Beta cell function, incretin hormones, and incretin effect in obese children and adolescents with prediabetes.

BACKGROUND: Defects of incretin hormones and incretin effect may be underlying mechanisms of abnormal glucose metabolism in youth. OBJECTIVE: To assess incretin hormone dynamics during an oral glucose tolerance test (OGTT) and incretin effect in obese children with prediabetes in comparison with those with normal glucose tolerance (NGT). METHODS: Overweight and obese children were enrolled and classified according to OGTT results as NGT and prediabetes. Insulin sensitivity, insulin secretion, incretin hormone concentrations during OGTT; and incretin effect derived from OGTT and intravenous glucose tolerance test were determined and compared between NGT and prediabetes groups. RESULTS: Sixty-three patients (43 NGT and 20 prediabetes) were enrolled. Their median (interquartile range) age was 12.5 (11.1, 13.8) years. Peak glucagon-like peptide-1 (GLP-1) was demonstrated at 30 min during OGTT and was higher in the prediabetes group (49.2 [35.6, 63.6] versus 36.5 [27.6, 44.2] pmol/L, p = 0.009). However, incremental areas under the curves (iAUCs) of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were not different between the two groups. There was no difference in incretin effect between NGT and prediabetes (NGT: 66.5% [60.2%, 77.5%] vs. prediabetes: 70.0% [61.5%, 75.0%], p = 0.645). Incretin effect had positive correlations with iAUCs of both GLP-1 and GIP (GLP-1: r = 0.40, p = 0.004 and GIP: r = 0.37, p = 0.009). CONCLUSIONS: Comparing between obese children with prediabetes and NGT, there were no differences in overall incretin hormone changes during OGTT and incretin effect. Incretin effect was positively correlated with iAUCs of GLP-1 and GIP.

The Relationship Between Continuous Glucose Monitoring and OGTT in Youth and Young Adults With Cystic Fibrosis.

CONTEXT: Early glucose abnormalities in people with cystic fibrosis (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized. OBJECTIVE: This work aimed to determine the relationship between CGM and common OGTT-derived estimates of ß-cell function, including C-peptide index and oral disposition index (oDI) and to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis-related diabetes (CFRD). METHODS: PwCF not on insulin and healthy controls aged 6 to 25 years were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson correlation coefficient was used to test the association between select CGM and fsOGTT measures. Receiver operating curve (ROC) analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD. RESULTS: A total of 120 participants (controls = 35, CF = 85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r = -0.45, P < .001) and oDIcpeptide (C-peptide index)(1/cpep0) (r = -0.48, P < .0001). In PwCF, CGM variables had ROC - areas under the curve ranging from 0.43 to 0.57 for prediabetes and 0.47 to 0.6 for CFRD. CONCLUSION: Greater glycemic variability on CGM correlated with reduced ß-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically relevant nonglycemic outcomes in PwCF.

Association of leukocyte counts in the first trimester with glucose intolerance during pregnancy.

AIMS/INTRODUCTION: We investigated the association between leukocyte counts and glucose challenge test (GCT) level during pregnancy. MATERIALS AND METHODS: We collected prenatal information of women who had their first clinic visit in early pregnancy. Women underwent GCT at 24-28 gestational weeks, and a result of ≥7.8 mmol/L was considered positive. Participants were divided into quartiles of leukocyte counts, and association with GCT results and positive rate were analyzed by logistic regression. RESULTS: Among 20,707 pregnant women, the median of leukocyte counts was higher in the positive group than the normal group (8.5 × 109 /L vs 8.2 × 109 /L, P < 0.01). There was a linear trend in GCT results and positive rate with increasing leukocyte quartiles. Compared with the lowest quartile, the highest leukocyte quartile (>9.70 × 109 /L) was significantly associated with positive GCT results (adjusted odds ratio 1.378, 95% confidence interval 1.246-1.524), and the linear relationship between increased risk of positive result and increasing leukocyte quartiles persisted (P for linear trend <0.01). In multivariable analysis, the risk of a positive result increased by 2.2% with each 1-unit increase in leukocyte counts (adjusted odds ratio 1.022, 95% confidence interval 1.011-1.033). CONCLUSIONS: Elevated leukocyte counts in early pregnancy were independently and linearly associated with the risk of positive GCT levels, indicating that inflammation might play an important role in the development of gestational diabetes mellitus.

Distribution of normal and pathological OGTTs among pregnant population and non-pregnant women with PCOS - the cross-sectional study.

ABSTRACT: Both pregnancy, as physiological, and polycystic ovary syndrome (PCOS), as a pathological condition, carry the risk for developing glucose metabolism abnormalities. In this retrospective cross-sectional study, we hypothesized that pregnancy as a physiological condition carries a higher likelihood for abnormal oral glucose tolerance test (OGTT) results than PCOS as a pathological condition.We have compared the prevalence and likelihood ratios for abnormal OGTT results between non-pregnant women with PCOS (Group A) and pregnant women at 24 to 28 weeks of gestation (Group B). Participants of both study groups underwent glucose tolerance testing with 75 g glucose OGTT. During the study period, 7411 women were tested, 3932 women encompassed Group A, and 3479 women comprised Group B.The numbers of yearly tested pregnant women and the corresponding proportion of tested women among all study participants have decreased during the study period, from 766 to 131 and 89.1% to 20.5%, respectively. Group A had a significantly lower prevalence (4.4%) of pathological OGTT results compared to Group B (8.1%). This has resulted in a 45.427 likelihood ratio (P < .001) for abnormal OGTT results in pregnant women compared to non-pregnant women with PCOS.We might conclude that pregnancy could have a more challenging influence on glucose metabolism and that carries higher risks for abnormal glucose metabolism than PCOS. The awareness of obstetricians regarding physiological changes during pregnancy that predisposes abnormal glucose metabolism is decreasing over time and the compliance concerning OGTT testing of pregnant women is decreasing too.

DEVELOPING twin-specific 75-g oral glucose tolerance test diagnostic thresholds for gestational diabetes based on the risk of future maternal diabetes: a population-based cohort study.

OBJECTIVE: To develop twin-specific outcome-based oral glucose tolerance test (OGTT) diagnostic thresholds for GDM based on the risk of future maternal type-2 diabetes. DESIGN: A population-based retrospective cohort study (2007-2017). SETTING: Ontario, Canada. METHODS: Nulliparous women with a live singleton (n = 55 361) or twin (n = 1308) birth who underwent testing for gestational diabetes mellitus (GDM) using a 75-g OGTT in Ontario, Canada (2007-2017). We identified the 75-g OGTT thresholds in twin pregnancies that were associated with similar incidence rates of future type-2 diabetes to those associated with the standard OGTT thresholds in singleton pregnancies. RESULTS: For any given 75-g OGTT value, the incidence rate of future maternal type-2 diabetes was lower for women with a twin than women with a singleton pregnancy. Using women with a negative OGTT as reference, the risk of future maternal type-2 diabetes in twin pregnancies with a positive OGTT based on the standard OGTT thresholds (9.86 per 1000 person years, adjusted hazard ratio (aHR) 4.79, 95% CI 2.69-8.51) was lower than for singleton pregnancies with a positive OGTT (18.74 per 1000 person years, aHR 8.22, 95% CI 7.38-9.16). The twin-specific OGTT fasting, 1-hour and 2-hour thresholds identified in the current study based on correlation with future maternal type-2 diabetes were 5.8 mmol/l (104 mg/dl), 11.8 mmol/l (213 mg/dl) and 10.4 mmol/l (187 mg/dl), respectively. CONCLUSIONS: We identified potential twin-specific OGTT thresholds for GDM that are associated with a similar risk of future type-2 diabetes to that observed in women diagnosed with GDM in singleton pregnancies based on standard OGTT thresholds. TWEETABLE ABSTRACT: Potential twin-specific OGTT thresholds for GDM were identified.

A prospective cohort study of postpartum glucose metabolic disorders in early versus standard diagnosed gestational diabetes mellitus.

Early gestational diabetes mellitus (eGDM) is diagnosed when fasting plasma glucose before 24 weeks of gestation (WG) is ≥ 5.1 mmol/L, whilst standard GDM is diagnosed between 24 and 28 WG by oral glucose tolerance test (OGTT). eGDM seems to have worse obstetric outcomes than standard GDM. We compared the rates of postpartum glucose metabolism disorders between women with early versus standard GDM in this prospective study on women with GDM from three university hospitals between 2014 and 2016. Patients were included if they were < 24 WG with at least one risk factor for GDM and excluded if they had type 2 diabetes. Patients were assigned to Group 1 (G1) for eGDM according to IADPSG: fasting blood glucose < 24 WG between 5.1 and 7 mmol/L. Group 2 (G2) consisted of patients presenting a standard GDM at 24-28 WG on OGTT results according to IADPSG: T0 ≥ 5.1 mmol/L or T60 ≥ 10.0 mmol g/L or T120 ≥ 8.5 mmol/L. The primary outcome was postpartum OGTT result. Five hundred patients were analysed, with 273 patients undergoing OGTT at 4-18 weeks postpartum: 192 patients in G1 (early) and 81 in G2 (standard). Patients in G1 experienced more insulin therapy during pregnancy than G2 (52.2% versus 32.5%, p < 0.001), but no patients were taking insulin postpartum in either group. G1 patients experienced less preterm labour (2.6% versus 9.1%, p = 0.043), more induced deliveries (38% versus 25%, p = 0.049) and reduced foetal complications (29.2% versus 42.0%, p = 0.048). There was no significant difference in the rate of postpartum glucose metabolism disorders (type 2 diabetes, impaired glucose tolerance, impaired fasting glycaemia) between groups: 48/192 (25%) in G1 and 17/81 (21%) in G2, p = 0.58. Thus the frequency of early postpartum glucose metabolism disorders is high, without difference between eGDM and standard GDM. This supports measurement of fasting plasma glucose before 24 WG and the threshold of 5.1 mmol/L seems appropriate until verification in future studies.Trial registration: NCT01839448, ClinicalTrials.gov on 22/04/2013.

Changes in Plasma Metabolome Profiles Following Oral Glucose Challenge among Adult Chinese.

Little is known about changes in plasma metabolome profiles during the oral glucose tolerance test (OGTT) in Chinese. We aimed to characterize plasma metabolomic profiles at 0 and 2 h of OGTT and their changes in individuals of different glycemic statuses. A total of 544 metabolites were detected at 0 and 2 h of OGTT by a nontarget strategy in subjects with normal glucose (n = 234), prediabetes (n = 281), and newly diagnosed type 2 diabetes (T2D) (n = 66). Regression model, mixed model, and partial least squares discrimination analysis were applied. Compared with subjects of normal glucose, T2D cases had significantly higher levels of glycerone at 0 h and 22 metabolites at 2 h of OGTT (false discovery rate (FDR) < 0.05, variable importance in projection (VIP) > 1). Seven of the twenty-two metabolites were also significantly higher in T2D than in prediabetes subjects at 2 h of OGTT (FDR < 0.05, VIP > 1). Two hours after glucose challenge, concentrations of 35 metabolites (normal: 18; prediabetes: 23; T2D: 13) significantly increased (FDR < 0.05, VIP > 1, fold change (FC) > 1.2), whereas those of 45 metabolites (normal: 36; prediabetes: 29; T2D: 18) significantly decreased (FDR < 0.05, VIP > 1, FC < 0.8). Distinct responses between cases and noncases were detected in metabolites including 4-imidazolone-5-acetate and 4-methylene-L-glutamine. More varieties of distinct metabolites across glycemic statuses were observed at 2 h of OGTT compared with fasting state. Whether the different patterns and responsiveness of certain metabolites in T2D reflect a poor resilience of specific metabolic pathways in regaining glucose homeostasis merits further study.

Abnormal glucose challenge test in absence of oral glucose tolerance test - are there consequences?

This is a retrospective analysis of mothers with abnormal 1-hour, 50-grams glucose challenge test (GCT) who did not take a 3-hour, 100-gram oral glucose tolerance test (OGTT). This study group of women was compared to three control groups, based on an OGTT diagnostic test- normal OGTT, single pathological value and gestational diabetes mellitus. Overall- 4,185 women were included and sub-divided accordingly into four groups: Group A-340 (8.12%)- no OGTT; Group B-2,585 (61.77%)- Norm OGTT (All values normal); Group C- 564 (13.48%)- SinOGTT (single pathological value) and Group D- 696 (16.63%)- Gestational Diabetes Mellitus (GDM, ≥ 2 pathological values). Groups A, C and D had higher rates of intrapartum Caesarean Delivery (10.29%, 11.52% and 10.19% vs. 8.43%, p < .0001). Group A had highest rates of neonatal adverse outcomes, as neonatal intensive care unit (NICU) admission (12.4% vs. 8.4%, 11.0% and 10.0%, p = .039), small for gestational age (SGA) neonates (7.0% vs. 5.3%, 3.7% and 6.0%, p = .0092) and neonatal hypoglycaemia (3.5% vs. 1.3%, 3.2% and 2.9%, p = .007). A multivariable regression revealed that having an abnormal GCT without an OGTT was an independent risk factor for neonatal intensive care unit admission, neonatal hypoglycaemia and intrapartum caesarean delivery. We concluded that women with pathological GCT who did not complete OGTT have higher rates of obstetric adverse outcomes. They should be closely monitored during delivery and should not be overlooked.IMPACT STATEMENTWhat is already known on this subject? Adverse outcomes of gestational diabetes mellitus are well established. But, the group of women who fail to complete a confirmatory OGTT following a pathological GCT is not well described.What the results of this study add? Our results point out that women who fail to complete an OGTT, suffer from higher rates of obstetric complications, presumably attributed to disrupted glucose values, but also to poor prenatal care.What the implications are of these findings for clinical practice and/or further research? These women should not be overlooked. They should be closely monitored during labour and delivery.

Patterns of changes in fasting plasma glucose, hemoglobin A1c and the area under the curve during oral glucose tolerance tests in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

AIM: This study aimed to identify the patterns of changes in glycemic indices over time in prediabetics and to classify these subjects as either having a high or low risk for developing diabetes in future. METHODS: This prospective 16-year cohort study was conducted among 1228 prediabetic subjects. Three measurements including first visit, mean values during the follow-up period, and last visit from fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), and area under the curve during an oral glucose tolerance test (OGTT AUC) were used to evaluate the patterns of changes by using the latent Markov model (LMM). RESULTS: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The LMM identified 2 latent states of subjects in terms of changes in FPG, HbA1c, OGTT AUC, and the combination of these glycemic measures: a low tendency to progress diabetes and a high tendency to progress diabetes with the latent state sizes (87, 13%), (94, 6%), (57, 43%), and (84, 16%), respectively. The LMM showed that the probability of transitioning from a low tendency to a high tendency to progress diabetes was higher than the probability of transitioning in the opposite direction. CONCLUSION: Based on a long-term evaluation of patterns of changes in glycemic indices, we classified prediabetic subjects into 2 groups (high or low risk to progress diabetes states in future). Also, the method used enabled us to estimate the transition probabilities from low- to high-risk states and vice versa. Our results reemphasized the values of all 3 glycemic measures in clinical settings for identifying prediabetic people with a high risk of progressing diabetes and the need for more effective prevention strategies, which should be conducted as urgently in prediabetic life as high-risk subjects.

The evaluation of intracellular energy metabolism in prediabetic patients and patients newly diagnosed with type 2 diabetes mellitus

Background/aim: Increased susceptibility to infections is a serious problem in diabetics. Impairment in the energy metabolism of the immune system is the main source of the problem. Early diagnosis of the impairment in energy metabolism is crucial. Our study aimed to investigate the energy metabolism in leukocytes in patient groups such as prediabetics and patients newly diagnosed with type 2 diabetes mellitus. Materials and methods: Our study included 21 newly diagnosed type 2 diabetic patients (NDDP), 30 prediabetic patients, and 22 adult volunteers. 75 g oral glucose tolerance test (OGTT) was applied to all patients included in the study. Blood samples were taken after 9-16 h of fasting and fasting blood glucose (FBG), postprandial blood glucose (PBG) levels, total cholesterol (TC), triglyceride (TG), high- density lipoprotein (HDL), fasting serum insulin, and hemoglobin A1c (HbA1c) levels were evaluated. After the cells were completely lysed, citrate levels from the released mononuclear leukocyte cells (MNC) content were manually studied, and lactate levels were applied to the autoanalyzer with the lactate kit. Lactate and citrate results were calculated as µg/mL. Statistical comparisons were done using Chi-square test, Mann-Whitney U test and student's t test, and P < 0.05 values were accepted as significant. Results: A significant difference was found between the controls and the other groups (newly diagnosed diabetic patients (NDDP), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT)) in terms of FBG levels (P < 0.001, P < 0.001 and P < 0.001, respectively). IFG and IGT patients had significantly higher PBG levels compared to the control group (P = 0.009 and P < 0.001, respectively). There was a significant difference between the IFG and IGT patients in terms of insulin levels (P = 0.019). There was a significant relationship between FBG levels and lactate production only in the NDDP group (r = 0.610, P = 0.003) Conclusion: The metabolic effects of hyperglycemia on leukocytes is in direction of anaerobic glycolysis. The increased anaerobic pathway is closely related to blood glucose levels and insulin resistance.

Comparison of oral glucose tolerance test and ambulatory glycaemic profiles in pregnant women in Uganda with gestational diabetes using the FreeStyle Libre flash glucose monitoring system.

BACKGROUND: The diagnosis of hyperglycaemia in sub-Saharan Africa (SSA) is challenging. Blood glucose levels obtained during oral glucose tolerance test (OGTT) may not reflect home glycaemic profiles. We compare OGTT results with home glycaemic profiles obtained using the FreeStyle Libre continuous glucose monitoring device (FSL-CGM). METHODS: Twenty-eight women (20 with gestational diabetes [GDM], 8 controls) were recruited following OGTT between 24 and 28 weeks of gestation. All women wore the FSL-CGM device for 48-96 h at home in early third trimester, and recorded a meal diary. OGTT was repeated on the final day of FSL-CGM recording. OGTT results were compared with ambulatory glycaemic variables, and repeat OGTT was undertaken whilst wearing FSL-CGM to determine accuracy of the device. RESULTS: FSL-CGM results were available for 27/28 women with mean data capture 92.8%. There were significant differences in the ambulatory fasting, post-prandial peaks, and mean glucose between controls in whom both primary and secondary OGTT was normal (n = 6) and those with two abnormal OGTTs or "true" GDM (n = 7). There was no difference in ambulatory mean glucose between these controls and the 13 women who had an abnormal primary OGTT and normal repeat OGTT. These participants had significantly lower body mass index (BMI) than the true GDM group (29.0 Vs 36.3 kg/m2, p-value 0.014). Paired OGTT/FSL-CGM readings revealed a Mean Absolute difference (MAD) -0.58 mmol/L and Mean Absolute Relative Difference (MARD) -11.9%. Bland-Altman plot suggests FSL-CGM underestimated blood glucose by approximately 0.78 mmol/L. CONCLUSION: Diagnosis of GDM on a single OGTT identifies a proportion of women who do not have a significantly higher home glucose levels than controls. This raises questions about factors which may affect the reproducibility of OGTT in this population, including food insecurity and atypical phenotypes of diabetes. More investigation is needed to understand the suitability of the OGTT as a diagnostic test in sub-Saharan Africa.

A simplified diagnostic work-up for the detection of gestational diabetes mellitus in low resources settings: achievements and challenges.

PURPOSE: Modern strategies for the screening and diagnosis of Gestational Diabetes Mellitus (GDM) rely on universal Oral Glucose Tolerance Test (OGTT). However, they are unsustainable in low-income countries. In this study, we aimed at assessing the feasibility of a simplified diagnostic policy. METHODS: The study took place in an urban referral hospital in Freetown, Sierra Leone. During an 11-month period, pregnant women were offered capillary blood test for glucose assessment. They could be screened at any time during pregnancy. GDM was diagnosed if fasting glucose was ≥ 92 mg/dl or if the OGTT was positive. The latter was prescribed only to women presenting after 24 weeks' gestation with at least one risk factor for GDM and fasting capillary glucose between 85 and 91 mg/dl. A definitive diagnosis required confirmation to this aim, women with values above the thresholds were invited to refer the next working day for repeating the test after fasting overnight. RESULTS: Overall, 7827 women were referred for screening, of whom 6872 (87%) underwent at least one capillary glucose assessment. However, 895 of those who had a positive test did not return for confirmation. Overall, a definite assessment could be done in 5799 subjects corresponding to 76% (95% CI 75-77%) of those eligible. GDM was diagnosed in 128 women (1.9%, 95% CI 1.6-2.2%). Based on an expected confirmation rate of 22% (calculated from those who referred for confirmation) in the 895 women who did not come back, one could infer that GDM would have been diagnosed in additional 197 women, raising the prevalence to 4.7% (95% CI 4.2-5.3%). CONCLUSION: Three quarters of subjects could be assessed with our approach. Data also suggest that GDM is not rare even if identification of affected cases remains challenging.

Size and Shape of Associations of OGTT as Well as Mediating Effects on Adverse Pregnancy Outcomes Among Women With Gestational Diabetes Mellitus: Population-Based Study From Southern Han Chinese.

Objective: To explore the size and shape association of OGTT values with adverse pregnancy complications among women with gestational diabetes mellitus (GDM) in Southern Han Chinese population and further analyze their mediating effects with maternal age in outcomes. Methods: 6,861 women with GDM were included in the study. Logistic regression was used to identify the correlations between OGTT values and adverse pregnancy outcomes of GDM. Restricted cubic spline nested logistic regression was conducted to investigate potential non-linear and linear associations. Mediating effect among maternal age, OGTT and adverse outcomes were explored. Results: Women with GDM had a mean age of 31.83, and 24.49% had advanced maternal age (≥35 years). In logistic regression with adjustment, compared with lower OGTT0 (<5.1 mmol/L), GDM patients with higher OGTT0 (≥5.1 mmol/L) exhibited 1.891 (95% CI: 1.441-2.298, P < 0.001), 1.284 (1.078-1.529, P = 0.005), 1.285 (1.065-1.550, P = 0.009), and 1.302 (1.067-1.590, P = 0.010) times increased risk of hypertensive disorders of pregnancy (HDP), preterm, neonatal hyperbilirubinemia, and macrosomia, respectively. GDM patients with higher OGTT1 (≥10 mmol/L) had only found to exhibited 1.473-fold (1.162-1.867, P = 0.001) increasing risk of HDP than those with lower OGTT1 (<10 mmol/L). No adverse outcome was identified to associate with higher OGTT2 (≥8.5 mmol/L). Linear relationships (non-linear P > 0.05) were observed between OGTT0 and HDP, preterm, neonatal hyperbilirubinemia, and macrosomia in both maternal age groups (<35 and ≥35 years). Non-linear associations of OGTT1 with incidence of HDP, preterm, and neonatal hyperbilirubinemia were detected in GDM patients younger than 35 years (non-linear P = 0.037, P = 0.049, P = 0.039, respectively), rising more steeply at higher values. Similar non-linearity was noted for OGTT2 with HDP in older patients. All OGTT values had significant mediating effects on some special complications caused by higher age. Conclusion: Higher fasting plasma glucose was more strongly linked to adverse pregnancy outcomes among GDM patients. Both linearity and Non-linearity of associations between glucose and complications should be taken into account. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT is needed.

Barriers to completing oral glucose tolerance testing in women at risk of gestational diabetes.

AIM: Complications of gestational diabetes (GDM) can be mitigated if the diagnosis is recognized. However, some at-risk women do not complete antenatal diagnostic oral glucose tolerance testing (OGTT). We aimed to understand reasons contributing to non-completion, particularly to identify modifiable factors. METHODS: Some 1906 women attending a tertiary UK obstetrics centre (2018-2019) were invited for OGTT based on risk-factor assessment. Demographic information, test results and reasons for non-completion were collected from the medical record. Logistic regression was used to analyse factors associated with non-completion. RESULTS: Some 242 women (12.3%) did not complete at least one OGTT, of whom 32.2% (n = 78) never completed testing. In adjusted analysis, any non-completion was associated with younger maternal age [≤ 30 years; odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6-3.4; P < 0.001], Black African ethnicity (OR 2.7, 95% CI 1.2-5.5; P = 0.011), lower socio-economic status (OR 0.9, 95% CI 0.8-1.0; P = 0.021) and higher parity (≥ 2; OR 1.8, 95% CI 1.1-2.8; P = 0.013). Non-completion was more likely if testing indications included BMI ≥ 30 kg/m2 (OR 1.7, 95% CI 1.1-2.4; P = 0.009) or family history of diabetes (OR 2.2, 95% CI 1.5-3.3; P < 0.001) and less likely if the indication was an ultrasound finding (OR 0.4, 95% CI 0.2-0.9; P = 0.035). We identified a common overlapping cluster of reasons for non-completion, including inability to tolerate test protocol (21%), social/mental health issues (22%), and difficulty keeping track of multiple antenatal appointments (15%). CONCLUSIONS: There is a need to investigate methods of testing that are easier for high-risk groups to schedule and tolerate, with fuller explanation of test indications and additional support for vulnerable groups.

Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non-obese men.

Individuals with a monophasic glucose response curve (GRC) during a 75-g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non-obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue-specific insulin sensitivity and insulin clearance using a two-step hyperinsulinemic-euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non-obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.

Heritability of Curve Patterns in Oral Glucose Tolerance Test.

Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.

Glucose Effectiveness from Short Insulin-Modified IVGTT and Its Application to the Study of Women with Previous Gestational Diabetes Mellitus.

BACKGROUND: This study aimed to design a simple surrogate marker (i.e., predictor) of the minimal model glucose effectiveness (SG), namely calculated SG (CSG), from a short insulin-modified intravenous glucose tolerance test (IM-IVGTT), and then to apply it to study women with previous gestational diabetes mellitus (pGDM). METHODS: CSG was designed using the stepwise model selection approach on a population of subjects (n=181) ranging from normal tolerance to type 2 diabetes mellitus (T2DM). CSG was then tested on a population of women with pGDM (n=57). Each subject underwent a 3-hour IM-IVGTT; women with pGDM were observed early postpartum and after a follow-up period of up to 7 years and classified as progressors (PROG) or non-progressors (NONPROG) to T2DM. The minimal model analysis provided a reference SG. RESULTS: CSG was described as CSG=1.06×10⁻²+5.71×10⁻²×KG/Gpeak, KG being the mean slope (absolute value) of loge glucose in 10-25- and 25-50-minute intervals, and Gpeak being the maximum of the glucose curve. Good agreement between CSG and SG in the general population and in the pGDM group, both at baseline and follow-up (even in PROG and NONPROG subgroups), was shown by the Bland-Altman plots (<5% observations outside limits of agreement), and by the test for equivalence (equivalence margin not higher than one standard deviation). At baseline, the PROG subgroup showed significantly lower SG and CSG values compared to the NONPROG subgroup (P<0.03). CONCLUSION: CSG is a valid SG predictor. In the pGDM group, glucose effectiveness appeared to be impaired in women progressing to T2DM.

Associations of sleep duration, sedentary behaviours and energy expenditure with maternal glycemia in pregnancy.

BACKGROUND: Women with high levels of physical activity (PA) are less likely to develop gestational diabetes mellitus (GDM), but the relations with sleep and sedentary behaviours (SB) are more controversial. We aimed to investigate all three components (sleep, PA, and SB) and their association with maternal glucose in pregnancy. METHODS: We included 766 pregnant women recruited at first trimester and that we followed at second trimester. We collected blood samples, anthropometry and standardized questionnaires about lifestyle including PA, SB, and sleep duration at both visits. Women completed a 50 g glucose challenge test at first trimester and 75-g oral glucose tolerance test (OGTT) at second trimester. We conducted regression analyses to test cross-sectional associations between sleep, PA, and SB with maternal glucose levels while taking into account potential confounders (maternal age, pre-pregnancy body mass index (BMI), gravidity, and smoking). We considered linear and quadratic relationships. RESULTS: At first trimester, we observed a linear relationship between shorter sleep duration and higher glucose levels, which was attenuated after adjustments for confounders. At second trimester, we found a quadratic relationship between sleep and glucose showing lowest levels at fasting and 1 h-post OGTT for women who slept 6-10 h/night. This association remained significant after adjusting for confounders and taking into account PA and/or SB. Greater amount of SB was associated with higher 1 h-glucose after adjustment for confounders (ß = 0.132; SE = 0.047; P = 0.005). CONCLUSIONS: Sleep duration is associated with glucose regulation in pregnancy, independently of PA and SB, and this association varies according to the period of gestation.

The implications of dysglycaemia on aerobic exercise and ventilatory function in cystic fibrosis.

BACKGROUND: The development of cystic fibrosis (CF)-related diabetes (CFRD) in paediatric groups is associated with a reduced aerobic fitness. However, this has yet to be investigated in adults with more severe lung disease. METHODS: Cardiopulmonary exercise and glycaemic control tests were retrospectively analysed in 46 adults with CF (age: 26.9 y [range: 16.3-66.5 y]; forced expiratory volume in 1s: 65.3% [range: 26.8-105.7%]; 26 males), diagnosed with CFRD (n = 19), impaired glucose tolerance (IGT; n = 8) or normal glucose tolerance (NGT; n = 19). RESULTS: Maximal oxygen uptake (V˙O2max) was reduced in adults with IGT and CFRD compared to their age- and gender-matched counterparts with NGT (p < 0.05); however, there was no difference when lung function was included as a covariate (all p > 0.05). V˙O2max was greater in adults who experienced post-reactive hypoglycaemia vs. NGT without hypoglycaemia (p < 0.05). The frequency of ventilatory limitation (84%, 63% and 37%, respectively; p < 0.05) but not ventilation-perfusion mismatch (42%, 38% and 16%, respectively; p > 0.05), was greater with CFRD and IGT vs. NGT. There was also no difference in arterial oxygen saturation changes between groups (p > 0.05). Gender and body mass index were significant predictors of V˙O2max (adjusted R2 = 0.37, p < 0.01), but glycaemic control did not explain additional variance (p > 0.05). CONCLUSIONS: Adults with CF-related dysglycaemia had a reduced V˙O2max compared to age- and gender-matched counterparts, due to a greater degree of CF lung disease in these populations.

Perinatal outcomes for untreated women with gestational diabetes by IADPSG criteria: a population-based study.

OBJECTIVE: To estimate the risk for adverse perinatal outcomes for women who met the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria but not the two-step criteria for gestational diabetes mellitus (GDM). DESIGN: Population-level cross-sectional study. SETTING: Ontario, Canada. POPULATION: A total of 90 140 women who underwent a 75-g oral glucose tolerance test. METHODS: Women were divided into those who met the diagnostic thresholds for GDM by two-step criteria and were therefore treated, those who met only the IADPSG criteria for GDM and so were not treated, and those who did not have GDM by either criteria. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy, preterm delivery, primary caesarean section, large-for-gestational-age, shoulder dystocia and neonatal intensive care unit admission. RESULTS: Women who met the IADPSG criteria had an increased risk for all adverse perinatal outcomes compared with women who did not have GDM. Women with GDM by two-step criteria also had an increased risk of most outcomes. However, their risk for large-for-gestational-age neonates and for shoulder dystocia was actually lower than that of women who met IADPSG criteria. CONCLUSION: Women who met IADPSG criteria but who were not diagnosed with GDM based on the current two-step diagnostic strategy, and were therefore not treated, had an increased risk for adverse perinatal outcomes compared with women who do not have GDM. The current strategy for diagnosing GDM may be leaving women who are at risk for adverse events without the dietary and pharmacological treatments that could improve their pregnancy outcomes. TWEETABLE ABSTRACT: Women who meet IADPSG criteria for GDM have an increased risk for adverse perinatal outcomes compared with women without GDM.