Post-load Glucose Concentrations Research Articles

First-trimester HbA1c in relation to plasma glucose concentrations in an oral glucose tolerance test at 12 to 16 weeks’ gestation—a population-based study

BackgroundEarly-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12–16 weeks’ gestation; and (2) pharmacologically treated early- or late-onset GDM.MethodsHbA1c was measured at 8—14 weeks’ gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12—16 weeks’ gestation (OGTT1), and if normal, repeated at 24–28 weeks’ gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2.ResultsMaternal early-pregnancy HbA1c ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA1c ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66).ConclusionsIn our population-based cohort, early-pregnancy HbA1c ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12—16 weeks’ gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.

Body surface area is positively associated with ankle-brachial index.

Ankle-brachial index (ABI) measurement is a widely used diagnostic test for lower extremity artery disease. Previously, a larger body surface area (BSA) has been associated with lower blood pressure and lower 2-h post-load glucose concentrations in the oral glucose tolerance test. Our aim was to evaluate whether BSA has an impact on ABI and the prevalence of lower ABI values. ABI measurements were performed on 972 subjects aged 45 to 70 years at high cardiovascular disease (CVD) risk. Subjects with previously diagnosed kidney disease, CVD, and diabetes were excluded. Their BSA was calculated by the Mosteller formula. Study subjects were divided into five BSA levels corresponding to 12.5th, 25th, 25th, 25th, and 12.5th percentiles of the total distribution. Effect modification by BSA in ABI between sexes was derived from a four-knot restricted cubic splines regression model. After adjustments for age, sex, pulse pressure, glucose regulation, waist circumference, alcohol intake, smoking status, leisure-time physical activity and medication, BSA level had a positive linear relationship with ABI (p for linearity <0.001). When BSA was less than 2.0 m2, there was no difference between the sexes, but when BSA was higher than 2.0 m2, men had higher ABI. BSA shows a positive linear relationship with ABI in CVD risk subjects without manifested CVD. The difference in ABI between men and women is modified by BSA and is appreciable when BSA is larger than 2.0 m2.

Large maternal waist circumference in relation to height is associated with high glucose concentrations in an early-pregnancy oral glucose tolerance test: A population-based study.

To explore the role of maternal anthropometric characteristics in early-pregnancy glycemia, we analyzed the associations and interactions of maternal early-pregnancy waist circumference (WC), height and pre-pregnancy body mass index (BMI) with plasma glucose concentrations in an oral glucose tolerance test (OGTT) at 12-16 weeks' gestation. A population-based cohort of 1361 pregnant women was recruited in South Karelia, Finland, from March 2013 to December 2016. All participants had their WC, weight, height, HbA1c , and blood pressure measured at 8-14 weeks' gestation and subsequently underwent a 2-h 75-g OGTT, including assessment of fasting insulin concentrations, at 12-16 weeks' gestation. BMI (kg/m2 ) was calculated using self-reported pre-pregnancy weight. Maternal WC ≥80 cm was defined as large. Maternal height ≥166 cm was defined as tall. Data on gestational diabetes treatment was extracted from hospital records. In the total cohort, 901 (66%) of women had an early-pregnancy WC ≥80 cm, which was associated with higher early-pregnancy HbA1c, higherconcentrationsoffasting plasma glucose and serum insulin, higherpost-load plasma glucose concentrations, higherHOMA-IR indices, higher blood pressure levels, and higherfrequencies of pharmacologically treated gestational diabetes, than early-pregnancy WC <80 cm. Maternal height ≥166 cm was negatively associated with 1- and 2-h post-load plasma glucose concentrations. Waist-to-height ratio (WHtR) >0.5 was positively associated with both fasting and post-load plasma glucose concentrations at 12-16 weeks' gestation, even when adjusted for age, smoking, nulliparity, and family history of type 2 diabetes. The best cut-offs for WHtR (0.58 for 1-h plasma glucose, and 0.54 for 2-h plasma glucose) were better predictors of post-load glucose concentrations >90th percentile than the best cut-offs for BMI (28.1kg/m2 for 1-h plasma glucose, and 26.6kg/m2 for 2-h plasma glucose), with areas-under-the-curve (95% confidence interval) 0.73 (0.68-0.79) and 0.73 (0.69-0.77), respectively, for WHtR, and 0.68 (0.63-0.74) and 0.69 (0.65-0.74), respectively, for BMI. In our population-based cohort, early-pregnancy WHtR >0.5 waspositively associatedwith both fasting and post-load glucose concentrations at 12-16 weeks' gestation and performed better than BMI in the prediction of post-load glucose concentrations >90th percentile. Overall, our results underline the importance of evaluating maternal abdominal adiposity in gestational diabetes risk assessment.

Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study

BackgroundAdaptations in lipid metabolism are essential to meet the physiological demands of pregnancy and any aberration may result in adverse outcomes for both mother and offspring. However, there is a lack of population-level studies to define the longitudinal changes of maternal circulating lipids from preconception to postpartum in relation to cardiometabolic risk factors.MethodsLC-MS/MS-based quantification of 689 lipid species was performed on 1595 plasma samples collected at three time points in a preconception and longitudinal cohort, Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). We mapped maternal plasma lipidomic profiles at preconception (N = 976), 26–28 weeks’ pregnancy (N = 337) and 3 months postpartum (N = 282) to study longitudinal lipid changes and their associations with cardiometabolic risk factors including pre-pregnancy body mass index, body weight changes and glycaemic traits.ResultsAround 56% of the lipids increased and 24% decreased in concentration in pregnancy before returning to the preconception concentration at postpartum, whereas around 11% of the lipids went through significant changes in pregnancy and their concentrations did not revert to the preconception concentrations. We observed a significant association of body weight changes with lipid changes across different physiological states, and lower circulating concentrations of phospholipids and sphingomyelins in pregnant mothers with higher pre-pregnancy BMI. Fasting plasma glucose and glycated haemoglobin (HbA1c) concentrations were lower whereas the homeostatic model assessment of insulin resistance (HOMA-IR), 2-h post-load glucose and fasting insulin concentrations were higher in pregnancy as compared to both preconception and postpartum. Association studies of lipidomic profiles with these glycaemic traits revealed their respective lipid signatures at three physiological states. Assessment of glycaemic traits in relation to the circulating lipids at preconception with a large sample size (n = 936) provided an integrated view of the effects of hyperglycaemia on plasma lipidomic profiles. We observed a distinct relationship of lipidomic profiles with different measures, with the highest percentage of significant lipids associated with HOMA-IR (58.9%), followed by fasting insulin concentration (56.9%), 2-h post-load glucose concentration (41.8%), HbA1c (36.7%), impaired glucose tolerance status (31.6%) and fasting glucose concentration (30.8%).ConclusionsWe describe the longitudinal landscape of maternal circulating lipids from preconception to postpartum, and a comprehensive view of trends and magnitude of pregnancy-induced changes in lipidomic profiles. We identified lipid signatures linked with cardiometabolic risk traits with potential implications both in pregnancy and postpartum life. Our findings provide insights into the metabolic adaptations and potential biomarkers of modifiable risk factors in childbearing women that may help in better assessment of cardiometabolic health, and early intervention at the preconception period.Trial registrationClinicalTrials.gov, NCT03531658.

Assessment of glucose levels in pregnant women with history of COVID-19 in a case-control study.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection may negatively affect glucose metabolism. This study aims to assess glucose levels, prevalence of gestational diabetes mellitus (GDM) and perinatal outcome in women with history of COVID-19. To this purpose, a group of 65 patients with history of COVID-19 and 94 control patients were retrospectively recruited among pregnant women who attended the pregnancy outpatient department between 01/2020 and 02/2022. Glucose data from an oral glucose tolerance test (OGTT), GDM status and obstetric complications were assessed. We observed no differences in average (p = 0.37), fasting (p = 0.62) or post-load glucose concentrations (60 min: p = 0.19; 120 min: p = 0.95) during OGTT. A total of 15 (23.1%) women in the COVID-19 group and 18 (19.1%) women in the control group developed GDM (p = 0.55). Moreover, caesarean section rate, weight percentiles and pregnancy outcomes were comparable between the groups (p = 0.49). In conclusion, in this study we did not identify a possible impact of COVID-19 on glucose metabolism in pregnancy, especially with regard to glucose concentrations during the OGTT and prevalence of GDM.

Dietary Acid Load Is Positively Associated With Risk of Gestational Diabetes Mellitus in a Prospective Cohort of Chinese Pregnant Women.

BackgroundGrowing evidence suggests that dietary acid load plays an important role in the development of type 2 diabetes. However, prospective studies on the relationship between dietary acid load and gestational diabetes mellitus (GDM) are limited in the pregnant population. This study aimed to investigate the effect of dietary acid load during early pregnancy on the risk of GDM in Chinese pregnant women.MethodsA total of 1,327 pregnant women were enrolled from an ongoing prospective study of the Tongji Birth cohort (TJBC) in Wuhan, China. Dietary intake was assessed before 20 weeks using a 74-item semiquantitative food frequency questionnaire (FFQ). The dietary acid load was estimated using potential renal acid load (PRAL), net endogenous acid production (NEAP), and animal protein to potassium ratio (A:P ratio). A 75g 2-h oral glucose tolerance test (OGTT) was performed at 24-28 gestational weeks to diagnose GDM.ResultsThe mean (standard deviation) values for PRAL score, NEAP score, and A:P ratio were 0.8 ± 11.3 mEq/day, 45.3 ± 16.5 mEq/day, and 9.8 ± 6.0, respectively. There was a significant positive correlation of dietary acid load with the intake of red meat, poultry, fish, and eggs, and a negative correlation with the intake of vegetables, fruits, nuts, and legumes (all P < 0.05). Compared to the lowest tertile, the highest tertile of dietary acid load, including PRAL score (odds ratio [OR]: 2.26, 95% confidence interval [CI] = 1.38–3.71, P-trend = 0.002), NEAP score (OR: 2.02, 95% CI = 1.25–3.27, P-trend = 0.009), and A:P ratio (2.08, 95% CI = 1.30–3.31, P-trend = 0.005), significantly increased the risk of GDM. In addition, the dietary acid load was also significantly associated with an increase in 1-h and 2-h post-load blood glucose concentrations (all P-trend < 0.05).ConclusionWe found a significant positive association between dietary acid load during early pregnancy and the risk of GDM in a Chinese population, suggesting that the reduction of food sources of dietary acid load may be an effective strategy for preventing the risk of GDM.

Augmented duodenal levels of sodium/glucose co-transporter 1 are associated with higher risk of nonalcoholic fatty liver disease and noninvasive index of liver fibrosis

AimsSubjects with elevated 1 h post-load glucose concentrations (1hPG) exhibit increased risk of non-alcoholic fatty liver disease (NAFLD) and duodenal sodium/glucose co-transporter 1 (SGLT-1) levels. Herein, we evaluate whether higher SGLT-1 duodenal levels are associated with NAFLD and increased risk of advance liver fibrosis. MethodsSGLT-1 levels were assessed on duodenal mucosa in 52 individuals subdivided into two groups according to ultrasonography-defined presence of NAFLD. Intracellular triglycerides levels and activation of endoplasmic reticulum (ER) stress were evaluated in human hepatocytes exposed to high-glucose concentration (HG). ResultsIndividuals with NAFLD exhibited higher duodenal SGLT-1 abundance along with raised 1hPG, as compared to those without NAFLD. The mediation analysis showed that augmented duodenal SGLT-1 levels were a predictor of NAFLD, and the link between increased duodenal SGLT-1 content and NAFLD risk was mediated by augmented 1hPG. Amongst participants with NAFLD, those with intermediate/high probability of advance liver fibrosis, estimated by NAFLD fibrosis score, exhibited higher duodenal SGLT-1 abundance and 1hPG levels as compared to the low probability group. Hepatocytes exposed to HG showed increased triglycerides accumulation and an up-regulation of ER stress pathway. ConclusionsIncreased duodenal SGLT-1 abundance and the related early post-prandial hyperglycemia are associated with NAFLD and advance liver fibrosis.

Late-Pregnancy Fetal Hypoxia Is Associated With Altered Glucose Metabolism and Adiposity in Young Adult Offspring of Women With Type 1 Diabetes.

ObjectiveTo investigate associations between exposure to fetal hypoxia and indicators of metabolic health in young adult offspring of women with type 1 diabetes (OT1D).Methods156 OT1D born between 7/1995 and 12/2000 at Helsinki University Hospital, Finland, were invited for follow-up between 3/2019 and 11/2019. A control group of 442 adults born from non-diabetic pregnancies, matched for date and place of birth, was obtained from the Finnish Medical Birth Register. In total, 58 OT1D and 86 controls agreed to participate. All OT1D had amniotic fluid (AF) sampled for erythropoietin (EPO) measurement within two days before delivery in order to diagnose fetal hypoxia. In total, 29 OTID had an AF EPO concentration <14.0 mU/l, defined as normal, and were categorized into the low EPO (L-EPO) group. The remaining 29 OT1D had AF EPO ≥14.0 mU/ml, defined as fetal hypoxia, and were categorized into the high EPO (H-EPO) group. At the age of 18-23 years, participants underwent a 2-h 75g oral glucose tolerance test (OGTT) in addition to height, weight, waist circumference, body composition, blood pressure, HbA1c, cholesterol, triglyceride, high-sensitivity CRP and leisure-time physical activity measurements.ResultsTwo OT1D were diagnosed with diabetes and excluded from further analyses. At young adult age, OT1D in the H-EPO group had a higher BMI than those in the L-EPO group. In addition, among female participants, waist circumference and body fat percentage were highest in the H-EPO group. In the OGTTs, the mean (SD) 2-h post-load plasma glucose (mmol/L) was higher in the H-EPO [6.50 (2.11)] than in the L-EPO [5.21 (1.10)] or control [5.67 (1.48)] offspring (p=0.009). AF EPO concentrations correlated positively with 2-h post-load plasma glucose [r=0.35 (95% CI: 0.07 to 0.62)] and serum insulin [r=0.44 (95% CI: 0.14 to 0.69)] concentrations, even after adjusting for maternal BMI, birth weight z-score, gestational age at birth and adult BMI. Control, L-EPO and H-EPO groups did not differ with regards to other assessed parameters.ConclusionsHigh AF EPO concentrations in late pregnancy, indicating fetal hypoxia, are associated with increased adiposity and elevated post-load glucose and insulin concentrations in young adult OT1D.

Characteristics of gestational diabetes subtypes classified by oral glucose tolerance test values.

BackgroundIn clinical practice, gestational diabetes mellitus (GDM) is treated as a homogenous disease but emerging evidence suggests that the diagnosis of GDM possibly comprises different metabolic entities. In this study, we aimed to assess early pregnancy characteristics of gestational diabetes mellitus entities classified according to the presence of fasting and/or post‐load hyperglycaemia in the diagnostic oral glucose tolerance test performed at mid‐gestation.MethodsIn this prospective cohort study, 1087 pregnant women received a broad risk evaluation and laboratory examination at early gestation and were later classified as normal glucose tolerant (NGT), as having isolated fasting hyperglycaemia (GDM‐IFH), isolated post‐load hyperglycaemia (GDM‐IPH) or combined hyperglycaemia (GDM‐CH) according to oral glucose tolerance test results. Participants were followed up until delivery to assess data on pharmacotherapy and pregnancy outcomes.ResultsWomen affected by elevated fasting and post‐load glucose concentrations (GDM‐CH) showed adverse metabolic profiles already at beginning of pregnancy including a higher degree of insulin resistance as compared to women with normal glucose tolerance and those with isolated defects (especially GDM‐IPH). The GDM‐IPH subgroup had lower body mass index at early gestation and required glucose‐lowering medications less often (28.9%) as compared to GDM‐IFH (47.8%, P = .019) and GDM‐CH (54.5%, P = .005). No differences were observed in pregnancy outcome data.ConclusionsWomen with fasting hyperglycaemia, especially those with combined hyperglycaemia, showed an unfavourable metabolic phenotype already at early gestation. Therefore, categorization based on abnormal oral glucose tolerance test values provides a practicable basis for clinical risk stratification.

Early pregnancy essential and non-essential metal mixtures and gestational glucose concentrations in the 2nd trimester: Results from project viva

Metals are involved in glucose metabolism, and some may alter glycemic regulation. However, joint effects of essential and non-essential metals on glucose concentrations during pregnancy are unclear. This study explored the joint associations of pregnancy exposures to essential (copper, magnesium, manganese, selenium, zinc) and non-essential (arsenic, barium, cadmium, cesium, lead, mercury) metals with gestational glucose concentrations using 1,311 women enrolled 1999–2002 in Project Viva, a Boston, MA-area pregnancy cohort. The study measured erythrocyte metal concentrations from 1st trimester blood samples and used glucose concentrations measured 1 h after non-fasting 50-gram glucose challenge tests (GCT) from clinical gestational diabetes screening at 26–28 weeks gestation. Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation were applied to model the associations of metal mixtures—including their interactions—with glucose concentrations post-GCT. We tested for reproducibility of BKMR results using generalized additive models. The BKMR model showed an inverse U-shaped association for barium and a linear inverse association for mercury. Specifically, estimated mean glucose concentrations were highest around 75th percentile of barium concentrations [2.1 (95% confidence interval: −0.2, 4.4) mg/dL higher comparing to the 25th percentile], and each interquartile range increase of erythrocyte mercury was associated with 1.9 mg/dL lower mean glucose concentrations (95% credible interval: −4.2, 0.4). Quantile g-computation showed joint associations of all metals, essential-metals, and non-essential metals on gestational glucose concentrations were all null, however, we observed evidences of interaction for barium and lead. Overall, we found early pregnancy barium and mercury erythrocytic concentrations were associated with altered post-load glucose concentrations in later pregnancy, with potential interactions between barium and lead.

Reduced Birth Weight, Decreased Early-Phase Insulin Secretion, and Increased Glucose Concentrations after Oral Glucose Tolerance Test in Japanese Women Aged 20 Years with Family History of Type 2 Diabetes

Introduction We tested the hypothesis that family history of type 2 diabetes (FHD) is associated with reduced birth weight and reduced insulin secretion later in life. Materials and Methods Birth weight, body composition by whole-body dual-energy X-ray absorptiometry, and homeostasis model assessment-insulin resistance were compared between Japanese women aged 20 years with positive (n = 73) and negative (n = 258) FHD. A subsample of 153 women (57 with positive FHD) underwent a 75 g oral glucose tolerance test. Multivariate logistic regression analyses were used to identify the most important determinants of FHD. Results Women with positive as compared with negative FHD had lower birth weight (3132 ± 364 vs. 3238 ± 418 g, p = 0.04). However, the current fat mass index and trunk/leg fat ratio, sophisticated measures of general and abdominal fat accumulation, respectively, did not differ. Women with positive FHD had a lower insulinogenic index (2.4 ± 7.3 vs. 6.2 ± 16, p = 0.007) and higher area under the glucose curve (217 ± 47 vs. 198 ± 36 mg/dL/2 h, p = 0.006). However, fasting and postload insulinemia, homeostasis model assessment-insulin resistance, and Matsuda index did not differ. In multivariate logistic regression analysis, birth weight was marginally associated with FHD (odds ratio, 0.999; 95% confidential interval, 0.98-1.00000; p = 0.0509). Conclusions FHD was associated not only with reduced birth weight but also with decreased early-phase insulin secretion and increased postload glucose concentrations in Japanese women aged 20 years. These findings may be in keeping with the fetal insulin hypothesis and provide some evidence that FHD can alter size at birth, probably through genetic and shared environmental components, which consequently resulted in decreased early-phase insulin secretion and increased glucose excursion in the early twenties. FHD was not related to sophisticated measures of general and abdominal adiposity and insulin resistance/sensitivity.

Improving Glucose Homeostasis after Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism with Co-Existing Prediabetes.

We have previously described increased fasting plasma glucose levels in patients with normocalcemic primary hyperparathyroidism (NPHPT) and co-existing prediabetes, compared to prediabetes per se. This study evaluated the effect of parathyroidectomy (PTx) (Group A), versus conservative follow-up (Group B), in a small cohort of patients with co-existing NPHPT and prediabetes. Sixteen patients were categorized in each group. Glycemic parameters (levels of fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), and fasting insulin (fIns)), the homeostasis model assessment for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR), and a 75-g oral glucose tolerance test were evaluated at baseline and after 32 weeks for both groups. Measurements at baseline were not significantly different between Groups A and B, respectively: fGlu (119.4 ± 2.8 vs. 118.2 ± 1.8 mg/dL, p = 0.451), HbA1c (5.84 ± 0.3 %vs. 5.86 ± 0.4%, p = 0.411), HOMA-IR (3.1 ± 1.2 vs. 2.9 ± 0.2, p = 0.213), HOMA-B (112.9 ± 31.8 vs. 116.9 ± 21.0%, p = 0.312), fIns (11.0 ± 2.3 vs. 12.8 ± 1.4 μIU/mL, p = 0.731), and 2-h post-load glucose concentrations (163.2 ± 3.2 vs. 167.2 ± 3.2 mg/dL, p = 0.371). fGlu levels demonstrated a positive correlation with PTH concentrations for both groups (Group A, rho = 0.374, p = 0.005, and Group B, rho = 0.359, p = 0.008). At the end of follow-up, Group A demonstrated significant improvements after PTx compared to the baseline: fGlu ((119.4 ± 2.8 vs. 111.2 ± 1.9 mg/dL, p = 0.021) (−8.2 ± 0.6 mg/dL)), and 2-h post-load glucose concentrations ((163.2 ± 3.2 vs. 144.4 ± 3.2 mg/dL, p = 0.041), (−18.8 ± 0.3 mg/dL)). For Group B, results demonstrated non-significant differences: fGlu ((118.2 ± 1.8 vs. 117.6 ± 2.3 mg/dL, p = 0.031), (−0.6 ± 0.2 mg/dL)), and 2-h post-load glucose concentrations ((167.2 ± 2.7 vs. 176.2 ± 3.2 mg/dL, p = 0.781), (+9.0 ± 0.8 mg/dL)). We conclude that PTx for individuals with NPHPT and prediabetes may improve their glucose homeostasis when compared with conservative follow-up, after 8 months of follow-up.

Salivary Alpha-Amylase Activity in Relation to Cardiometabolic Status in Japanese Adults without History of Cardiovascular Disease.

Aims: Stress is known to be a potential contributor to the development of diabetes and hypertension. However, the biological mechanisms underlying the association between cardiometabolic risk markers and the biological stress response have not yet been determined. Therefore, we examined salivary alpha-amylase and heart rate variability in relation to cardiometabolic status in a sample of healthy Japanese men and women. Methods: Participants (473 men and 1,029 women aged 30-84) underwent a 75 g oral glucose tolerance test after a 10-hr fast. The homeostasis model assessment index for insulin resistance was based on fasting and 2-hr postload glucose and insulin concentrations. Sitting blood pressure was measured twice after rest. A saliva sample was collected in the morning and salivary alpha-amylase was assayed. A 5-min heart rate variability recording was evaluated using time-domain indices of standard deviations of normal-to-normal intervals and root mean square of successive differences. Multivariate linear regression models were used to estimate associations between salivary alpha-amylase and each outcome measure. Results: Salivary alpha-amylase was associated with fasting glucose (β=0.008; 95% CI=0.002, 0.014), 2-hr postload glucose (β=0.023; 95% CI=0.004, 0.041), homeostasis model assessment index for insulin resistance (β=0.032; 95%CI=0.000, 0.064), systolic (β=1.603; 95% CI=0.479, 2.726) and diastolic (β=0.906; 95% CI=0.212, 1.600) blood pressures among women. These associations remained significant after further adjustment for heart rate variability measures. Conclusions: The elevation of salivary alpha-amylase may reflect a dysfunction of the sympathetic nervous system associated with cardiometabolic abnormalities in women.

Could the performance of oral glucose tolerance test contribute to the brain health-focused care in multiple sclerosis?

BackgroundIt has not been clarified yet if persons with multiple sclerosis (MS) are at increased risk to develop glucose metabolism dysregulation. The aims of the present study were to evaluate glucose metabolism characteristics in persons with MS and to compare it to the healthy individuals; to examine the association of glucose metabolism with the level of disability and its progression. MethodsThe study enrolled 78 patients with MS and 26, comparable for age, gender and body mass index (BMI), healthy controls (HC). Disability and its progression were evaluated by the Expanded Disability Status Scale (EDSS) score, progression index (PI) and multiple sclerosis severity score (MSSS). All participants performed an oral glucose tolerance test (OGTT). Insulin and lipid parameters were analyzed. ResultsFasting glucose concentrations (5.3±0.7 in MS patients vs. 4.5±0.9 mmol/L in HC, p=0.001) and 2 hour post-load glucose concentrations were statistically significantly higher in MS patients compared with controls. Glucose levels at all different time points during OGTT, baseline insulin, Homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol and LDL were statistically significantly (p<0.05) associated with MS, in univariable logistic regression analysis. Glucose level at 120’ was independently associated with MS (OR=3.937, 95% CI 1.178-13.159, p=0.026), in the multivariable model. The prevalence of IR was 64.1% in the MS group compared to 30.8% in the control group (p=0.008), based on HOMA-IR. EDSS and Multiple sclerosis severity score (MSSS) were associated with glucose levels at different time points (p<0.05). According to the ROC analysis, best cut-off value for HOMA-IR is 2.3, providing both sensitivity and specificity of 66.7% in discriminating persons with MS and HC. ConclusionOur results demonstrate the presence of higher prevalence of IR in MS patients compared to healthy individuals, and strong association between impaired glucose metabolism and disability. Finally, it has to be emphasized that further studies are warranted to confirm our findings implicating that MS patients have significantly higher risk of impaired glucose metabolism, which could suggest the potential importance of the performance of OGTT in patients with this disorder.

Increased parathyroid hormone is associated with higher fasting glucose in individuals with normocalcemic primary hyperparathyroidism and prediabetes: A pilot study

AimsThis pilot study aimed to evaluate differences in glycemic parameters between patients with prediabetes and normocalcemic primary hyperparathyroidism (NPHPT) and controls with prediabetes and normal parathyroid hormone (PTH) and calcium concentrations. Methods20 patients with NPHPT and prediabetes and 42 age-, gender-, and body mass index-matched controls with prediabetes were included. Glycemic parameters [fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), fasting insulin (fIns)] were evaluated. Homeostasis Model Assessment was used for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR). Participants underwent a 75-g oral glucose tolerance test. ResultsHbA1c (5.9 ± 0.0 vs 5.9 ± 0.0%, p = 0.44), HOMA-IR (3.7 ± 1.2 vs 2.9 ± 0.2, p = 0.48), HOMA-B (117.8 ± 31.8 vs 146.9 ± 22.0%, p = 0.14), fIns (14.0 ± 4.3 vs 12.2 ± 1.1 μIU/ml, p = 0.53) and 2-hour post-load glucose concentrations (157.2 ± 2.2 vs 152.2 ± 2.0 mg/dl, p = 0.07), were nondifferent in the two groups. Higher fGlu levels were evident in the NPHPT, compared to the control group (105.6 ± 2.8 vs 98.2 ± 1.8 mg/dl, p = 0.01). fGlu demonstrated a positive correlation with PTH concentrations (rho = 0.374, p = 0.005). ConclusionsIndividuals with NPHPT and prediabetes present an unfavorable glycemic profile compared to age-matched people with prediabetes, suggesting a direct adverse effect of elevated PTH on glucose homeostasis.

Aerobic Exercise Training Improves Cerebral Blood Flow and Executive Function: A Randomized, Controlled Cross-Over Trial in Sedentary Older Men.

BackgroundPhysical activity may attenuate age-related cognitive decline by improving cerebrovascular function. The aim of this study was therefore to investigate effects of aerobic exercise training on cerebral blood flow (CBF), which is a sensitive physiological marker of cerebrovascular function, in sedentary older men.MethodsSeventeen apparently healthy men, aged 60–70 years and with a BMI between 25 and 35 kg/m2, were included in a randomized, controlled cross-over trial. Study participants were randomly allocated to a fully-supervised, progressive, aerobic exercise training or no-exercise control period for 8 weeks, separated by a 12-week wash-out period. Measurements at the end of each period included aerobic fitness evaluated using peak oxygen consumption during incremental exercise (VO2peak), CBF measured with pseudo-continuous arterial spin labeling magnetic resonance imaging, and post-load glucose responses determined using an oral glucose tolerance test (OGTT). Furthermore, cognitive performance was assessed in the domains of executive function, memory, and psychomotor speed.ResultsVO2peak significantly increased following aerobic exercise training compared to no-exercise control by 262 ± 236 mL (P < 0.001). CBF was increased by 27% bilaterally in the frontal lobe, particularly the subcallosal and anterior cingulate gyrus (cluster volume: 1008 mm3; P < 0.05), while CBF was reduced by 19% in the right medial temporal lobe, mainly temporal fusiform gyrus (cluster volume: 408 mm3; P < 0.05). Mean post-load glucose concentrations determined using an OGTT decreased by 0.33 ± 0.63 mmol/L (P = 0.049). Furthermore, executive function improved as the latency of response was reduced by 5% (P = 0.034), but no changes were observed in memory or psychomotor speed.ConclusionAerobic exercise training improves regional CBF in sedentary older men. These changes in CBF may underlie exercise-induced beneficial effects on executive function, which could be partly mediated by improvements in glucose metabolism. This clinical trial is registered on ClinicalTrials.gov as NCT03272061.

Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease

We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity. We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2 h post-load glucose concentrations. Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6% vs. 11%, p = 0.02). In particular, 124 (20.6%) children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8% (n = 119) satisfying the diagnostic criteria for prediabetes and 0.8% (n = 5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a nearly 2.2-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjustedodds ratio 2.19; 95% CI 1.47-3.29; p <0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjustedodds ratio 1.69, 95% CI 1.06-2.69, p = 0.032), and the PNPLA3 rs738409 polymorphism. Both this PNPLA3 polymorphism and waist circumference were strongly associated with NASH. Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH. Children with biopsy-proven non-alcoholic fatty liver disease (NAFLD) have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of the progressive form of disease, non-alcoholic steatohepatitis, than those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with non-alcoholic steatohepatitis.

GIP and GLP-1: Stepsiblings Rather Than Monozygotic Twins Within the Incretin Family.

The importance of the incretin effect for the postprandial augmentation of insulin released has long been recognized (1). However, there has been a long-standing controversy as to the relative importance of the various gastrointestinal hormones in mediating this effect. While earlier studies suggested a contribution of gastrin, secretin, and cholecystokinin (2), it later became obvious that in humans, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are the predominant incretin hormones (1). Which of the two incretins is the most relevant one is still a matter of debate. Gasbjerg et al. (3) performed studies in healthy human subjects receiving oral glucose loads of 75 g in the fasting state on four different days. The known incretin hormones, GIP and GLP-1, which are secreted in response to glucose administration/absorption, were antagonized with the established peptide receptor antagonist exendin(9-39), blocking the stimulation of GLP-1 receptors, or with the novel GIP receptor antagonist, GIP(3-30)amide, a naturally occurring fragment of intact GIP (full sequence 1–42), which has recently been characterized as a specific GIP receptor antagonist for use in human studies (4). A similar GIP receptor antagonist, GIP(7-30)amide, had previously been used in animal studies but had not been validated for human experiments (5). These incretin receptor antagonists were compared with placebo and used alone and in combination. The result was a slight rise in postload glucose concentrations and a minor reduction in insulin secretory responses, when the GLP-1 receptor was blocked, and a substantial rise in glycemic excursions after the glucose load and a more pronounced reduction in insulin secretory responses, when the recently validated GIP antagonist GIP(3-30)amide was administered at an approximately 1,000-fold excess (∼60 nmol/L) over endogenous peak GIP concentrations (∼60 pmol/L). The combination of exendin(9-39) and GIP(3-30)amide further raised plasma glucose and reduced insulin secretory responses over and above …

One-hour post-load plasma glucose predicts progression to prediabetes in a multi-ethnic cohort of obese youths.

One-hour post-load hyperglycaemia has been proposed as an independent predictor of type 2 diabetes in adults. We examined whether 1-hour plasma glucose (1hPG) during an oral glucose tolerance test (OGTT) can predict changes in the glucose tolerance status of a multi-ethnic cohort of youths with normal glucose tolerance (NGT). A total of 202 obese youths with NGT (33.7% Caucasian, 31.1% Hispanic, 32.2% African American) underwent a 3-hour OGTT at baseline and after a 2-year follow-up period. Whole-body insulin sensitivity, insulin secretion, β-cell function and insulin clearance were estimated by modeling plasma glucose, insulin and C-peptide levels. Obese youths with 1hPG ≥7.4 mmol/L (or 133 mg/dL; n = 83) exhibited higher body mass index (BMI), plasma triglycerides and fasting and post-load glucose concentrations than individuals with 1hPG <7.4 mmol/L. Also, 1hPG ≥7.4 mmol/L was associated with a lower disposition index (DI) (P < 0.0001) and with alterations in whole-body insulin sensitivity, β-cell function and insulin clearance. Adolescents with 1hPG ≥7.4 mmol/L were approximately three times more likely to develop prediabetes (ie, impaired glucose tolerance and/or impaired fasting glucose) over time (OR, 2.92 [1.22-6.98]; P = 0.02), independent of age, sex, race/ethnicity, BMI, insulin sensitivity, DI and plasma glucose concentrations. No differences emerged in the risk of prediabetes related to 1-hour hyperglycaemia among different ethnic groups. A plasma glucose concentration ≥ 7.4 mmol/L at 1 hour during an OGTT is associated with a worse clinical and metabolic phenotype and may be an independent predictor of progression to prediabetes in obese youths with NGT.

The role of one-hour post-load hyperglycemia in prediction and prevention of type 2 diabetes

One-hour post-load glucose concentration (1hPG) ≥155 mg/dl (8.6 mmol/L) in individuals with normal glucose tolerance (NGT) was correlated with increased risk for type 2 mellitus. This paper is the Chinese translation One-hour post-load hyperglycemia: implications for prediction and prevention of type 2 diabetes , published on The Journal of Clinical Endocrinology & Metabolism [Fiorentino TV, Marini MA, Succurro E, et al. J Clin Endocrinol Metab, 2018, 103(9): 3131-3143] after obtaining the copyright of the original journal. In this review, the authors analyzed the role of 1hPG measurement in prediction of type 2 and cardiovascular disease. They used MEDLINE and included all English studies published up to February 2018 in peer-reviewed journals that examined the relationship between 1hPG and diabetes, cardio-metabolic alterations, organ damage, and cardiovascular disease. The results showed that although 1hPG was not adopted by American Diabetes Association for identifying high-risk individuals, the available evidence indicated that, among subjects with NGT, a value of 1hPG≥155 mg/dl is helpful to identify those at increased risk of type 2 and cardiovascular disease. (Chin J Endocrinol Metab, 2018, 34: 1060-1066) Key words: 1-h post-load glucose concentration; Diabetes mellitus, type 2; Blood-derived biomarkers