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Dietary glucose in excess is stored in the liver in the form of glycogen. As opposed to direct conversion of glucose into glycogen, the hypothesis of the postprandial lactate shuttle (PLS) proposes that dietary glucose uptake is metabolized to lactate in the gut, thereby being transferred to the liver for glycogen storage. In the present study, we provide evidence of a PLS in young healthy men and women. Overnight fasted participants underwent an oral glucose tolerance test, and arterialized lactate concentration and rate of appearance were determined. The concentration of lactate in the blood rose before the concentration of glucose, thus providing evidence of an enteric PLS. Secondary increments in the concentration of lactate in the blood and its rate of appearance coincided with those of glucose, which indicates the presence of a larger, secondary, systemic PLS phase driven by hepatic glucose release. The present study challenges the notion that lactate production is the result of hypoxia in skeletal muscles, because our work indicates that glycolysis proceeds to lactate in fully aerobic tissues and dietary carbohydrate is processed via lactate shuttling. Our study proposes that, in humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolism.

(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.

Objective Cystic Fibrosis Foundation guidelines recommend annual diabetes screening by oral glucose tolerance test (OGTT) in pediatric patients with cystic fibrosis (CF) starting at the age of 10 years. Adherence to these guidelines proves to be challenging, and the nationwide screening rates are still considered suboptimal. The aim of this study was to assess and improve the screening rates at our large pediatric center. Methods A 4-year retrospective audit of OGTT completion among pediatric patients with CF of age ≥10 years who are not yet diagnosed with diabetes was conducted. A collaborative working group was formed to identify the barriers to screening and formulate a quality improvement plan, which was monitored and evaluated for a 9-month period. Results Diabetes screening rates determined by OGTT completion at our center showed a gradual decline during the COVID-19 pandemic from 2019 to 2022. Following the implementation of the quality improvement plan during the summer of 2023, there was a marked increase in OGTT ordering compliance by providers as well as test completion by patients. Notably, the fractional OGTT completion rate rose from 45% during the preintervention phase (January-April 2023) to 70% during the postintervention phase (May-September 2023). Conclusion Diabetes screening in pediatric patients with CF can be effectively improved by refining practices related to patient experience, care coordination, and laboratory testing strategies. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes is associated with adverse outcomes such as preterm birth (<37 weeks). However, there is no international consensus on screening criteria or diagnostic levels for gestational diabetes, and it is unknown whether body mass index (BMI) or obesity modifies the relation between glucose level and preterm birth. Methods: We studied a pregnancy cohort restricted to two Danish regions from the linked Danish Medical Birth Register to study associations between glucose measurements from the 2-hour postload 75-g oral glucose tolerance test (one-step approach) and preterm birth from 2004 to 2018. In Denmark, gestational diabetes screening is a targeted strategy for mothers with identified risk factors. We used Poisson regression to estimate rate ratios (RR) of preterm birth with z-standardized glucose measurements. We assessed effect measure modification by stratifying analyses and testing for heterogeneity. Results: Among 11,337 pregnancies (6.2% delivered preterm), we observed an adjusted preterm birth RR of 1.2 (95% confidence interval [CI] = 1.1, 1.3) for a one-standard deviation glucose increase of 1.4 mmol/l from the mean of 6.7 mmol/l. There was evidence for effect measure modification by obesity, for example, adjusted RR for nonobese (BMI, <30): 1.2 (95% CI = 1.1, 1.3) versus obese (BMI, ≥30): 1.3 (95% CI = 1.2-1.5), P = 0.05 for heterogeneity. Conclusion: Among mothers screened for gestational diabetes, increased glucose levels, even those below the diagnostic level for gestational diabetes in Denmark, were associated with increased preterm birth risk. Obesity (BMI, ≥30) may be an effect measure modifier, not just a confounder, of the relation between blood glucose and preterm birth risk. [ABSTRACT FROM AUTHOR]

Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study. Pediatric patients with an OGTT indication who attended the Diabetes Unit between December 2020 and September 2021 were recruited for this prospective observational study. During the functional test, glycaemia was immediately measured in venous blood using two glucometers (unconnected and connected) and sent to the central laboratory. The study included 98 patients. There was a high correlation between the glucometers and the central laboratory (Pearson correlation coefficient=0.912 and 0.950, for unconnected and connected glucometer, respectively). The median OGTT turnaround time (TAT) was significantly decreased (connected glucometer: 2.02 h [interquartile range, 2.00–2.07], central laboratory: 11.63 h [6.09–25.80]), with similar overall cost. The diagnostic concordance between connected glucometer and the central laboratory was 71.1 % (95 % confidence interval (CI) 61.5–79.2). The clinical decision would have been the same in the 92.8 % of the cases, but treatment would have not been indicated in 4 patients (4.1 %). POCT glucometers have demonstrated a high correlation and an acceptable diagnostic concordance with the central laboratory during an OGTT, as well the connected device offers a significant decrease in TAT, without increasing costs. However, as severe clinical impact could happen, POCT glucometers may not be used for diagnosis yet. [ABSTRACT FROM AUTHOR]

Background/Objective: Diet is a risk factor for gestational diabetes mellitus (GDM). There are few studies on women's diet and glucose tolerance test (GTT) results during pregnancy. The objective of this study was to evaluate the relationship between one's previous diet and the number of abnormal values on the diagnostic GTT in women with GDM. We hypothesized that there would be an inverse relation between antioxidant micronutrient consumption and the number of abnormal GTT values. Methods: This cross-sectional study included 60 women diagnosed with GDM (2-h, 75 g-GTT), divided in two groups as follows: 1 abnormal glucose value and 2–3 abnormal values. Shortly after the diagnosis, participants answered a validated food frequency questionnaire to assess their food consumption in the last 6 months. The Mann–Whitney test was used to compare the dietary intake of the participants in the two groups. Results: The participant characteristics were similar. The median intake of total calories, carbohydrates, lipids, and proteins did not differ significantly between groups. Participants with 1 abnormal GTT value had significantly higher intakes of fiber (11.9 vs. 11.0 g/day p = 0.049), vitamin D (40.6 vs. 40.4 mcg/day p = 0.049), and vitamin C (180.0 vs. 151.0 mg/day p = 0.008) than those with 2–3 abnormal values. Conclusions: Our results suggest a possible association between the consumption of fiber and antioxidant micronutrients and the number of abnormal GTT values. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that residents of higher elevations have lower glucose levels. Our objective in this study is to determine the basal and postprandial glucose levels in apparently healthy permanent residents of the miner population center of La Rinconada located 5100 meters (m) above sea level. Method: Forty male permanent residents of the Rinconada miner population center were studied. The oral glucose tolerance test was used to evaluate basal and postprandial glycemia levels at 1, 2, and 3 h. Results: The individuals had a mean age of 43.95 ± 8.54 years. Basal glycemia in subjects without excessive erythrocytosis (EE) was 73.3 ± 7.9 mg/dL, while levels in patients with EE were 57.98 ± 7.38 mg/dL. In the postprandial period, at 1 h after oral glucose overload, a mean value of 76.35 ± 13.53 mg/dL was observed in subjects with EE compared to 94.68 ± 9.98 mg/dL in subjects without EE. After 2 h, subjects with EE had a glycemia level of 72.91 ± 9.17 mg/dL EE compared to 90.73 ± 13.86 mg/dL without EE. At 3 h, the average glycemia level in subjects with EE was 70.77 ± 8.73 mg/dL compared to 87.79 ± 14.16 mg/dL in those without EE. Conclusion: These findings suggest that under hypoxic conditions, glycemia levels are lower in both subjects with and without EE, having obtained lower levels in subjects with EE in relation to those with normal values of Hb and Hct. The results of this study indicate that in the conditions of severe hypoxia, blood glucose levels are below the values considered normal for sea level. [ABSTRACT FROM AUTHOR]

ObjectiveChronic kidney disease (CKD) is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD.MethodsUsing targeted metabolic profiling, we studied the plasma metabolome response in 41 moderate-to-severe nondiabetic CKD patients and 20 healthy controls at fasting and 2 hours after an oral glucose load. We used linear mixed modeling with random intercepts, adjusting for age, gender, race/ethnicity, body weight, and batch to assess heterogeneity in response to OGTT by CKD status.ResultsMean estimated glomerular filtration rate among CKD participants was 38.9 ± 12.7 mL/min per 1.73 m2 compared to 87.2 ± 17.7 mL/min per 1.73 m2 among controls. Glucose ingestion induced an anabolic response resulting in increased glycolysis products and a reduction in a wide range of metabolites including amino acids, tricarboxylic acid cycle intermediates, and purine nucleotides compared to fasting. Participants with CKD demonstrated a blunted anabolic response to OGTT evidenced by significant changes in 13 metabolites compared to controls. The attenuated metabolome response predominant involved mitochondrial energy metabolism, vitamin B family, and purine nucleotides. Compared to controls, CKD participants had elevated lactate:pyruvate (L:P) ratio and decreased guanosine diphosphate:guanosine triphosphate ratio during OGTT.ConclusionMetabolic profiling of OGTT response suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into the impact of insulin sensitizers and mitochondrial targeted therapeutics on energy metabolism in patients with nondiabetic CKD.

Background: There is currently a scarcity of population-based records related to the prevalence of gestational diabetes mellitus (GDM) in India. There were various recommendations for screening and diagnostic tests for GDM, and no uniform standard has yet been established. Hence, a comparative study was conducted to assess the usefulness of the glucose challenge test (GCT) and fasting blood glucose (FBG)/post-prandial blood glucose (PPBG) test for the screening of GDM in pregnant women attending the prenatal clinic outpatient department. Methods: This is a comparative observational study involving 300 apparently normal pregnant who were randomly allocated to GCT and FBG/PPBG cohorts of 150 each. The tests were performed at 4 intervals: 8 to 10 weeks, 16 to 20 weeks, 24 to 28 weeks, and 32 to 36 weeks. All diagnosed GDM cases were appropriately handled. Results: Gestational diabetes mellitus was seen in 2.67% of the FBG/PPBG cohort and 5.34% of the GCT cohort. The GCT test identified 25% of GDM subjects before 24 weeks of gestation, 50% in 24 and 28 weeks, and 25% in > 32 weeks of gestation. The highest prevalence of GDM was noted in the 26–30-year age group. The highest prevalence of GDM was noted in pregnant women with ≥ 26 kg/m2 of body mass index (BMI), with 75% in the FBG/PPBG group and 62.5% in the GCT group. The incidence of GDM was higher in primigravida, 75% in the FBG/PPBG group, and 50% in the GCT group. A higher prevalence was observed in pregnant women of class 4 of socioeconomic status, and it was 75% in the FBG/PPBG group and 75% in the GCT group. A higher prevalence was noted in those with higher secondary education. The majority of GDM cases gave birth at term by labor, and there were no assisted vaginal births in this group. Moreover, 75% of GDM cases in the FBG/PPBG cohort and 62.5% of GDM cases in the GCT cohort had Caesarean section. Besides, 50% of infants from GDM mothers in the FBG/PPBG cohort were hospitalized, while 12.75% were admitted in the GCT cohort. The birth weight of neonates from GDM mothers was 3.09 ± 0.5 kg, 3.11 ± 0.6 kg in normal mothers, 2.98 ± 0.6 kg in the FBG/PPBG cohort, and 2.9 ± 0.5 kg in the GCT cohort. Conclusion: Irrespective of the last meal, the GCT in all pregnant women is an effective and easy screening approach for 1-step screening for the early diagnosis of GDM for subsequent management at the early gestational pregnancy, which can minimize the adverse obstetric and perinatal outcomes.

Abstract Background Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. Methods We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. Results Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0–13.0%, I2 =96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0–16.0%, I2 = 99%]. Conclusions This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.

Abstract Background A variety of screening tools and criteria are used for the diagnosis of gestational diabetes mellitus (GDM). As a result, the prevalence rate of GDM varied from 4.41% to 57.90% among studies from Pakistan. Beside this disagreement, similar multi-centric studies, community surveys and pooled evidence were lacking from the country. Therefore, this first systematic review and meta-analysis aimed to measure the overall and subgroup pooled estimates of GDM and explore the methodological variations among studies for any inconsistency. Methods Using the PRISMA guidelines, seventy studies were identified from PubMed, ScienceDirect, Google Scholar and PakMediNet database. Of them, twenty-four relevant studies were considered for systematic review and nine eligible studies selected for meta-analysis. AXIS was used for measuring quality of reporting, I^2 statistics for heterogeneity among studies and subgroups, funnel plot for reporting potential publication bias and forest plot for presenting pooled estimates. Results The pooled sample of nine studies was 27,034 (126 – 12,450) pregnant women, of any gestational age, from all four provinces of Pakistan. Overall pooled estimate of GDM was 16.7% (95% CI 13.1 – 21.1). The highest subgroup pooled estimate of GDM observed in studies from Balochistan (35.8%), followed by Islamabad (23.9%), Khyber Pakhtunkhwa (17.2%), Sindh (13.2%), and Punjab (11.4%). The studies that adopted 75g 2-h OGTT had a little lower pooled estimate (16.3% vs. 17.3%); and that adopted diagnostic cut-off values [≥ 92 (F), ≥ 180 (1-h) and ≥ 153 (2-h)] had a greater pooled estimate (25.4% vs. 15.8%). The studies that adopted Carpenter criteria demonstrated the highest subgroup pooled estimate of GDM (26.3%), after that IADPSG criteria (25.4%), and ADA criteria (23.9%). Conclusions Along with poor quality of reporting, publishing in non-indexed journals and significant disagreement between studies, the prevalence rate of GDM is high in Pakistan. Consensus building among stakeholders for recommended screening methods; and continuous medical education of the physicians are much needed for a timely detection and treatment of GDM.

This study aimed to investigate the use of leptin as a marker for gestational diabetes by analyzing any correlation between serum leptin levels versus oral glucose tolerance tests (at 24 to 28 weeks of pregnancy) and increased body weight (during pregnancy). A total of 110 female cases (81 pregnant and 29 non-pregnant) were included in the study. The 81 pregnant cases were divided into 3 groups according to their oral glucose tolerance test results. A chi-square test was used for categorical variables. The distribution of numerical variables was tested with the Shapiro–Wilk test. ANOVA and a post-hoc Bonferroni test was used for parametric data. Kruskal–Wallis variance analysis was used for non-parametric data. The Mann–Whitney U-test was used for pairwise comparisons. Spearman correlation analysis and multivariate regression analysis were performed for the evaluation of the correlation analysis between the parameters. Oral glucose tolerance test results were compared with leptin levels with a cut-off value of 11.43 for leptin. The ROC curve demonstrated an 83.3% sensitivity and 72.1% specificity for leptin. Leptin may play a role in the pathophysiology of gestational diabetes mellitus. However, the relationship between leptin levels and maternal weight gain during pregnancy is still unknown. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. Methods: We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. Results: Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0–13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0–16.0%, I2 = 99%]. Conclusions: This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country. [ABSTRACT FROM AUTHOR]

Background: A variety of screening tools and criteria are used for the diagnosis of gestational diabetes mellitus (GDM). As a result, the prevalence rate of GDM varied from 4.41% to 57.90% among studies from Pakistan. Beside this disagreement, similar multi-centric studies, community surveys and pooled evidence were lacking from the country. Therefore, this first systematic review and meta-analysis aimed to measure the overall and subgroup pooled estimates of GDM and explore the methodological variations among studies for any inconsistency. Methods: Using the PRISMA guidelines, seventy studies were identified from PubMed, ScienceDirect, Google Scholar and PakMediNet database. Of them, twenty-four relevant studies were considered for systematic review and nine eligible studies selected for meta-analysis. AXIS was used for measuring quality of reporting, I^2 statistics for heterogeneity among studies and subgroups, funnel plot for reporting potential publication bias and forest plot for presenting pooled estimates. Results: The pooled sample of nine studies was 27,034 (126 – 12,450) pregnant women, of any gestational age, from all four provinces of Pakistan. Overall pooled estimate of GDM was 16.7% (95% CI 13.1 – 21.1). The highest subgroup pooled estimate of GDM observed in studies from Balochistan (35.8%), followed by Islamabad (23.9%), Khyber Pakhtunkhwa (17.2%), Sindh (13.2%), and Punjab (11.4%). The studies that adopted 75g 2-h OGTT had a little lower pooled estimate (16.3% vs. 17.3%); and that adopted diagnostic cut-off values [≥ 92 (F), ≥ 180 (1-h) and ≥ 153 (2-h)] had a greater pooled estimate (25.4% vs. 15.8%). The studies that adopted Carpenter criteria demonstrated the highest subgroup pooled estimate of GDM (26.3%), after that IADPSG criteria (25.4%), and ADA criteria (23.9%). Conclusions: Along with poor quality of reporting, publishing in non-indexed journals and significant disagreement between studies, the prevalence rate of GDM is high in Pakistan. Consensus building among stakeholders for recommended screening methods; and continuous medical education of the physicians are much needed for a timely detection and treatment of GDM. [ABSTRACT FROM AUTHOR]

Objective: To establish diagnostic criteria for the 75‐g 2‐h glucose tolerance test (GTT) to diagnose gestational diabetes and define the clinical entity of gestational hyperglycemia. Methods: A retrospective analysis was performed of the results from 500 patients who had a 75‐g 1‐h glucose challenge test (GCT) in early pregnancy as part of a two‐step approach to screening and testing for gestational diabetes. The selected cohort was considered to have normal islet β‐cell function, and upper glycemic levels of normal glucose tolerance in the third trimester were statistically calculated, taking the cutoff threshold values to be the diagnostic criteria for the 75‐g 2‐h GTT. Gestational hyperglycemia was diagnosed from the false‐positive GCT result when ≥8.0 mmol/L (144 mg/dL). Results: The diagnostic criteria for the 75‐g 2‐h GTT were calculated as follows: fasting plasma glucose ≥5.4 mmol/L (97 mg/dL); 1‐h plasma glucose ≥10.5 mmol/L (189 mg/dL); and 2‐h plasma glucose ≥8.4 mmol/L (151 mg/dL). The new criteria confirmed a prevalence of gestational diabetes of 11.1% and gestational hyperglycemia of 13.6% in the study population. Conclusion: Novel diagnostic criteria for the 75‐g 2‐h GTT were established by statistical analysis. This resulted in a more acceptable prevalence of gestational diabetes in our community and the false‐positive GCT allowed the detection of gestational hyperglycemia. Synopsis: Novel diagnostic criteria for the glucose tolerance test to diagnose gestational diabetes and gestational hyperglycemia have been established by statistical analysis. [ABSTRACT FROM AUTHOR]

Background: There is currently a scarcity of population-based records related to the prevalence of gestational diabetes mellitus (GDM) in India. There were various recommendations for screening and diagnostic tests for GDM, and no uniform standard has yet been established. Hence, a comparative study was conducted to assess the usefulness of the glucose challenge test (GCT) and fasting blood glucose (FBG)/post-prandial blood glucose (PPBG) test for the screening of GDM in pregnant women attending the prenatal clinic outpatient department. Methods: This is a comparative observational study involving 300 apparently normal pregnant who were randomly allocated to GCT and FBG/PPBG cohorts of 150 each. The tests were performed at 4 intervals: 8 to 10 weeks, 16 to 20 weeks, 24 to 28 weeks, and 32 to 36 weeks. All diagnosed GDM cases were appropriately handled. Results: Gestational diabetes mellitus was seen in 2.67% of the FBG/PPBG cohort and 5.34% of the GCT cohort. The GCT test identified 25% of GDM subjects before 24 weeks of gestation, 50% in 24 and 28 weeks, and 25% in > 32 weeks of gestation. The highest prevalence of GDM was noted in the 26–30-year age group. The highest prevalence of GDM was noted in pregnant women with ≥ 26 kg/m2 of body mass index (BMI), with 75% in the FBG/PPBG group and 62.5% in the GCT group. The incidence of GDM was higher in primigravida, 75% in the FBG/PPBG group, and 50% in the GCT group. A higher prevalence was observed in pregnant women of class 4 of socioeconomic status, and it was 75% in the FBG/PPBG group and 75% in the GCT group. A higher prevalence was noted in those with higher secondary education. The majority of GDM cases gave birth at term by labor, and there were no assisted vaginal births in this group. Moreover, 75% of GDM cases in the FBG/PPBG cohort and 62.5% of GDM cases in the GCT cohort had Caesarean section. Besides, 50% of infants from GDM mothers in the FBG/PPBG cohort were hospitalized, while 12.75% were admitted in the GCT cohort. The birth weight of neonates from GDM mothers was 3.09 ± 0.5 kg, 3.11 ± 0.6 kg in normal mothers, 2.98 ± 0.6 kg in the FBG/PPBG cohort, and 2.9 ± 0.5 kg in the GCT cohort. Conclusion: Irrespective of the last meal, the GCT in all pregnant women is an effective and easy screening approach for 1-step screening for the early diagnosis of GDM for subsequent management at the early gestational pregnancy, which can minimize the adverse obstetric and perinatal outcomes. [ABSTRACT FROM AUTHOR]

In this paper, we delve into the realm of mathematical modeling as a powerful theoretical tool to understand essential aspects of medical-biological phenomena. This study focuses on developing a mathematical model incorporating the incomplete I-function (IIF) and estimating glucose supply in the human bloodstream. The results of our investigations are far-reaching, revealing many exciting scenarios across the various parameters under investigation. These results are not only practical but can also play an essential role in the contexts of medical and biological fields.

BackgroundPrevious studies showed that residents of higher elevations have lower glucose levels. Our objective in this study is to determine the basal and postprandial glucose levels in apparently healthy permanent residents of the miner population center of La Rinconada located 5100 meters (m) above sea level.MethodForty male permanent residents of the Rinconada miner population center were studied. The oral glucose tolerance test was used to evaluate basal and postprandial glycemia levels at 1, 2, and 3 h.ResultsThe individuals had a mean age of 43.95 ± 8.54 years. Basal glycemia in subjects without excessive erythrocytosis (EE) was 73.3 ± 7.9 mg/dL, while levels in patients with EE were 57.98 ± 7.38 mg/dL. In the postprandial period, at 1 h after oral glucose overload, a mean value of 76.35 ± 13.53 mg/dL was observed in subjects with EE compared to 94.68 ± 9.98 mg/dL in subjects without EE. After 2 h, subjects with EE had a glycemia level of 72.91 ± 9.17 mg/dL EE compared to 90.73 ± 13.86 mg/dL without EE. At 3 h, the average glycemia level in subjects with EE was 70.77 ± 8.73 mg/dL compared to 87.79 ± 14.16 mg/dL in those without EE.ConclusionThese findings suggest that under hypoxic conditions, glycemia levels are lower in both subjects with and without EE, having obtained lower levels in subjects with EE in relation to those with normal values of Hb and Hct. The results of this study indicate that in the conditions of severe hypoxia, blood glucose levels are below the values considered normal for sea level.

Despite clinical guidelines do not recommend the use of point-of-care testing (POCT) glucometers for diagnostic purposes yet, the analytical performance is continuously improving. Thus, we evaluate the technical accuracy and clinical concordance of POCT glucometers during an oral glucose tolerance test (OGTT) in children for prediabetes and diabetes diagnosis in a comparison study.

IntroductionClinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors associated with completed postpartum diabetes screening (2-hour oral glucose tolerance test within 4-12 weeks postpartum), as recommended by the American Diabetes Association (ADA).Research design and methodsWithin the context of Gestational Diabetes' Effects on Moms (GEM), a pragmatic cluster randomized trial (2011-2012), we examined survey and electronic health record data to assess clinical and sociodemographic factors associated with uptake of ADA-recommended postpartum screening. Participants included 1642 women (76% racial/ethnic minorities) identified with GDM according to the Carpenter and Coustan criteria in a health system that deploys population-level strategies to promote screening. To contextualize these analyses, screening rates derived from the GEM trial were compared with those in the health system overall using registry data from a concurrent 10-year period (2007-2016, n=21 974).ResultsOverall 52% (n=857) completed recommended postpartum screening in the analytic sample, comparable to 45.7% (n=10 040) in the registry. Screening in the analytic sample was less likely among women at elevated risk for type 2 diabetes, assessed using items from an ADA risk test (vs non-elevated; adjusted rate ratio (aRR)=0.86 (95% CI 0.75 to 0.98)); perinatal depression (0.88 (0.79 to 0.98)); preterm delivery (0.84 (0.72 to 0.98)); parity ≥2 children (vs 0; 0.80 (0.69 to 0.93)); or less than college education (0.79 (0.72 to 0.86)). Screening was more likely among Chinese Americans (vs White; 1.31 (1.15 to 1.49)); women who attended a routine postpartum visit (5.28 (2.99 to 9.32)); or women who recalled receiving healthcare provider advice about screening (1.31 (1.03 to 1.67)).ConclusionsGuideline-recommended postpartum diabetes screening varied by patient clinical and sociodemographic factors. Findings have implications for developing future strategies to improve postpartum care.

Objective The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life. Study Design This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6–8) years after their index pregnancy, and trained staff measured their blood pressure (systolic blood pressure [SBP]; diastolic blood pressure [DBP]). The association between values and the shape of the glucose curve during OGTT in the index pregnancy and the primary outcome defined as elevated BP (SBP ≥120, DBP ≥80 mm Hg, or receiving anti-HTN medications), and secondary outcome defined as stage 1 or higher (SBP ≥130, DBP ≥80 mm Hg, or receiving anti-HTN medications) at follow-up were evaluated using multivariable regression, adjusting for maternal age, body mass index, and pregnancy-associated hypertension during the index pregnancy. Results There was no association between fasting, 1-hour OGTT, and the outcomes. However, the 2-hour OGTT value was positively associated (adjusted odds ratio [aRR] per 10-unit increase 1.04, 95% CI 1.01–1.08), and the 3-hour was inversely associated (aRR per 10-unit increase 0.96, 95% CI 0.93–0.99) with the primary outcome. When the shape of the OGTT curve was evaluated, a monophasic OGTT response (peak at 1 hour followed by a decline in glucose) was associated with increased risk of elevated BP (41.3vs. 23.5%, aRR 1.66, 95% CI 1.17–2.35) and stage 1 HTN or higher (28.5 vs. 14.7%, aRR 1.83, 95% CI 1.15–2.92), compared with a biphasic OGTT response. Conclusion Among persons with mild GDM or lesser degrees of glucose intolerance, the shape of the OGTT curve during pregnancy may help identify women who are at risk of HTN later in life, with biphasic shape to be associated with lower risk. Key Points The shape of the Oral Glucose Tolerance Test curve may help identify patients who are at risk of having elevated BP or HTN 5 to 10 years following pregnancy. The 2-hour Oral Glucose Tolerance Test values is positively associated with elevated BP 5 to 10 years following pregnancy. This supports the concept of pregnancy as a window to future health and represents a potential novel biomarker for maternal cardiovascular health screening. [ABSTRACT FROM AUTHOR]

Carbohydrates are a common and economical energy source in animal feeds. However, most fish show a persistent postprandial hyperglycemia after intake of a high-carbohydrate diet. Unfortunately, the mechanism of glucose metabolism in fish is still unclear. In the present study, tiger puffer (Takifugu rubripes) and turbot (Scophthalmus maximus) were intraperitoneally injected or orally administered with glucose or fructose (500 mg/kg body weight) to evaluate the ability of fish to utilize carbohydrates. Afterwards, serum glucose, fructose, pyruvate, insulin levels, and acute hypoxia tolerance were measured. Our results showed increased serum glucose level and then decreased post intraperitoneal injection with glucose, and reached a peak after 0.5 hours in turbot and 1 hour in tiger puffer. Tiger puffer had significantly lower liver glycogen, serum glucose, fructose, pyruvate, and insulin contents than turbot. Glucose and fructose only induced insulin secretion in turbot, but did not change serum insulin level in tiger puffer. Glucose was a stronger stimulator of insulin than fructose in the two marine species. Both intraperitoneal injection and oral fructose intake increased serum glucose level, while intraperitoneal or oral glucose also increased serum fructose level. Intraperitoneal injection of glucose promoted absorption and utilization of glucose in the blood more effectively than oral glucose intake. In addition, turbot and tiger puffer were intolerant to acute hypoxia, whereas supplementation with glucose or fructose improved hypoxia tolerance in the two marine fishes by activating anaerobic glycolysis. Taken together, our results provide important scientific information for understanding the mechanism for glucose and fructose utilization and improving hypoxia tolerance in fish. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluated if fetuses of subjects with one elevated value on the 3-h GTT had a measurable physiologic difference in fetal C-peptide levels as compared to those with no elevated values on the GTT. Methods: We performed a prospective cohort study to evaluate insulin levels in singleton non-anomalous fetuses of subjects with one elevated value on the GTT as compared to subjects with no elevated values on their GTT. Fetal insulin levels were measured by fetal C-peptide in cord blood. Distribution of data was assessed and outliers representing values > the 99th and < the 1st percentiles were excluded. Data were log transformed to achieve normal distribution and univariable analyses were performed to compare fetal C-peptide levels, baseline maternal characteristics and perinatal outcomes in subjects with one elevated value as compared those with no elevated values. Results: Our analysis included 99 subjects, with 49 subjects in the one elevated value group and 50 subjects in the no elevated values group. Fetal C-peptide levels (picomoles per liters, pmol/L), were significantly higher in the elevated value group as compared to the no elevated value group (mean ± SD; 4.6 ± 0.8 vs. 4.3 ± 0.7, P = 0.046, respectively). In univariable analysis, there was no significant difference in maternal characteristics or adverse composite perinatal outcomes. Conclusion: Fetuses of subjects who had one elevated value on their GTT had a measurable physiologic difference in C-peptide levels as compared to fetuses of subjects with no elevated values on the GTT. [ABSTRACT FROM AUTHOR]

ContextHispanic women are at elevated risk of gestational glucose intolerance and postpartum type 2 diabetes compared with non-Hispanic White women. Identification of potentially modifiable factors contributing to this trajectory of beta-cell dysfunction is warranted.ObjectiveWe aimed to determine the association between rate of gestational weight gain (rGWG) and glucose-insulin metabolism in Hispanic pregnant women with overweight and obesity.MethodsThis cross-sectional, observational study, conducted from 2018-2020 at the clinical research center at University of California, Irvine, included 33 nondiabetic Hispanic pregnant women at 28 to 30 weeks' gestation with pre-pregnancy body mass index (BMI) 25.0 to 34.9 kg/m2. Participants consumed a standardized liquid mixed meal after an overnight fast. Serial blood samples were collected at fasting and up to 2 hours postprandial. The glucose and insulin area under the curve (AUC), insulin sensitivity index (ISI) and insulin secretion sensitivity index (ISSI)-2 were computed.ResultsAverage rGWG (0.36 ± 0.22 kg/week) was classified as excessive in 60% of women. While rGWG was not associated with the glucose or insulin AUC or ISI, it accounted for 13.4% of the variance in ISSI-2 after controlling for covariates (maternal age, parity, and pre-pregnancy BMI); for each 1 unit increase in rGWG, ISSI-2 decreased 2.1 units (P = 0.015).ConclusionEven in the absence of gestational diabetes, rGWG was inversely associated with beta-cell function in a high-risk population of Hispanic pregnant women with overweight and obesity. Beta-cell decline is an established risk factor for transition to type 2 diabetes, and these cross-sectional findings highlight rGWG as a potentially modifiable contributor to this process.

ObjectiveThe contribution of beta-cell dysfunction to type 2 diabetes (T2D) is not restricted to insulinopenia in the late stages of the disease. Elevated fasting insulinemia in normoglycemic humans is a major factor predicting the onset of insulin resistance and T2D, demonstrating an early alteration of beta-cell function in T2D. Moreover, an early and chronic increase in fasting insulinemia contributes to insulin resistance in high-fat diet (HFD)-fed mice. However, whether there are genetic factors that promote beta-cell-initiated insulin resistance remains undefined. Human variants of the mitochondrial transporter ABCB10, which regulates redox by increasing bilirubin synthesis, have been associated with an elevated risk of T2D. The effects of T2D ABCB10 variants on ABCB10 expression and the actions of ABCB10 in beta-cells are unknown.MethodsThe expression of beta-cell ABCB10 was analyzed in published transcriptome datasets from human beta-cells carrying the T2D-risk ABCB10 variant. Insulin sensitivity, beta-cell proliferation, and secretory function were measured in beta-cell-specific ABCB10 KO mice (Ins1Cre-Abcb10flox/flox). The short-term role of beta-cell ABCB10 activity on glucose-stimulated insulin secretion (GSIS) was determined in isolated islets.ResultsCarrying the T2Drisk allele G of ABCB10 rs348330 variant was associated with increased ABCB10 expression in human beta-cells. Constitutive deletion of Abcb10 in beta-cells protected mice from hyperinsulinemia and insulin resistance by limiting HFD-induced beta-cell expansion. An early limitation in GSIS and H2O2-mediated signaling caused by elevated ABCB10 activity can initiate an over-compensatory expansion of beta-cell mass in response to HFD. Accordingly, increasing ABCB10 expression was sufficient to limit GSIS capacity. In health, ABCB10 protein was decreased during islet maturation, with maturation restricting beta-cell proliferation and elevating GSIS. Finally, ex-vivo and short-term deletion of ABCB10 in islets isolated from HFD-fed mice increased H2O2 and GSIS, which was reversed by bilirubin treatments.ConclusionsBeta-cell ABCB10 is required for HFD to induce insulin resistance in mice by amplifying beta-cell mass expansion to maladaptive levels that cause fasting hyperinsulinemia.

The aim of the work was to define the pattern of changes and pathogenetic mechanisms of glycemic curve shape during a glucose tolerance test in rats at 6, 15, and 21 weeks of environmental space restriction. Materials and methods. A total of 55 male Wistar rats aged 6–10 months were used and divided into 4 groups (1 – intact control, 10 rats; 2, 3 and 4 of 15 rats each, which were in conditions of restricted environmental space for 6, 15 and 21 weeks, respectively). Fasting plasma levels of glucose (test strips Test Strip II on a Glucocard glucometer (ARKRAY Inc., Japan)), insulin and corticosterone (by an immunoenzymatic method using commercial kits for rats from Monobind, USA) were measured, glucose tolerance tests (GTT) were performed, the HOMA index and the insulin/corticosterone ratio were calculated. Results. The 6-week environmental space restriction, immobility and complex communication relations resulted in a hypoinsulinemic-hypoglycemic type of the glycemic curve with high tissue glucose sensitivity in animals which were in the conditions described (the HOMA index was significantly decreased to 0.21 versus 0.55 in the control), the characteristic delayed hyperglycemic peak at the 30th min of the test slowly returned to the euglycemic level by only the 90th min against the 30th min in the controls. The 15-week restriction caused a hypoinsulinemic curve with preserved tissue glucose sensitivity (the HOMA index 0.33 versus 0.55 in the controls). Alterations in postprandial glucose absorption were manifested by the highest glucose concentration at the 15th min of the test, a very slow decrease in the glucose level in the post-absorption period not being restored to baseline values by the 90th min. The 21-week restriction shaped a diabetic type of the glycemic curve, impaired tissue glucose sensitivity (a substantial and significant increase in the calculated HOMA index from 0.55 in the controls to 0.95) and resulted in the development of insulin resistance. Conclusions. The environmental space restriction, immobility and complex communication relations gradually induce a range of disorders in animals and change the glycemic response shape to glucose load, impair prandial insulin secretion, augment hyperglycemic effects of counterinsular hormones (corticosterone), and realize dysfunctional manifestations of prandial/postprandial glycemia. 6 weeks of restrictions and challenges shape the hypoinsulinemic-hypoglycemic type of the glycemic curve with high tissue glucose sensitivity, while 15 weeks result in the hypoinsulinemic curve with preserved tissue glucose sensitivity. 21 weeks show the diabetic type of the glycemic curve with impaired tissue glucose sensitivity and the development of insulin resistance.

Background/Objective: Diet is a risk factor for gestational diabetes mellitus (GDM). There are few studies on women’s diet and glucose tolerance test (GTT) results during pregnancy. The objective of this study was to evaluate the relationship between one’s previous diet and the number of abnormal values on the diagnostic GTT in women with GDM. We hypothesized that there would be an inverse relation between antioxidant micronutrient consumption and the number of abnormal GTT values. Methods: This cross-sectional study included 60 women diagnosed with GDM (2-h, 75 g-GTT), divided in two groups as follows: 1 abnormal glucose value and 2–3 abnormal values. Shortly after the diagnosis, participants answered a validated food frequency questionnaire to assess their food consumption in the last 6 months. The Mann–Whitney test was used to compare the dietary intake of the participants in the two groups. Results: The participant characteristics were similar. The median intake of total calories, carbohydrates, lipids, and proteins did not differ significantly between groups. Participants with 1 abnormal GTT value had significantly higher intakes of fiber (11.9 vs. 11.0 g/day p = 0.049), vitamin D (40.6 vs. 40.4 mcg/day p = 0.049), and vitamin C (180.0 vs. 151.0 mg/day p = 0.008) than those with 2–3 abnormal values. Conclusions: Our results suggest a possible association between the consumption of fiber and antioxidant micronutrients and the number of abnormal GTT values.

Objective: This study was performed to determine the effect of fasting on reproducibility of the glucose tolerance test. Due to individual variation in animal feeding behaviors, fasting animals prior to metabolic and behavioral experiments is widely held to reduce inter-subject variation in glucose and metabolic parameters of preclinical rodent models. Reducing variability is especially important for studies where initial metabolite levels can influence the magnitude of experimental interventions, but fasting also imposes stress that may distort the variables of interest. One such intervention is the glucose tolerance test (GTT) which measures the maximum response and recovery following a bolus of exogenous glucose. We sought to investigate how fasting affects the response of individual mice to a GTT. Methods: Using simultaneous continuous glucose monitoring (CGM) and indirect calorimetry, we quantified blood glucose, physical activity, body temperature, metabolic rates, and food consumption levels on a minute-to-minute basis in adult male mice for 4 weeks. We tested the effects of a 4-h or 18-h fast on the GTT to examine the effect of food withdrawal in light or dark photoperiods. Studies were also performed with 4-h fasting in additional mice without implanted CGM probes. Results: Contrary to our expectations, a 4-h fast during the light photoperiod promotes a paradoxical increase in inter-animal variation in metabolic rate, physical activity, body temperature, glycemia, and glucose tolerance. This hyperglycemic and hyper-metabolic phenotype promotes increased corticosterone levels and is consistent with a behavioral stress response to food deprivation, even in well-fed mice. We find that mice undergoing an 18-h fast entered torpor, a hibernation-like state. In addition to low body temperature and metabolic rate, torpor is also associated with glucose levels 56 mg/dl lower than those seen in mice with ad libitum access to food. Moreover, the time spent in torpor affects the response to a GTT. Conclusion: Our results suggest fasting mice before glucose tolerance testing, and perhaps other experiments, can have the opposite of the intended effect where fasting can increase, rather than decrease, experimental variability.

Background: Diabetes mellitus is a common and crucial metabolic complication in kidney transplantation. It is necessary to analyze the course of glucose metabolism in patients who already have diabetes after receiving a transplant. In this study, we investigated the changes in glucose metabolism after transplantation, and a detailed analysis was performed on some patients whose glycemic status improved. Methods: The multicenter prospective cohort study was conducted between 1 April 2016 and 31 September 2018. Adult patients (aged 20 to 65 years) who received kidney allografts from living or deceased donors were included. Seventy-four subjects with pre-transplant diabetes were followed up for 1 year after kidney transplantation. Diabetes remission was defined as the results of the oral glucose tolerance test performed one year after transplantation and the presence or absence of diabetes medications. After 1-year post-transplant, 74 recipients were divided into the persistent diabetes group (n = 58) and the remission group (n = 16). Multivariable logistic regression was performed to identify clinical factors associated with diabetes remission. Results: Of 74 recipients, 16 (21.6%) showed diabetes remission after 1-year post-transplant. The homeostatic model assessment for insulin resistance numerically increased in both groups throughout the first year after transplantation and significantly increased in the persistent diabetes group. The insulinogenic index (IGI30) value significantly increased only in the remission group, and the IGI30 value remained low in the persistent diabetes group. In univariate analysis, younger age, newly diagnosed diabetes before transplantation, low baseline hemoglobin A1c, and high baseline IGI30 were significantly associated with remission of diabetes. After multivariate analysis, only newly diagnosed diabetes before transplantation and IGI30 at baseline were associated with remission of diabetes (34.00 [1.192-969.84], P = 0.039, and 17.625 [1.412-220.001], P = 0.026, respectively). Conclusion: In conclusion, some kidney recipients with pre-transplant diabetes have diabetes remission 1 year after transplantation. Our prospective study revealed that preserved insulin secretory function and newly diagnosed diabetes at the time of kidney transplantation were favorable factors for which glucose metabolism did not worsen or improve 1 year after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background and Objectives There exists a limited body of research investigating the correlation between gestational diabetes mellitus (GDM) with fetal epicardial fat thickness (FEFT). The primary objective of this study was to assess the potential of FEFT as an indicator for screening GDM in pregnant women. The study was designed as a cross-sectional analytical investigation. Materials & methods The study incorporated pregnant women who were scheduled to undergo a 75g oral glucose tolerance test (OGTT). Antenatal ultrasonography (USG) were conducted in all patients. Among the total of 200 patients, a subset of 70 patients was selected for further analysis. This subset included 35 patients with elevated results in the 75g OGTT (indicating cases of GDM) and 35 patients with normal results. Results: There was a significant increase in FEFT among pregnant women with GDM. Furthermore, the elevated FEFT demonstrated a positive correlation with 2-hour OGTT serum glucose values. The mean FEFT in mothers with GDM was found to be significantly larger compared to mothers without GDM. To assess the predictive capability of FEFT for GDM, an ROC curve was constructed which demonstrated a high sensitivity of 95.57% and specificity of 91% for FEFT as a predictor of GDM. Conclusion: Assessing the FEFT in fetuses could serve as a novel marker for diagnosing GDM. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a condition characterized by hyperglycemia that is first diagnosed during pregnancy. It increases both fetal and maternal risk and is related to future metabolic abnormalities in women and their offspring. Therefore, appropriate diagnosis and management of GDM are crucial. Current Concepts: There are two strategies to diagnose GDM--a one-step strategy comprising a 75 g oral glucose tolerance test (OGTT), and a two-step strategy involving a 50 g OGTT followed by a 100 g OGTT. The former can detect more glucose abnormality during pregnancy; however, either method is acceptable, considering the evidence regarding pregnancy outcomes. The mainstay of glucose management in GDM is medical nutrition therapy with appropriate physical activity and self-monitoring of glucose. Insulin therapy is required if hyperglycemia cannot be controlled by lifestyle interventions. Generally, insulin therapy is immediately discontinued after childbirth, and 75 g OGTT is recommended at 4 to 12 weeks in the postpartum period and every 1 to 3 years thereafter. Lifestyle intervention is important in women with a history of GDM to prevent future diabetes. Discussion and Conclusion: GDM prevalence is increasing because of higher maternal age and prevalent obesity. Healthcare providers and women of childbearing age need to be more careful with regard to the detection and management of GDM, and treatment strategies should be personalized. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Older age is associated with greater prevalence of hyperinsulinemia, type 2 diabetes, and fatty liver disease. These metabolic conditions and aging are bidirectionally linked to mitochondrial dysfunction and telomere attrition. Although effectively addressing these conditions is important for influencing the health and the lifespan, it is particularly challenging in older age. We reported that E4orf1, a protein derived from human adenovirus Ad36, reduces hyperinsulinemia, improves glucose clearance, and protects against hepatic steatosis in younger mice exposed to high fat diet (HFD). Here, we tested if E4orf1 will improve glycemic control, liver fat accumulation, mitochondrial integrity, and reduce telomere attrition in older mice. RESEARCH DESIGN AND METHODS: We used 9-month-old mice that inducibly expressed E4orf1 in adipose tissue and non-E4orf1 expressing control mice. Mice were maintained on a 60% (kcal) HFD for 20 weeks and glycemic control was determined by intraperitoneal glucose tolerance test at week 20. Following 20 weeks of HF-feeding, mice were sacrificed and liver tissues collected to determine the expression of aging genes using qRT-PCR based RT2 Profiler PCR array. RESULTS: Compared with the control mice, E4orf1 significantly improved glycemic control and reduced hepatic steatosis and fibrosis. Additionally, E4orf1 maintained markers of mitochondrial integrity and telomere attrition. CONCLUSION: E4orf1 has the potential to improve glycemic control in older mice, and the improvement persists even after longer term exposure. E4orf1 expression also maintains mitochondrial integrity and telomere attrition, thus delaying age-associated diseases. This provides strong evidence for therapeutic utility of E4orf1 in improving age-associated metabolic and cellular changes that occur with aging in humans.

Proliferation of pancreatic β-cells has long been known to reach its peak in the neonatal stages and decline during adulthood. However, β-cell proliferation has been studied under the assumption that all β-cells constitute a single, homogenous population. It is unknown whether a subpopulation of β-cells retains the capacity to proliferate at a higher rate and thus contributes disproportionately to the maintenance of mature β-cell mass in adults. We therefore assessed the proliferative capacity and turnover potential of virgin β-cells, a novel population of immature β-cells found at the islet periphery. We demonstrate that virgin β-cells can proliferate but do so at rates similar to those of mature β-cells from the same islet under normal and challenged conditions. Virgin β-cell proliferation rates also conform to the age-dependent decline previously reported for β-cells at large. We further show that virgin β-cells represent a long-lived, stable subpopulation of β-cells with low turnover into mature β-cells under healthy conditions. Our observations indicate that virgin β-cells at the islet periphery can divide but do not contribute disproportionately to the maintenance of adult β-cell mass.

ObjectiveMaintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (α, β, and δ cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in somatostatin-secreting δ cells, we hypothesized that GPR120 activation stimulates insulin and glucagon secretion via inhibition of somatostatin release.MethodsGlucose tolerance tests were performed in mice after administration of selective GPR120 agonist Compound A. Insulin, glucagon, and somatostatin secretion were measured in static incubations of isolated mouse islets in response to endogenous (ω-3 polyunsaturated fatty acids) and/or pharmacological (Compound A and AZ-13581837) GPR120 agonists. The effect of Compound A on hormone secretion was tested further in islets isolated from mice with global or somatostatin cell-specific knock-out of gpr120. Gpr120 expression was assessed in pancreatic sections by RNA in situ hybridization. Cyclic AMP (cAMP) and calcium dynamics in response to pharmacological GPR120 agonists were measured specifically in α, β, and δ cells in intact islets using cAMPER and GCaMP6 reporter mice, respectively.ResultsAcute exposure to Compound A increased glucose tolerance, circulating insulin, and glucagon levels in vivo. Endogenous and/or pharmacological GPR120 agonists reduced somatostatin secretion in isolated islets and concomitantly demonstrated dose-dependent potentiation of glucose-stimulated insulin secretion and arginine-stimulated glucagon secretion. Gpr120 was enriched in δ cells. Pharmacological GPR120 agonists reduced cAMP and calcium levels in δ cells but increased these signals in α and β cells. Compound A-mediated inhibition of somatostatin secretion was insensitive to pertussis toxin. The effect of Compound A on hormone secretion was completely absent in islets from mice with either global or somatostatin cell-specific deletion of gpr120 and partially reduced upon blockade of somatostatin receptor signaling by cyclosomatostatin.ConclusionsInhibitory GPR120 signaling in δ cells contributes to both insulin and glucagon secretion in part by mitigating somatostatin release.

Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.

AimTo investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D).Materials and methodsThe Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline.ResultsAfter screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance.ConclusionsThe longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D.

The proportion of adipose depots varies considerably between fattailed (FT) and thin-tailed (TT) sheep breeds. FT breeds accumulate majority of body fat in fat-tail depot, whereas TT breeds deposit considerable proportion of body fat in visceral depots. These differences in proportion of adipose depots seem to affect body metabolism due to differences in metabolism of different depots. Hence, the current research aimed to evaluate the response of fat-tailed lambs (FTL) and thin-tailed lambs (TTL) to glucose and insulin challenges during negative energy balance (NEB) and positive energy balance (PEB). Glucose tolerance and insulin challenge tests were conducted on randomly selected lambs from each genotypes at the end of induced NEB and PEB. Glucose injection during NEB caused greater plasma glucose concentration in TTL, whereas in PEB, the enhancement in glucose concentration as a consequence of glucose injection was higher in FTL (P=0.09). The area under the glucose curve was higher in FT compared to TT lambs during glucose tolerance test regardless of energy balance (EB; P=0.03). The clearance rates of insulin (P=0.09) and glucose (P=0.006) in the respective insulin and glucose tolerance tests were higher during PEB compared to NEB regardless of the genotypes. These results demonstrated that induced NEB can enhance insulin resistance in both FT and TT lambs, severity of which is greater in FT than in TT lambs. [ABSTRACT FROM AUTHOR]

The aim of the work was to define the pattern of changes and pathogenetic mechanisms of glycemic curve shape during a glucose tolerance test in rats at 6, 15, and 21 weeks of environmental space restriction. Materials and methods. A total of 55 male Wistar rats aged 6-10 months were used and divided into 4 groups (1 - intact control, 10 rats; 2, 3 and 4 of 15 rats each, which were in conditions of restricted environmental space for 6, 15 and 21 weeks, respectively). Fasting plasma levels of glucose (test strips Test Strip II on a Glucocard glucometer (ARKRAY Inc., Japan)), insulin and corticosterone (by an immunoenzymatic method using commercial kits for rats from Monobind, USA) were measured, glucose tolerance tests (GTT) were performed, the HOMA index and the insulin/corticosterone ratio were calculated. Results. The 6-week environmental space restriction, immobility and complex communication relations resulted in a hypoinsulinemic-hypoglycemic type of the glycemic curve with high tissue glucose sensitivity in animals which were in the conditions described (the HOMA index was significantly decreased to 0.21 versus 0.55 in the control), the characteristic delayed hyperglycemic peak at the 30th min of the test slowly returned to the euglycemic level by only the 90th min against the 30th min in the controls. The 15-week restriction caused a hypoinsulinemic curve with preserved tissue glucose sensitivity (the HOMA index 0.33 versus 0.55 in the controls). Alterations in postprandial glucose absorption were manifested by the highest glucose concentration at the 15th min of the test, a very slow decrease in the glucose level in the post-absorption period not being restored to baseline values by the 90th min. The 21-week restriction shaped a diabetic type of the glycemic curve, impaired tissue glucose sensitivity (a substantial and significant increase in the calculated HOMA index from 0.55 in the controls to 0.95) and resulted in the development of insulin resistance. Conclusions. The environmental space restriction, immobility and complex communication relations gradually induce a range of disorders in animals and change the glycemic response shape to glucose load, impair prandial insulin secretion, augment hyperglycemic effects of counterinsular hormones (corticosterone), and realize dysfunctional manifestations of prandial/postprandial glycemia. 6 weeks of restrictions and challenges shape the hypoinsulinemic-hypoglycemic type of the glycemic curve with high tissue glucose sensitivity, while 15 weeks result in the hypoinsulinemic curve with preserved tissue glucose sensitivity. 21 weeks show the diabetic type of the glycemic curve with impaired tissue glucose sensitivity and the development of insulin resistance. [ABSTRACT FROM AUTHOR]

As many as 1 in 3 patients with gestational diabetes mellitus have impaired glucose metabolism when screened postpartum. These patients have a 40% to 70% lifetime risk of progression to type 2 diabetes mellitus, but progression can be delayed or prevented by lifestyle interventions or medication. The American College of Obstetricians and Gynecologists and the American Diabetes Association recommend a glucose tolerance test at 4 to 12 weeks postpartum for all patients with gestational diabetes mellitus. Despite these recommendations, postpartum screening rates are typically <50%, representing a major healthcare "quality gap." The Society for Maternal-Fetal Medicine proposes a uniform metric that identifies the percentage of persons with gestational diabetes mellitus who completed a 75-g, 2-hour glucose tolerance test within 12 weeks after delivery. The metric is designed to be measured using diagnosis and procedure codes in payor claims data. Barriers to screening are discussed. Possible uses of the metric for quality improvement projects are outlined. Increasing the rate of postpartum diabetes screening should facilitate timely referral to implement lifestyle modifications, medication, and long-term follow-up. Use of the metric in financial incentive programs is discouraged at this time. [ABSTRACT FROM AUTHOR]

Adipose tissue eosinophils (ATEs) are important in the control of obesity-associated inflammation and metabolic disease. However, the way in which ageing impacts the regulatory role of ATEs remains unknown. Here, we show that ATEs undergo major age-related changes in distribution and function associated with impaired adipose tissue homeostasis and systemic low-grade inflammation in both humans and mice. We find that exposure to a young systemic environment partially restores ATE distribution in aged parabionts and reduces adipose tissue inflammation. Approaches to restore ATE distribution using adoptive transfer of eosinophils from young mice into aged recipients proved sufficient to dampen age-related local and systemic low-grade inflammation. Importantly, restoration of a youthful systemic milieu by means of eosinophil transfers resulted in systemic rejuvenation of the aged host, manifesting in improved physical and immune fitness that was partially mediated by eosinophil-derived IL-4. Together, these findings support a critical function of adipose tissue as a source of pro-ageing factors and uncover a new role of eosinophils in promoting healthy ageing by sustaining adipose tissue homeostasis.

The bile acid receptor, TGR5, is a key regulator of glucose homeostasis, but the mechanisms by which TGR5 signaling improves glucose regulation are incompletely defined. In particular, TGR5 has an increasingly appreciated role in liver physiology and pathobiology; however, whether TGR5 signaling within the liver contributes to its glucoregulatory effects is unknown. Therefore, we investigated the role of hepatocyte TGR5 signaling on glucose regulation using a hepatocyte-specific TGR5 knockout mouse model. Hepatocyte-specific Tgr5Hep+/+ and Tgr5Hep-/- mice were fed a high fat diet (HFD) for 7 weeks and then orally gavaged with three doses of a highly potent, TGR5-specific agonist, Compound 18 (10 mg/kg), or vehicle, over 72 h and underwent an oral glucose tolerance test (OGTT) after the last dose. Herein, we report that TGR5 mRNA and protein is present in mouse hepatocytes. Cumulative food intake, body weight, and adiposity do not differ between Tgr5Hep+/+ and Tgr5Hep-/- mice with or without treatment with Compound 18. However, administration of Compound 18 improves glucose tolerance in Tgr5HEP+/+ mice, but not in Tgr5Hep-/- mice. Further, this effect occurred independent of body weight and GLP-1 secretion. Together, these data demonstrate that TGR5 is expressed in hepatocytes, where it functions as a key regulator of whole-body glucose homeostasis.

Moringa seeds have been used traditionally in the management of type 2 diabetes mellitus (T2DM) and contain potent bioactive isothiocyanates. This study evaluated the efficacy of an isothiocyanate-rich moringa seed extract in delaying the onset of T2DM in UC Davis T2DM rats, a well validated model which closely mimics T2DM in humans. Rats were separated into three groups; control, moringa seed extract at 0.4%, and a weight matched group. Rats were fed respective diets for 8 months, during which energy intake, body weight, the onset of diabetes circulating hormones, metabolites and markers of inflammation and liver function, and were monitored. The MS group had a significantly slower rate of diabetes onset p = 0.027), lower plasma glucose (p = 0.043), and lower HbA1c (p = 0.008) compared with CON animals. There were no significant differences in food intake and body weight between all groups. This study demonstrated MS can delay the onset of diabetes in the UC Davis T2DM rat model to a greater extent than moderate caloric restriction (by comparison to the WM group). The results support its documented traditional uses and a bioactive role of moringa isothiocyanates and suggest the potential efficacy for moringa supplementation for diabetes management in populations at risk for T2DM.

ObjectivesThis study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the associations of bile acids with GDM risk or had interactive effects with bile acids on GDM risk.DesignWe conducted a 1:1 nested case-control study (n = 486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational week). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk.ResultsOf the 6 detectable LPCs, LPC14:0 less than 0.24 nmol/mL, LPC15:0 at 0.45 nmol/mL or greater, and LPC18:0 at 18.00 nmol/mL or greater were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤ 0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤ 0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, the presence of DCA at 0.36 nmol/mL or less greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 8.18 (2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, the presence of GUDCA at 0.07 nmol/mL or less also greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 17.2 (1.77-168) up to 73.8 (12.7-429), with significant additive interaction.ConclusionsLPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM, and its molecular mechanism is worth further investigations.

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ∼26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 × 10-8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1 Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

α-Linolenic acid (ALA) is an essential fatty acid and the precursor for long-chain n-3 PUFA. However, biosynthesis of n-3 PUFA is limited in a Western diet likely due to an overabundance of n-6 PUFA. We hypothesized that dietary reduction of n-6/n-3 PUFA ratio is sufficient to promote the biosynthesis of long-chain n-3 PUFA, leading to an attenuation of high fat (HF) diet-induced obesity and inflammation. C57BL/6 J mice were fed a HF diet from ALA-enriched butter (n3Bu, n-6/n-3=1) in comparison with isocaloric HF diets from either conventional butter lacking both ALA and LA (Bu, n-6/n-3=6), or margarine containing a similar amount of ALA and abundant LA (Ma, n-6/n-3=6). Targeted lipidomic analyses revealed that n3Bu feeding promoted the bioconversion of long-chain n-3 PUFA and their oxygenated metabolites (oxylipins) derived from ALA and EPA. The n3Bu supplementation attenuated hepatic TG accumulation and adipose tissue inflammation, resulting in improved insulin sensitivity. Decreased inflammation by n3Bu feeding was attributed to the suppression of NF-κB activation and M1 macrophage polarization. Collectively, our work suggests that dietary reduction of the n-6/n-3 PUFA ratio, as well as total n-3 PUFA consumed, is a crucial determinant that facilitates n-3 PUFA biosynthesis and subsequent lipidomic modifications, thereby conferring metabolic benefits against obesity-induced inflammation and insulin resistance.

Insulin resistance is a major factor in obesity-linked type 2 diabetes. PPARγ is a master regulator of adipogenesis, and small molecule agonists, termed thiazolidinediones, are potent therapeutic insulin sensitizers. Here, we studied the role of transcriptional co-activator with PDZ-binding motif (TAZ) as a transcriptional co-repressor of PPARγ. We found that adipocyte-specific TAZ knockout (TAZ AKO) mice demonstrate a constitutively active PPARγ state. Obese TAZ AKO mice show improved glucose tolerance and insulin sensitivity compared to littermate controls. PPARγ response genes are upregulated in adipose tissue from TAZ AKO mice and adipose tissue inflammation was also decreased. In vitro and in vivo mechanistic studies revealed that the TAZ-PPARγ interaction is partially dependent on ERK-mediated Ser112 PPARγ phosphorylation. As adipocyte PPARγ Ser112 phosphorylation is increased in obesity, repression of PPARγ activity by TAZ could contribute to insulin resistance. These results identify TAZ as a new factor in the development of obesity-induced insulin resistance.

Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving glycemic control in obesity-associated diabetic subjects. However, an acute and severe intervention without proper maintenance could reverse the initial benefits, with additional metabolic derangements. To assess the effects of an acute caloric restriction in a metabolic syndrome model, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without a 10-day body mass (BM) recovery period, along with their respective ad libitum controls. An oral glucose tolerance test (oGTT) was performed after CR and BM recovery. Both strains had higher rates of mass gain during recovery vs. ad lib controls; however, the regain was partial (ca. 50% of ad lib controls) over the measurement period. Retroperitoneal and epididymal adipose masses decreased 30% (8.8 g, P < 0.001) in OLETF; however, this loss only accounted for 11.5% of the total BM loss. CR decreased blood glucose AUC 16% in LETO and 19% in OLETF, without significant decreases in insulin. Following CR, hepatic expression of the gluconeogenic enzyme, PEPCK, was reduced 55% in OLETF compared to LETO, and plasma triglycerides (TG) decreased 86%. Acute CR induced improvements in glucose tolerance and TG suggestive of improvements in metabolism; however, partial recovery of BM following CR abolished the improvement in glucose tolerance. The present study highlights the importance of proper maintenance of BM after CR as only partial recovery of the lost BM reversed benefits of the initial mass loss.

Insulin administration for the management of diabetes is accompanied by hypoglycemia, which is expected to be mitigated by glucose-responsive smart insulin that has self-regulation ability in response to blood glucose level (BGL) fluctuation. Here, we have prepared a new insulin analog by modifying insulin with forskolin (designated as insulin-F), a glucose-transporter (Glut) inhibitor. In vitro, insulin-F is capable of binding to Glut on erythrocyte ghosts, which can be inhibited by glucose and cytochalasin B. Upon subcutaneous injection in type 1 diabetic mice, insulin-F maintains BGLs below 200 mg mL-1 for up to 10 h, and achieves 20 h with two sequential injections. Moreover, insulin-F also binds to endogenous Gluts. Upon a glucose challenge, the elevated level of glucose competitively replaces and liberates insulin-F that binds to Glut, rapidly restoring BGLs to the normal range.