increase the number of older adults classified as having diabetes, require significant financial resources, but likely offer limited benefits.
To study the effect of melatonin administration on glucose metabolism in humans in the morning and evening.
Placebo-controlled, single-blind design.
Laboratory assessments.
21 healthy women (24 ± 6 ...y; body mass index: 23.0 ± 3.3 kg/m(2)).
Glucose tolerance was assessed by oral glucose tolerance tests (OGTT; 75 g glucose) on 4 occasions: in the morning (9 AM), and evening (9 PM); each occurring 15 minutes after melatonin (5 mg) and placebo administration on 4 non-consecutive days.
Melatonin administration impaired glucose tolerance. When administered in the morning, melatonin significantly increased the incremental area under the curve (AUC) and maximum concentration (Cmax) of plasma glucose following OGTT by 186% and 21%, respectively, as compared to placebo; while in the evening, melatonin significantly increased glucose AUC and Cmax by 54% and 27%, respectively. The effect of melatonin on the insulin response to the OGTT depended on the time of day (P < 0.05). In the morning, melatonin decreased glucose tolerance primarily by decreasing insulin release, while in the evening, by decreasing insulin sensitivity.
Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. When administering melatonin, the proximity to meal timing may need to be considered, particularly in those at risk for glucose intolerance.
Abstract
Background
Indeterminate glycemia (INDET) and impaired glucose tolerance (IGT) are independently associated with cystic fibrosis-related diabetes (CFRD) risk. We determined whether patients ...meeting both criteria have increased risk of diabetes in 2 separate adult cohorts.
Methods
The Montreal Cystic Fibrosis Cohort (MCFC; n = 293 baseline and 198 for prospective analysis excluding subjects identified with incident CFRD at baseline) and the Lyon cystic fibrosis cohort Determination of the Predictive Factors in the Reversibility or the Aggravation in the Disorders of the Glucose Metabolism in Cystic Fibrosis Patients (DIAMUCO); n = 144/105 are prospective observational cohorts.
Results
In the MCFC and DIAMUCO cohorts, mean age was 25.5 ± 7.7 and 25.0 ± 8.6 years; body mass index, 21.7 ± 3.0 and 20.2 ± 2.2 kg/m2; percentage of forced expiratory volume expired in 1 sec, 73.2 ± 22.1 and 62.5 ± 21.9; and follow-up, 6.9 ± 3.8 and 2.4 ± 1.2 years, respectively. In the MCFC cohort, the IGT only and combined INDET and IGT (INDET + IGT) groups had greater risk of CFRD (P = 0.0109). In the DIAMUCO cohort, there was lower diabetes-free survival in the INDET + IGT group (P = 0.0105). In both cohorts, CFRD risk ranged from 17% in normal glucose tolerance patients up to 42% to 56% in patients with INDET + IGT.
Conclusion
Patients who meet combined criteria have a higher risk of developing diabetes probably justifying closer follow-up.
Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to ...investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT).
A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio RR) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values.
Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 95% CI: 0.04-0.36. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 95% CI 1.64-13.96). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L).
For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.
The timing of increase in 1-hour PG and its utility as an earlier predictor of both prediabetes (PreDM) and type 2 diabetes (T2D) compared to 2-hour PG (2 h-PG) are unknown. To evaluate the timing of ...crossing of the 1 h-PG ≥ 155 mg/dl (8.6 mmol/L) for PreDM and 209 mg/dl (11.6 mmol/L) for T2D and respective current 2 h-PG thresholds of 140 mg/dl (7.8 mmol/L) and 200 mg/dl (11.1 mmol/L).
Secondary analysis of 201 Southwest Native Americans who were followed longitudinally for 6–10 years and had at least 3 OGTTs.
We identified a subset of 43 individuals who first developed PreDM by both 1 h-PG and 2 h-PG criteria during the study. For most (32/43,74%), 1 h-PG ≥ 155 mg/dl was observed before 2 h-PG reached 140 mg/dl (median IQR: 1.7 -0.25, 4.59 y; mean ± SEM: 5.3 ± 1.9 y). We also identified a subset of 33 individuals who first developed T2D during the study. For most (25/33, 75%), 1 h-PG reached 209 mg/dl earlier (median 1.0 -0.56, 2.02 y; mean ± SEM: 1.6 ± 0.8 y) than 2 h-PG reached 200 mg/dl, diagnostic of T2D.
1 h-PG ≥ 155 mg/dl is an earlier marker of elevated risk for PreDM and T2D than 2 h-PG ≥ 140 mg/dl.
•Standardised preanalytical conditions during the oral glucose tolerance test are required to avoid misdiagnosis of gestational diabetes.•Delayed sample transport and processing of tubes for glucose ...measurement could cause false negative diagnosis of gestational diabetes.•The preanalytical conditions of the HAPO study are difficult to achieve in practice.•Due to common preanalytical errors, healthcare providers must interpret OGTT results with care, especially when glucose results are close to diagnostic thresholds.•Standardised preanalytical conditions during the oral glucose tolerance test are required to avoid misdiagnosis of gestational diabetes.
To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.
A whole-grain (WG)–rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 ...diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG.
The aim was to investigate WG rye, alone and with lignan supplements secoisolariciresinol diglucoside (SDG), and WG wheat diets on glucose tolerance oral-glucose-tolerance test (OGTT), other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets.
Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4–8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots.
The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (−0.06 and −0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium fold-change (FC) = 2.58, P < 0.001 compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet.
WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.
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