Oral Glucose Tolerance Test Curve Research Articles

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus.

Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = -3.71, p < 0.001). Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment.

Saroglitazar mitigated NASH-associated hepatic injury in dexamethasone-treated rats via modulating autophagy, apoptosis, and necroptosis

This study aimed to evaluate the possible ameliorative effects of saroglitazar (SAR) on aspects of hepatic injury in dexamethasone (DEX)-induced nonalcoholic steatohepatitis (NASH) in rats.Wistar rats received SAR (2 or 4 mg/kg/day, orally) or metformin (MET, 500 mg/kg/day, orally) for one week before and concurrently with DEX administration (8 mg/kg/day, i.p., for 6 days. Control and drug control groups received vehicle or the higher dose of SAR, respectively. At the end of the experiment, an oral glucose tolerance test (OGTT) was conducted, serum hepatic function parameters and lipid profile were assessed, and hepatic histological changes were evaluated. Moreover, hepatic p-Akt/Akt ratios, malondialdehyde (MDA) content, SREBP-1, FOXO1, LC3, cleaved caspase-3, and p-MLKL protein levels were determined. Furthermore, hepatic immunohistochemical expressions of FOXO1, caspase-3, Bcl-2, LC3, and P62 were examined.SAR (mainly at 4 mg/kg/day) significantly improved Area under the OGTT curve (P < 0.0001), hepatic function parameters, lipid profile, and hepatic histopathological features in DEX-administered rats. Moreover, SAR significantly attenuated DEX-induced increases in hepatic MDA content (P < 0.05), SREBP-1 levels (P < 0.0001), and nuclear FOXO1, caspase-3, LC3, P62, and p-MLKL protein expressions (P < 0.0001). Furthermore, SAR significantly enhanced hepatic p-Akt/Akt ratio and Bcl-2 protein expression in DEX-administered rats (P < 0.0001). The higher dose of SAR showed greater hepatoprotective effects compared to its corresponding lower dose and MET in most assessments, approaching levels similar to the control group.SAR mitigated hepatic injury associated with DEX-induced NASH in rats, suggesting it might be a potential hepatoprotective drug for patients with or at high risk of NASH.

Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.

Fibroblast growth factor (FGF) 15/19, which is expressed in and secreted from the distal ileum, can regulate hepatic glucose metabolism in an endocrine manner. The levels of both bile acids (BAs) and FGF15/19 are elevated after bariatric surgery. However, it is unclear whether the increase in FGF15/19 is induced by BAs. Moreover, it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery. To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy (SG). By calculating and comparing the changes of body weight after SG with SHAM group, we examined the weight-loss effect of SG. The oral glucose tolerance test (OGTT) test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG. By detecting the glycogen content, expression and activity of glycogen synthase as well as the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (Pepck), we evaluated the hepatic glycogen content and gluconeogenesis activity. We examined the levels of total BA (TBA) together with the farnesoid X receptor (FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery. Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4 (FGFR4) with its corresponding signal pathways involved in glucose metabolism were detected. After surgery, food intake and body weight gain of SG group was decreased compare with the SHAM group. The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG, while the expression of the key enzyme for hepatic gluconeogenesis: G6Pase and Pepck, were depressed. TBA levels in serum and portal vein were both elevated after SG, the FXR-agonistic BA subspecies: Chenodeoxycholic acid (CDCA), lithocholic acid (LCA) in serum and CDCA, DCA, LCA in portal vein were all higher in SG group than that in SHAM group. Consequently, the ileal expression of FXR and FGF15 were also advanced in SG group. Moreover, the hepatic expression of FGFR4 was stimulated in SG-operated rats. As a result, the activity of its corresponding pathway for glycogen synthesis: FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated, while the corresponding pathway for hepatic gluconeogenesis: FGFR4- cAMP regulatory element-binding protein- peroxisome proliferator-activated receptor γ coactivator-1α pathway was suppressed. Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR. Furthermore, the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Flat maternal glucose response curve and adverse pregnancy outcome.

The significance of a flat oral glucose tolerance test (OGTT) response curve in pregnancy remains unclear. We investigated the association of a flat curve with pregnancy outcomes. Retrospective cohort study. Flat OGTT curve was defined by an area under the curve below the 10th percentile. Pregnancy outcomes were compared between flat and normal curve. Of the 2673 eligible women, 269 had a flat response curve. Compared with the normal-response group, the flat-curve group had a lower mean birthweight (3363 ± 547 g vs. 3459 ± 519 g, p < 0.005), higher probability of small for gestational age (SGA) (19% vs. 12%, p < 0.005, aOR = 1.75, 95% CI 1.24-2.47), and 5-min Apgar score < 7 (1.12% vs. 0.29%, p < 0.05, aOR = 3.95, 95% CI 1.01-15.5). There were no differences in obstetric or maternal outcomes. Flat OGTT is associated with lower birthweight, higher rates of SGA, and low Apgar scores. Detecting this previously unrecognized risk group, could potentially reduce these complications.

Effects of herbal tea (Platostoma palustre) on blood glucose regulation in vivo

Platostoma palustre jelly is a traditional food. Platostoma palustre has been used as folk medicine and is effective against heat-shock, hypertension and diabetes. Therefore, the aim of in vivo study was to determine the effects of herbal tea (Platostoma palustre) on blood glucose regulation. The commercial herbal tea (Platostoma palustre) was kindly provided by Yueta Agricultural Biotechnology Inc. Adult male 18 Institute of Cancer Research (ICR) mice [8 weeks old; body weight (BW) between 31-33 g] with specific pathogen-free conditions were used for this study. All ICR mice were divided respectively the normal control group (n = 6), the negative control group (n = 6), and the herbal tea group (n = 6). The ICR mice (the negative control group and the herbal tea group) were intraperitoneally injected with streptozotocin (65 mg/kg BW) and nicotinamide (230 mg/kg BW) for inducing the symptoms of hyperglycemia. In the herbal tea group, the herbal tea (10 mL/kg BW) was administrated to ICR mice by gavage. To monitor the blood glucose levels in ICR mice, blood was obtained from the tail of ICR mice, and blood glucose levels were determined using the external glucometer. Blood glucose measurements were conducted once in ICR mice before the experiment and were detected once per month after the experiment. Additionally, the change of ICR mice’ BW, the blood glucose of ICR mice, and the observation of ICR mice’ behavior were monitored and detected during the experiment. The results of this experiment showed · Weight change: the weight gain of the negative control group and the herbal tea group were significantly lower than those of the normal control group and there was no significant difference between the negative control group and the herbal tea group. · Fasting blood glucose and postprandial blood glucose: the fasting blood glucose of the negative control group was significantly higher than that of the normal control group, while the herbal tea group had a tendency to lower the fasting blood glucose, but there was no significant difference compared with the negative control group. The postprandial blood glucose level results showed that the negative control group was significantly higher than the normal control group. The postprandial blood glucose level of the herbal tea group was between the normal control group and the negative control group at the 4th week administration with the herbal tea. At the 8th week administration with the herbal tea, there was a significant difference compared with the negative control group. · Oral glucose tolerance test (OGTT): 4 to 12 weeks after hyperglycemia was induced, the blood glucose levels of the negative control group at each OGTT test point were significantly higher than those of the normal control group. The blood glucose level at the test point tended to decrease, but there was no significant difference from the negative control group. By calculating the area under the OGTT curve, it was found that the area under the curve of the negative control group was significantly higher than that of the normal control group, while the results of the herbal tea group at the 8th and 12th weeks were significantly lower than those of the negative control group. Taken all results together, the hyperglycemia was successfully induced in the experimental ICR mice. After administrating with the herbal tea, the fasting blood glucose level of the ICR mice tended to improve. In addition, a significant improvement was seen in the results of postprandial blood sugar and oral glucose tolerance test effectiveness. Therefore, based on the results of this experiment, it is speculated that drinking the herbal tea for 3 months has considerable potential for blood glucose regulation, which can be used as the basis for the development of related products of the herbal tea in the future.

Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of Plantago australis.

Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAEPa) of P. australis was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAEPa significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAEPa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD50 of HAEPa was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAEPa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.

Effects of Early Risperidone Treatment on Metabolic Parameters in Socially Isolated Rats-Implication of Antipsychotic Intervention across Developmental Stages of Schizophrenia.

Second-generation antipsychotics (SGAs) is thought responsible for the metabolic abnormalities of schizophrenic patients, however, some untreated schizophrenic patients had already developed problems with glucose metabolism. The present study examined the hypothesis that schizophrenia itself but not risperidone, an extensively employed SGA, is accountable for metabolic abnormalities. A 56-day risperidone regimen (1 mg/kg/day) was employed for rats of social isolation rearing (SIR) beginning at different developmental stage (28 or 56 days after weaning, i.e., adolescent and young adulthood, respectively). Metabolic parameters including body weight, systolic blood pressure (SBP), triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and plasma glucose were measured at baseline, 28, and 56 days of the regimen. Oral glucose tolerance test (OGTT) was performed at the end of the regimen. Insulin function was evaluated by area under the curve (AUC) of OGTT, homeostasis model assessment-insulin resistance (HOMA-ir), and Matsuda index. Our results demonstrated that: (i) SIR rats presented higher body weight, plasma triglyceride, and HOMA-ir than social controls. (ii) Higher insulin resistance was specifically presented in young adult rather than adolescent SIR rats. (iii) Adolescent drugged rats showed a lower level of LDL in day 28 of the regimen than young adult. Risperidone led to a lower LDL level in only young adult IR rats in day 56 than undrugged rats. (iv) SIR-induced dysregulation of insulin can be reversed by chronic risperidone treatment beginning at adolescence but not young adulthood. Our findings support the primary role of schizophrenia in metabolic abnormalities and risperidone appear beneficial when administered earlier.

Influence of concurrent administration of the methanol leaf extract of Leptadenia hastata (Pers) decne (Apocynaceae) with metformin on blood glucose in diabetic rats

Objectives: Leptadenia hastata (Pers) Decne (Apocynaceae) is a common medicinal plant used in northern Nigeria either singly or together with conventional drugs to treat diabetes. This study investigated the influence of concurrent administration of the methanol leaf extract of L. hastata with metformin in streptozotocin/ nicotinamide-induced diabetic rats. Materials and Methods: Possible synergistic activity between the extract and metformin was assessed using 3 models of synergy analysis (Loewe additivity, Bliss independent and highest single agent [HSA] models). Eleven groups of Wistar rats (eight animals per group) consisting of ten groups of diabetic rats and one normal control group were used in this study. Six groups were administered with either the extract or metformin at three different doses each (50, 150 and 500 mg/kg for the extract and 30, 100 and 300 mg/kg for metformin), while another three groups were co-administered with the extract and metformin at three different ratios each (50 mg/kg: 30 mg/ kg, 150 mg/kg: 100 mg/kg and 500 mg/kg: 300 mg/kg). An oral glucose tolerance test (OGTT) was conducted at baseline and on day 14. Result: The results revealed that the extract-metformin combination brought about a synergistic reduction in the total area under the OGTT curve (based on Loewe and HSA models) as well as a synergistic reduction in blood glucose (based on Loewe, Bliss and HSA models). Conclusion: The methanol leaf extract of L. hastata produced a synergistic antidiabetic activity in streptozotocin/ nicotinamide-induced diabetic rats when combined with metformin.

Systemic glucose levels are modulated by specific wavelengths in the solar light spectrum that shift mitochondrial metabolism.

Systemic glucose levels can be modulated with specific solar wavelengths that influence mitochondrial metabolism. Mitochondrial respiration can be modulated using light that shifts ATP production with exceptional conservation of effect across species, from insects to humans. Known wavelengths have opposing effects of photobiomodulation, with longer wavelengths (660-900 nm red/infrared) increasing ATP production, and 420 nm (blue) light suppressing metabolism. Increasing mitochondrial respiration should result in a greater demand for glucose, and a decrease should result in a reduced demand for glucose. Here we have tested the hypothesis that these wavelengths alter circulating glucose concentration. We first established an oral glucose tolerance test curve in a bumblebee model, which showed sustained increase in systemic glucose beyond that seen in mammals, with a gradual normalisation over eight hours. This extended period of increased systemic glucose provided a stable model for glucose manipulation. Bees were starved overnight and given a glucose load in the morning. In the first group glucose levels were examined at hourly intervals. In the second group, bees were additionally exposed to either 670 nm or 420 nm light and their blood glucose examined. Increasing mitochondrial activity with 670 nm light at the peak of circulating glucose, resulted in a significant 50% reduction in concentration measured. Exposure to 420nm light that retards mitochondrial respiration elevated systemic glucose levels by over 50%. The impact of 670 nm and 420 nm on mitochondria is highly conserved. Hence, different wavelengths of visible light may be used to modulate systemic metabolism bidirectionally and may prove an effective agent in mammals.

LBSUN161 Relationship Of Shape Of Glucose OGTT Curves With Measures Of Cardiometabolic Health In African American Adolescents

Abstract Background and Aims Studies in youth and adults have shown that the shape of oral glucose tolerance test (OGTT) response curve may be a biomarker for insulin secretion and insulin sensitivity (IS). Individuals with monophasic (MPh) glucose response curve have lower IS and decreased beta-cell function compared to those with biphasic (BPh) pattern. The aim of this study was to assess if the shape of the glucose response curve of OGTT is associated with 2-D ECHO based indices of heart structure and function. Methods In a cross-sectional study, African American (AA) adolescents with and without obesity between the ages of 13-18 years were recruited to assess the relationship of blood pressure, obesity, and measures of cardiac health. Metabolic and inflammatory markers, 2-D ECHO and OGTT data were collected. The shape of the OGTT glucose response was classified based on a change from nadir to glucose-120 min of ≥ 4.5 mg/dL, and its association with cardiac health indices was calculated. R v.4.1.2 was used for analysis. Results Of the 276 individuals with available OGTT data (mean age 16.18 ± 1.70 years, 47.5% females), 39 (14.1%) had BPh curve. The individuals with BPh were lower in age (15.61 ± 1.68 vs 16.28 ± 1.68, p=0. 02), but similar in sex, BMI, BMIz and metabolic parameters. There was no difference in impaired glucose tolerance (27% [BPh] vs 15% [MPh], p=. 08). At 120 min, glucose (6.96 ± 0. 07 vs 6.31 ± 0. 07 mmol/L, p=. 05), and insulin (362.86 ± 13.69 vs 276.48 ± 13.61 uIU/mL, p=. 04) levels were higher in BPh. The glucose area under the curve (AUC) was lower in individuals with BPh (13.2 ± 1.23 vs 14.7 ± 1.16 mmol/L/hr, p &amp;lt;. 001) while the insulinogenic index (1.5 ± 3.79 vs 1.17 ± 2.74, p =. 03) and oral glucose disposition index were higher in both univariate analyses and after adjusting for age, sex and BMIz. The aortic root size was associated with the shape of the curve adjusting for age, sex and BMIz (p=. 03), but not ventricular or atrial mass, systolic or diastolic function. Conclusions There was lower proportion of individuals with BPh in this cohort of AA adolescents compared to published studies. Individuals with BPh had healthier beta-cell function indices. No significant relationship of the shape of the OGTT curve was seen with the metrics of heart structure or function at this age. Replication of results in adult cohort(s) is ongoing. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Pretransplant HOMA-β Is Predictive of Insulin Independence in 7 Patients With Chronic Pancreatitis Undergoing Islet Autotransplantation.

Background.Islet and β-cell function is intrinsic to glucose homeostasis. Pancreatectomy and islet autotransplantation (PIAT) for chronic pancreatitis (CP) treatment is a useful model for assessing islet function in the absence of immune-suppression and to perform extensive presurgical metabolic evaluations not possible from deceased donors. We recently showed that in CP-PIAT patients, preoperative islet identity loss presented with postoperative glycemic loss. Here, we examine presurgical islet function using Homeostatic Model Assessment-Beta Cell Function (%) (HOMA-β) and glycemic variables and compared them with postsurgical insulin independence and their predicted alignment with Secretory Unit of Islet Transplant Objects (SUITO) and beta cell score after transplantation (BETA-2) scores.Methods.Seven CP-PIAT patients were assessed for β-cell function metrics, including pretransplant and 6-mo posttransplant HOMA-β using insulin and C-peptide and evaluations of proposed insulin independence by SUITO and BETA-2 graft function equations. These were compared with oral glucose tolerance tests and pancreas histological samples taken at the time of transplant, examined for β-cell maturity markers.Results.Pre-PIAT, HOMA-β (60%−100%) associated with post-PIAT insulin independence. This association was only moderately supported by post-PIAT SUITO threshold scores (≥26) but robustly by BETA-2 scores (≥16.2). Appropriate posttransplant oral glucose tolerance test curves were found in those patients with normal pretransplant HOMA-β values. Preoperative low serological β-cell function was displayed by concurrent evidence of β-cell identity alterations including colocalization of insulin and glucagon, loss of urocortin-3, and increased intra-islet vimentin in patients who were insulin-dependent post-PIAT.Conclusions.These data encourage HOMA-β assessment before PIAT for estimating posttransplant insulin independence.

In Vitro and In Vivo Sucrosomial® Berberine Activity on Insulin Resistance.

Background: Berberine is a natural alkaloid with hypoglycemic properties. However, its therapeutic use is limited by a very low oral bioavailability. Here we developed a new oral formulation of berberine based on Sucrosomial® technology and tested its effect on insulin resistance. Methods: Sucrosomial® berberine was first tested in vitro in the hepatoma cell line Huh7 to assess its effect on proteins involved in glucose homeostasis and insulin resistance. The pharmacokinetics and efficacy on insulin resistance were then studied in C57BL/6 mice fed with standard (SD) and high-fat diet (HFD) for 16 weeks and treated daily during the last 8 weeks with oral gavage of Sucrosomial® berberine or berberine. Results: Sucrosomial® berberine did not affect Huh7 cell viability at concentrations up to 40 µM. Incubation of Huh7 with 20 µM of Sucrosomial® and control berberine induced glucokinase (GK) and the phosphorylation of 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), both known targets for the control of insulin resistance. In vivo, we observed an 8-fold higher plasma concentration after 3 weeks of oral administration of 50 mg/kg/day of Sucrosomial® formulation compared to berberine. HFD, compared to SD, induced insulin resistance in mice as determined by oral glucose tolerance test (OGTT). The treatment with a 6.25 mg/kg/daily dose of Sucrosomial® berberine significantly reduced the area under the curve (AUC) of OGTT (73,103 ± 8645 vs. 58,830 ± 5597 mg/dL × min), while control berberine produced the same effects at 50 mg/Kg/day (51518 ± 1984 mg/dL × min). Under these conditions, the two formulations resulted in similar berberine plasma concentration in mice. Nevertheless, a different tissue distribution of metabolites was observed with a significant accumulation of reduced, demethylated and glucuronide berberine in the brain after the oral administration of the Sucrosomial® form. Glucuronide berberine plasma concentration was higher with Sucrosomial® berberine compared to normal berberine. Finally, we observed similar increases of AMPK phosphorylation in the liver in response to the treatment with Sucrosomial® berberine and berberine. Conclusions: The Sucrosomial® formulation is an innovative and effective technology to improve berberine gastrointestinal (GI) absorption with proven in vitro and in vivo activity on insulin resistance.

Risk of gestational diabetes recurrence and the development of type 2 diabetes among women with a history of gestational diabetes and risk factors: a study among 18 clinical centers in China.

Background:Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China.Methods:A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed.Results:In 6204 participants, there are 1002 women (1002/6204, 16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02–1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01–1.61], P = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further.Conclusions:The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.

Patient-Wise Methodology to Assess Glycemic Health Status: Applications to Quantify the Efficacy and Physiological Targets of Polyphenols on Glycemic Control.

A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia—which would have been missed with traditional binary diagnostic methods—enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.

How Can We Adopt the Glucose Tolerance Test to Facilitate Predicting Pregnancy Outcome in Gestational Diabetes Mellitus?

BackgroundWe investigated how 100-g oral glucose tolerance test (OGTT) results can be used to predict adverse pregnancy outcomes in gestational diabetes mellitus (GDM) patients.MethodsWe analyzed 1,059 pregnant women who completed the 100-g OGTT between 24 and 28 weeks of gestation. We compared the risk of adverse pregnancy outcomes according to OGTT patterns by latent profile analysis (LPA), numbers to meet the OGTT criteria, and area under the curve (AUC) of the OGTT graph. Adverse pregnancy outcomes were defined as a composite of preterm birth, macrosomia, large for gestational age, low APGAR score at 1 minute, and pregnancy-induced hypertension.ResultsOverall, 257 participants were diagnosed with GDM, with a median age of 34 years. An LPA led to three different clusters of OGTT patterns; however, there were no significant associations between the clusters and adverse pregnancy outcomes after adjusting for confounders. Notwithstanding, the risk of adverse pregnancy outcome increased with an increase in number to meet the OGTT criteria (P for trend=0.011); odds ratios in a full adjustment model were 1.27 (95% confidence interval [CI], 0.72 to 2.23), 2.16 (95% CI, 1.21 to 3.85), and 2.32 (95% CI, 0.66 to 8.15) in those meeting the 2, 3, and 4 criteria, respectively. The AUCs of the OGTT curves also distinguished the patients at risk of adverse pregnancy outcomes; the larger the AUC, the higher the risk (P for trend=0.007).ConclusionThe total number of abnormal values and calculated AUCs for the 100-g OGTT may facilitate tailored management of patients with GDM by predicting adverse pregnancy outcomes.

Effects of volume-matched resistance training with different loads on glycemic control, inflammation, and body composition in prediabetic older adults.

The purpose of the investigation was to examine the influence of resistance training (RT) with equal volume and varying load on glycemic control, inflammation, and body composition in non-obese prediabetic older adults. Non-obese older adults with prediabetes were randomized into 2 groups, high-load (80% of 1RM) and low-load (40% of 1RM) RT (n = 12/group), both with the same training volume. Oral glucose tolerance test (OGTT) and blood samples were collected at baseline and again after 10weeks of RT. Fasting blood glucose (103.8 vs. 99.9mg/dL) and the area under the curve (AUC) of OGTT (0-30min) decreased significantly in older adults with prediabetes after 10weeks of volume-matched RT (p< 0.05). Serum levels of MCP-1 (138.7 vs. 98.5 pg/mL) and TNF-α (1.8 vs. 1.3 pg/mL) showed significant decrease after 10 weeks of high-load RT (p< 0.05). There were no changes in IL-10, IL-6, and CRP levels in both groups. Leptin showed significant decrease after 10weeks of low-load RT (p< 0.05). Changes in fasting glucose and AUC of OGTT (0-120min) were positively correlated with changes in MCP-1 and TNF-α (p< 0.05). Lean body mass (39.6 vs. 40.3kg) increased significantly after 10weeks of volume-matched RT (p< 0.05). Results indicate that equal-volume RT at different loads is beneficial to glycemic control and muscle growth, and high-load RT shows more prominent anti-inflammatory effects. Novelty: Short-term high-load resistance training can help older adults bring their blood sugar level back to normal. High-load resistance training attenuates aging-associated chronic inflammation.

Thirty days of combined consumption of a high-fat diet and fructose-rich beverages promotes insulin resistance and modulates inflammatory response and histomorphometry parameters of liver, pancreas, and adipose tissue in Wistar rats

ObjectiveThe aim of this study was to verify the effects of consumption of a high-fat diet (HFD) combined with fructose-rich beverages (FRT) in promoting metabolic and physiologic changes associated with insulin resistance. MethodsThirty-two male Wistar rats (250 ± 10 g) were randomly allocated into four groups (n = 8) that received either a standard diet (CON), HFD, FRT, or HFD + FRT for 30 d. Insulin sensitivity and glucose tolerance were evaluated using the insulin tolerance test (ITT) and oral glucose tolerance test (OGTT). Serum samples were used to analyze the metabolic parameters and hormone levels. Interleukin (IL)-6, IL-10, IL-1β, and tumor necrosis factor-α assays were performed in the liver, pancreas, gastrocnemius muscle, and epididymal adipose tissue by enzyme-linked immunosorbent assay. Histologic and morphometric analyses were performed on the liver, pancreas, and adipose tissues. ResultsConsumption of HFD + FRT promoted a significant increase (P < 0.05) in body weight, index adiposity, and in the area under the curve of ITT (P < 0.001) and OGTT (P < 0.001) when compared with the CON group. Consumption of FRT alone increased fasting glucose (P = 0.015), insulin (P = 0.035), and homeostasis model assessment index (P = 0.018), and these changes were of greater magnitude when FRT was combined with HFD. Moreover, the rats fed an HFD + FRT demonstrated a significant increase in lipid droplets in the liver (P < 0.001), an increase in adipocyte area, and an increase in inflammatory cytokines in the liver, pancreas, skeletal muscle, and adipose tissue. ConclusionConsumption of an HFD + FRT promotes insulin resistance, increases inflammatory cytokines, and modulates histomorphometric parameters of the liver, pancreas, and adipose tissue, typical of insulin resistance in humans.

Flat Oral Glucose Tolerance Test During Pregnancy: Maternal Characteristics and Risk for Adverse Outcomes.

Flat oral glucose tolerance test (OGTT) curve is characterized by low glucose levels, seemingly nonresponsive to glucose load. Few studies have explored flat OGTT during pregnancy and have yielded conflicting results, some suggesting risk for fetal growth restriction. This study evaluated the characteristics and perinatal outcomes of women with a flat OGTT during pregnancy. We found that a flat OGTT curve occurs in younger, leaner pregnant women. Also, flat OGTT curve was significantly associated with a male fetus and higher levels of pregnancy-associated plasma protein A at the first-trimester screening. Although flat OGTT can possibly reflect some degree of hyperinsulinemia, it is generally not associated with adverse maternal or neonatal outcomes.

NLRP3 inflammasome inhibitor CY-09 reduces hepatic steatosis in experimental NAFLD mice

AimsNon-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases. The NOD-like receptor protein 3 (NLRP3) inflammasome was suggested to be involved in the pathogenesis of NAFLD. A small-molecule named CY-09 is a new selective and direct inhibitor of the NLRP3 inflammasome. We aimed to investigate whether CY-09 is effective for the treatment of NAFLD in a high-fat diet (HFD)-induced mouse model. MethodsTwenty mice were fed by HFD for 14 weeks, and then were randomly assigned into two groups: (1) control group receiving dimethylsulfoxide (DMSO) solution; (2) CY-09 group receiving CY-09 injection. In an 8-week follow-up, oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to measure glucose metabolism. Liver steatosis was evaluated by the NAFLD activity score (NAS) and deemed as the primary outcome. ResultsThe body weight in CY-09 group was significantly lower than the DMSO control group on 27 weeks (41.0 ± 3.5 g vs. 49.7 ± 5.2 g, P = 0.014). The area under the curve (AUC) of OGTT was less in CY-09 group than that in DMSO group (35.81 ± 6.79 vs. 22.91 ± 2.58 mmol/L·hr, P = 0.004), as well as HOMA-IR (14.36 ± 3.89 vs. 8.82 ± 2.04 mmol.mIU.L-2, P = 0.023). Microscopically, liver lipid droplets dramatically improved and significantly lower NAS was observed in CY-09 group (8.25 ± 1.26 vs. 3.20 ± 0.45, P < 0.001). ConclusionCY-09 reduces hepatic steatosis in experimental NAFLD mice and CY-09 may be a potential therapeutic drug of NAFLD in clinical practice.

Targeting inhibition of CCR5 on improving obesity-associated insulin resistance and impairment of pancreatic insulin secretion in high fat-fed rodent models

Obesity is closely linked with type 2 diabetes and the effective therapies on obesity-associated diabetes are under development. The aim of this study was undertaken to investigate whether the inhibition of the augmented CCR5-mediated signaling could be a common target for treatment of obesity-associated insulin resistance and impairment of pancreatic insulin secretion in high-fat diet (HFD) fed rats and CCR5 knockout mice and also in isolated islets and RIN-m5F cells. Conducted with SD rats, HFD-induced body weight gain was significantly decreased in those combined with Maraviroc treatment, but food intake remained similar compared to control. Maraviroc also significantly improved the impaired oral glucose tolerance test (OGTT). As compared with wild-type mice, CCR5 deletion significantly attenuated the HFD-induced increases in glucose area under curve of OGTT and the value of HOMA-IR as well as plasma lipid profile. It also reversed the HFD-suppressed gene expressions of GLUT4 and IRS-1 in adipose tissue. On the other hand, the HFD-associated islet macrophage and T-cell infiltration were significantly decreased in CCR5 KO mice. H2O2 significantly suppressed glucose-stimulated insulin secretion (GSIS) is isolated islets, which were significantly reversed in those cotreated with CCR5 mAb. H2O2 failed to change GSIS in those of CCR5 KO mice. The palmitate-induced reactive oxygen species production was significantly decreased in those cotreated with CCR5 antagonist in RIN-m5F cells. Collectively, it is suggested that targeting inhibition of the CCR5 mediated inflammatory pathway could not only improve obesity-associated insulin resistance but also directly alleviate pancreatic β-cell dysfunction.