Chronic kidney disease is associated with attenuated plasma metabolome response to oral glucose tolerance testing

Chronic kidney disease (CKD), a major public health problem, is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of the response to oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD. Using targeted metabolic profiling, we examined plasma metabolome in 41 moderate-to-severe non-diabetic CKD patients with estimated glomerular filtration rate (eGFR)<60ml/min per 1.73m2 (38.9+-12.7) and 20 healthy controls with normal eGFR (87.2+-17.7) before and after 2h of 75g oral glucose load. Compared to controls, CKD participants had higher lactate: pyruvate (L:P) ratio both at fasting and after oral glucose challenge. Total energy production estimated through GTP:GDP ratio was impaired during OGTT despite similar fasting GTP:GDP ratio. CKD group had sustained elevation of vitamin B family members, TCA cycle metabolites, and purine nucleotides in response to glucose challenge. Metabolic profiling in response to OGTT suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into insulin sensitizers in patients with non-diabetic CKD and their impact on energy metabolism.

Perinatal Outcomes in Obese Women with One Abnormal Value on 3-Hour Oral Glucose Tolerance Test

Objective This study aimed to determine if one abnormal value of four on the diagnostic 3-hour oral glucose tolerance test (OGTT) is associated with adverse perinatal outcomes in obese women. Study Design This is a secondary analysis of a prospective study of nulliparous women in eight geographic regions. Women with body mass index <30 kg/m2 and pregestational diabetes mellitus (GDM) were excluded. Four groups were compared: (1) normal 50-g 1-hour glucose screen, (2) elevated 1-hour glucose screen with normal 100-g 3-hour diagnostic OGTT, (3) elevated 1-hour glucose screen and one of four abnormal values on 3-hour OGTT, and (4) GDM. Using multivariable logistic regression adjusting for covariates, the women in the groups with dysglycemia were compared with those in the normal screen group for maternal and neonatal outcomes. Results Among 1,713 obese women, 1,418 (82.8%) had a normal 1-hour glucose screen, 125 (7.3%) had a normal 3-hour diagnostic OGTT, 72 (4.2%) had one abnormal value on their diagnostic OGTT, and 98 (5.7%) were diagnosed with GDM. The one abnormal value group had increased risk of large for gestational age (LGA) neonates (adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI]: 1.31–3.82), cesarean delivery (aOR = 2.19, 95% CI: 1.34–3.58), and hypertensive disorders of pregnancy (aOR = 2.19, 95% CI: 1.32–3.63) compared with normal screens. The one abnormal value group also had an increased risk of preterm birth <37 weeks (aOR = 2.63, 95% CI: 1.43–4.84), neonatal respiratory support (aOR = 2.38, 95% CI: 1.23–4.60), and neonatal hyperbilirubinemia (aOR = 2.00, 95% CI: 1.08–3.71). There was no association between one abnormal value with shoulder dystocia and neonatal hypoglycemia. Conclusion For obese women, one abnormal value on the 3-hour OGTT confers increased perinatal adverse outcomes. These women should be studied further to determine if nutrition counseling and closer fetal monitoring improve outcomes even in the absence of a diagnosis of GDM. Key Points

Diabetology for primary health care – the use of metformin in the treatment of prediabetes, primary prevention and secondary prevention in type 2 diabetes

The 2021 guidelines on the management of diabetes by the Polish Diabetes Association introduce the new criterion for the diagnosis of diabetes – percentage of glycated hemoglobin HbA1c > 6.5%. This is important, especially now, during the COVID-19 epidemic, for patients with diagnosed pre-diabetes who are already using metformin, as it allows to release the need for an oral glucose tolerance test. The article describes the principles of using metformin in the prevention of type 2 diabetes.

Use of Oral Glucose Tolerance Testing and HbA1c At 6-14 Gestational Weeks to Predict Gestational Diabetes Mellitus In High-Risk Women

Objective:To study the prediction of gestational diabetes mellitus (GDM) in high-risk pregnant women by testing the 1-hour (1hPG) and 2-hour plasma glucose (2hPG) after an oral glucose tolerance test and the glycated hemoglobin (HbA1c) in early pregnancy (6-14 weeks).Methodology:We recruited 1311 pregnant women at high risk for diabetes from the Obstetrics Clinic of Daxing District People's Hospital between June 2017 and December 2019. Fasting blood glucose (FPG) and HbA1c were tested and a 75 g oral glucose tolerance test (OGTT) with 1-hour blood glucose (1hPG) and 2-hour blood glucose (2hPG) was performed during the first trimester of pregnancy. The women were seen at 24-28 weeks to follow-up for GDM. We calculated the receiver operating characteristic (ROC) and the area under the ROC curve (AUC) to determine the predictive values for early pregnancy FPG, 1hPG, 2hPG, and HbA1c for GDM in high-risk pregnant women.Results:The prevalence of pregestational diabetes mellitus among pregnant women at high risk of diabetes was 5.6%, and GDM was 24.7%. The AUCs for the predictive value of FPG, 1hPG, 2hPG, and HbA1c in high-risk pregnant women were 0.64, 0.76, 0.71, and 0.67, respectively. The AUC for 1hPG prediction of GDM in high-risk pregnant women is greater than FPG, 2hPG, and HbA1c. All differences were statistically significant.Conclusion:FPG, 1hPG, 2hPG, and HbA1c measured in the first trimester pregnancy of high-risk women are significant predictors of GDM. 1hPG was the most significant predictive value for GDM in high-risk pregnant women.

Early Versus Routine Oral Glucose Tolerance Test in Women With Intermediate Hyperglycemia at First Prenatal Visit: A Retrospective Cohort Study in China

Background and ObjectivesIntermediate hyperglycemia in the first half of pregnancy, defined as a fasting plasma glucose level between 5.1- 6.9 mM, increases the risk of gestational diabetes mellitus, but clinical evidence for further management is lacking. We aim to evaluate the effectiveness of an early oral glucose tolerance test (OGTT) followed by the identification of intermediate hyperglycemia on pregnancy outcomes in real world setting.Subjects and MethodsA retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, between 2013 and 2017. Women with intermediate hyperglycemia at the first prenatal visit were identified and underwent an immediate (within one week) or a routine OGTT (24-28 gw) according to their wishes and received nutrition and exercise advice. Women diagnosed of gestational diabetes (GDM) were managed by standard interventions. Primary outcome was larger for gestational age (LGA). Secondary outcomes were primary cesarean delivery, preterm birth, shoulder dystocia or forceps delivery, preeclampsia, neonatal hypoglycemia, hyperbilirubinemia, and low Apgar score. Logistic regressions with or without a further propensity score-matched analysis were performed.ResultsAmong 42406 women involved, 1104 (2.6%) with intermediate hyperglycemia at the first prenatal visit were identified, of whom 176 (15.9%) underwent an early OGTT and 741 (67.1%) received a routine OGTT. Logistic regression showed that an early OGTT was not significantly associated with an altered risk of LGA (adjusted OR 1.13, 95% CI 0.73-1.75) but was related to an increased odds for neonatal hyperbilirubinemia (adjusted OR 2.89; 95% CI 1.55-5.37). No significant associations were observed for other secondary outcomes. These trends remained consistent in propensity score-matched models.ConclusionsOur data from a real-world setting did not support that an early OGTT among women with intermediate hyperglycemia at the first prenatal visit improved pregnancy outcomes.

Glucose Concentrations from Continuous Glucose Monitoring Devices Compared to Those from Blood Plasma during an Oral Glucose Tolerance Test in Healthy Young Adults

Continuous glucose monitoring devices measure glucose in interstitial fluid. The devices are effective when used by patients with type 1 and 2 diabetes but are increasingly being used by researchers who are interested in the effects of various behaviours of glucose concentrations in healthy participants. Despite their more frequent application in this setting, the devices have not yet been validated for use under such conditions. A total of 124 healthy participants were recruited to a ten-day laboratory study. Each participant underwent four oral glucose tolerance tests, and a total of 3315 out of a possible 4960 paired samples were included in the final analysis. Bland–Altman plots and mean absolute relative differences were used to determine the agreement between the two methods. Bland–Altman analyses revealed that the continuous glucose monitoring devices had proportional bias (R = 0.028, p < 0.001) and a mean bias of −0.048 mmol/L, and device measurements were more variable as glucose concentrations increased. Ninety-nine per cent of paired values were in Zones A and B of the Parkes Error Grid plot, and there was an overall mean absolute relative difference of 16.2% (±15.8%). There was variability in the continuous glucose monitoring devices, and this variability was higher when glucose concentrations were higher. If researchers were to use continuous glucose monitoring devices to measure glucose concentrations during an oral glucose tolerance test in healthy participants, this variability would need to be considered.