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Aim: Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)‐associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and β‐cell function in obese Chinese children with MAFLD. Methods: In total, 204 obese children (74 MAFLD) aged 4–17 years were enrolled into this study. HIC, insulin sensitivity and β‐cell function were calculated using the oral glucose tolerance test (1.75 g/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product–moment correlation coefficients. HIC and glucose homeostasis were assessed in a high‐fat diet mouse model, and liver samples were collected for molecular analysis. Results: Obese children with MAFLD exhibited significantly lower HIC (AUCC‐peptide/insulin ratio, p = 0.0019), higher insulin resistance (homeostatic model assessment of insulin resistance, p = 0.002), and increased compensatory β‐cell function (homeostatic model assessment‐β, p = 0.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (r = −0.5035, p < 0.0001) and β‐cell function (r = −0.4576, p < 0.0001). However, pancreatic β‐cell dysfunction (p = 0.046) was accompanied by future reduced HIC (p = 0.034) in children with MAFLD in prediabetes. In a high‐fat diet mouse model, MAFLD mice showed a 50% reduction in insulin‐degrading enzyme expression, consistent with the observed decrease in HIC. Conclusions: A lower HIC may offload pancreatic β‐cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized. [ABSTRACT FROM AUTHOR]

Background and Purpose: Metal‐based therapeutic agents are limited by the required concentration of metal‐based agents. Hereby, we determined if combination with 17β‐oestradiol (E2) could reduce such levels and the therapy still be effective in type 2 diabetes mellitus (T2DM). Experimental Approach: The metal‐based agent (vanadyl acetylacetonate [VAC])– 17β‐oestradiol (E2) combination is administered using the membrane‐permeable graphene quantum dots (GQD), the vehicle, to form the active GQD–E2–VAC complexes, which was characterized by fluorescence spectra, infrared spectra and X‐ray photoelectron spectroscopy. In db/db type 2 diabetic mice, the anti‐diabetic effects of GQD–E2–VAC complexes were evaluated using blood glucose levels, oral glucose tolerance test (OGTT), serum insulin levels, homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA‐IR] and homeostasis model assessment of β‐cell function [HOMA‐β]), histochemical assays and western blot. Key Results: In diabetic mice, GQD–E2–VAC complex had comprehensive anti‐diabetic effects, including control of hyperglycaemia, improved insulin sensitivity, correction of hyperinsulinaemia and prevention of β‐cell loss. Co‐regulation of thioredoxin interacting protein (TXNIP) activation by the combination of metal complex and 17β‐oestradiol contributed to the enhanced anti‐diabetic effects. Furthermore, a potent mitochondrial protective antioxidant, coniferaldehyde, significantly potentiates the protective effects of GQD–E2–VAC complexes. Conclusion and Implications: A metal complex–E2 combinatorial approach achieved simultaneously the protection of β cells and insulin enhancement at an unprecedented low dose, similar to the daily intake of dietary metals in vitamin supplements. This study demonstrates the positive effects of combination and multi‐modal therapies towards type 2 diabetes treatment. [ABSTRACT FROM AUTHOR]

The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship. To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes. Holstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose tolerance test was performed 30 days before the expected calving day. The primary outcome was insulin area under the curve (AUC), and secondary outcomes were clearance rate, half-life, and AUC for glucose, insulin, and non-esterified fatty acid concentrations. An intention-to-treat (ITT) approach using multiple imputation was employed for primary analysis, and an as-treated (AT) approach was used for secondary analysis. We demonstrated that we could successfully randomize the assignment of fetal sex to dams and test for causal effects of fetal sex on glucoregulatory outcomes using dairy cows as a model. Insulin AUC was not statistically different between groups (ITT p = 0.857, AT p = 0.874), and other outcomes were also not statistically different (p > 0.05). We demonstrated that causal effects of fetal sex on maternal outcomes can be causally tested in dairy cows. Our study did not provide statistical evidence to support an effect of fetal sex on maternal glucose-related outcomes. • Dairy cows are a suitable model to test the relationship between fetal sex and maternal health outcomes. • We demonstrate that fetal sex can be randomized using sex-sorted semen to assess causality. • Our results do not provide statistical evidence to support an effect of fetal sex on maternal glucoregulatory outcomes. [ABSTRACT FROM AUTHOR]

Background: For ages, botanical medicine has been used in the treatment of diabetes mellitus (DM). Notoginsenoside R1 (NGR1), a Panax notoginseng (Burkill) F.H.Chen metabolite, has been documented to possess antidiabetic action in vivo. However, its precise molecular mechanism of action is not clear. Objectives: We evaluated NGR1's effects on blood glucose in vivo and then evaluated in vitro whether NGR1 has effects on insulin secretion and the probable molecular pathways involved in NGR1-induced insulin secretion. Methods: Diabetes was induced inmice by streptozotocin. Glucose tolerance test was performed before and after NGR1 was administered intraperitoneally to diabetic animals for 4 weeks. Static and perifusion experiments were performed using isolated female BALB/c mouse islets. Preproinsulin (Ins) mRNA expression was measured using q-PCR. Protein expression of PI3K/Akt pathway was assessed using the fully automated Wes™ capillary-based protein electrophoresis. Results: Treatment of diabetic mice with NGR1 improved their glucose intolerance. In vitro, NGR1 increased insulin secretion in a concentrationdependent manner. NGR1 initiated the secretion of insulin at 2 mM glucose and augmented glucose-stimulated insulin secretion which was sustained throughout NGR1 perifusion. NGR1-induced insulin secretion was not altered by a voltage gated calcium channel blocker or protein kinase A inhibitor. NGR1 did not significantly modulate Ins mRNA expression. However, NGR1 significantly increased the levels of phospho-Akt and phopho-p-85. Conclusion: In conclusion, this study has shown that NGR1 ameliorates hyperglycemia in diabetic mice. NGR1 has a direct insulin secretagogue activity on mouse islets, stimulates insulin secretion at both basal and postprandial glucose concentrations, and activates PI3K/Akt pathway to induce insulin secretion. These results suggest that NGR1 may provide an alternative therapy to manage DM. [ABSTRACT FROM AUTHOR]

Objective • To explore the prognostic significance of the Glucose Disposal Index (DI) concerning unfavorable pregnancy outcomes in mothers and newborns affected by Gestational Diabetes Mellitus (GDM). Methods • Our investigation encompassed 75 GDM patients who received treatment at Anhui Mingguang People’s Hospital between January 2019 and July 2023. Subjects were divided into two groups: those with adverse pregnancy outcomes (n = 18) and those without (n = 57). Between weeks 24 and 28 of gestation, all participants underwent a 75 g Oral Glucose Tolerance Test (OGTT), and relevant details such as height, weight, and complete pregnancy information were gathered. The Insulin Sensitivity Index (ISI) and the area beneath the insulin-to-glucose curve from 0 to 120 minutes (AUC_INS120/AUC_GLU120) were computed from the 75 g OGTT findings, and their multiplication was represented as DI. Comparisons between groups were made using t tests, Wilcoxon rank-sum tests, and χ² tests. Binary logistic regression was applied to probe the relationship between DI and the risk of adverse pregnancy outcomes, and the Receiver Operating Characteristic (ROC) curve was employed to evaluate the predictive capacity of DI. Results • Statistically meaningful differences in FPG, HbA1c, and DI were noted between the groups (P < .05), whereas the difference in 2hPG was not significant (P > .05). Pearson correlation analysis revealed a negative correlation between DI and both FPG and HbA1c (P < .05). Multivariate logistic regression showed that DI (OR = 0.599) was a determining factor of adverse pregnancy outcomes (P < .05). The ROC curve disclosed an AUC of 0.837 for DI in forecasting adverse pregnancy outcomes (95% CI: 0.741-0.933), with a specificity of 82.10% and a sensitivity of 80.65% at the optimal threshold value of 2.1. Conclusion • An elevation in DI among GDM patients is closely linked to a reduced risk of adverse pregnancy outcomes, corroborating DI’s prognostic value for such outcomes in gestational diabetes. [ABSTRACT FROM AUTHOR]

Summary: The clinical data analysis found that, compared with the traditional obesity index, the waist-weight ratio (WWR) has more advantages in predicting abnormal bone mineral density in subjects with type 2 diabetes. WWR may serve as a new predictive indicator for osteoporosis in T2DM patients. Purpose: This study was designed to explore the correlation between obesity-related indices and bone mineral density (BMD) and its influencing factors in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 528 patients with type 2 diabetes were recruited. Glucose tolerance, insulin stimulation, and blood biochemical tests were conducted on all participants. All subjects underwent dual-energy X-ray bone density testing and were grouped based on the bone density results. Results: Compared with those in the normal BMD group, the waist-to-body weight ratio (WWR) and weight-adjusted-waist index (WWI) in the osteopenia and osteoporosis groups were significantly greater, while body mass index (BMI) was significantly lower (P < 0.05). The logistic regression results showed that the WWR, WWI, and BMI were independently correlated with abnormal BMD in T2DM patients (P < 0.05). WWR and the WWI were negatively correlated with the T-value of bone density in various parts of the body, while BMI was positively correlated with the T-value of bone density (P < 0.05). The area under the working characteristic curve (AUC) for T2DM patients with abnormal bone mass predicted by the WWR [0.806, 95% CI = (0.770–0.843), P < 0.001] was greater than that for patients with other obesity indicators, such as the WWI and BMI. Conclusion: We found a positive correlation between the WWR and bone density in T2DM patients. Compared with other obesity indicators, such as BMI and WWI, the WWR has a stronger discriminative ability for T2DM patients with abnormal bone density. Therefore, more attention should be given to the WWR in T2DM patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of G protein‐coupled receptor 55 (GPR55) deletion on glucose homeostasis and islet function following diet‐induced obesity. Methods: GPR55−/− and wild‐type (WT) mice were fed ad libitum either standard chow (SC) or a high‐fat diet (HFD) for 20 weeks. Glucose and insulin tolerance tests were performed at 9/10 and 19/20 weeks of dietary intervention. Insulin secretion in vivo and dynamic insulin secretion following perifusion of isolated islets were also determined, as were islet caspase‐3/7 activities and β‐cell 5‐bromo‐20‐deoxyuridine (BrdU) incorporation. Results: GPR55−/− mice fed a HFD were more susceptible to diet‐induced obesity and were more glucose intolerant and insulin resistant than WT mice maintained on a HFD. Islets isolated from HFD‐fed GPR55−/− mice showed impaired glucose‐ and pcacahorbol 12‐myristate 13‐acetate‐stimulated insulin secretion, and they also displayed increased cytokine‐induced apoptosis. While there was a 5.6 ± 1.6‐fold increase in β‐cell BrdU incorporation in the pancreases of WT mice fed a HFD, this compensatory increase in β‐cell proliferation in response to the HFD was attenuated in GPR55−/− mice. Conclusions: Under conditions of diet‐induced obesity, GPR55−/− mice show impaired glucose handling, which is associated with reduced insulin secretory capacity, increased islet cell apoptosis and insufficient compensatory increases in β‐cell proliferation. These observations support that GPR55 plays an important role in positively regulating islet function. [ABSTRACT FROM AUTHOR]

Aim: To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves β‐cell responsivity in healthy men. Methods: In a double‐blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non‐insulin–treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity. Results: Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C‐peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min). Conclusions: This outcome contrasts with the oxytocin‐induced attenuation of early postprandial glucose excursions in normal‐weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals. [ABSTRACT FROM AUTHOR]

Time-restricted eating (TRE) is a nutritional intervention that confines the daily time-window for energy intake. TRE reduces fasting glucose concentrations in non-pregnant individuals, but whether this eating protocol is feasible and effective for glycemic control in pregnancy is unknown. The aim of this randomized controlled trial was to investigate the adherence to and effect of a 5-week TRE intervention (maximum 10 h daily eating window) among pregnant individuals at risk of gestational diabetes mellitus (GDM), compared with a usual-care control group. Participants underwent 2-h oral glucose tolerance tests and estimation of body composition, before and after the intervention. Interstitial glucose levels were continuously measured, and adherence rates and ratings of hunger were recorded daily. Thirty of 32 participants completed the trial. Participants allocated to TRE reduced their daily eating window from 12.3 (SD 1.3) to 9.9 (SD 1.0) h, but TRE did not affect glycemic measures, blood pressure, or body composition, compared with the control group. TRE increased hunger levels in the evening, but not in the morning, and induced only small changes in dietary intake. Adhering to a 5-week TRE intervention was feasible for pregnant individuals with increased risk of GDM but had no effect on cardiometabolic outcomes. [ABSTRACT FROM AUTHOR]

Aims: This study was aimed at assessing the association of oral glucose tolerance test (OGTT) glucose threshold levels and the requirement of insulin therapy in twin pregnancies with gestational diabetes mellitus (GDM). Methods: In this post hoc analysis of a cohort study spanning 18 years, 446 patients with twin pregnancy and GDM (246 managed with lifestyle modification and 200 requiring pharmacotherapy) were included. We collected and evaluated maternal characteristics, as well as fasting, 1‐h, and 2‐h glucose concentrations from a standardized 75‐g OGTT. The assessment methods included logistic regression analysis, positive and negative predictive values, area under the curve (AUC), and random forest analysis. Results: The fasting (p < 0.01, OR: 1.03 [95% CI 1.01–1.05]) and 1‐h (p < 0.01; OR: 1.01 [95% CI 1.00–1.02]) glucose levels during the OGTT were significantly associated with the subsequent need for insulin therapy, with thresholds of 95 mg/dL for fasting glucose and 184 mg/dL for the 1‐h OGTT. Additionally, indications for insulin therapy were marked by thresholds of 108 mg/dL at G0, 215 mg/dL at G60, and 86 mg/dL at G120. Conclusion: Identifying threshold values for insulin therapy and risk stratification in twin pregnancy are crucial for optimal patient management. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions This study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E‐GDM).This study included 530 singleton mothers with E‐GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E‐GDM can be classified according to its management into only diet therapy until delivery (Diet E‐GDM), insulin therapy started before 24 gestational weeks (EarlyIns E‐GDM), and insulin therapy started after 24 gestational weeks (LateIns E‐GDM). We analyzed the risk factors for EarlyIns E‐GDM.Patients with EarlyIns E‐GDM had a significantly higher maternal age at delivery, pre‐pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h‐PG), and 2 h‐PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E‐GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E‐GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h‐PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82).Although further research is needed, our data suggest the importance of early insulin therapy in cases of E‐GDM with multiple abnormal OGTT values, especially with high 1 h‐PG levels and initial increase. [ABSTRACT FROM AUTHOR]

Type 2 diabetes, obesity, and several other metabolic diseases are all largely attributed to the problem known as insulin resistance. Diagnosing insulin resistance promptly and accurately is essential for adequately managing and intervening in metabolic disorders. Several diagnostic methods have been developed to assess insulin resistance. However, each method has advantages and disadvantages. The most precise test is the hyperinsulinemic-euglycemic clamp, which examines the direct impact of insulin on glucose uptake by tissues. However, it is primarily utilized in research due to its complexity and intrusiveness. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI) are the second most used Insulin resistance tests in the clinical setup. These tests are based on measuring the fasting glucose and insulin levels. The Oral Glucose Tolerance Test (OGTT), Insulin tolerance test, and the Matsuda Index are further diagnostic procedures that shed light on insulin sensitivity. The improved techniques, such as the insulin suppression test and the minimal model analysis, provide substitutes for unique clinical circumstances. Additionally, including extra measurements with these tests, like waist circumference, lipid profiles, and inflammatory markers, can improve the evaluation of insulin resistance. In summary, identifying insulin resistance is essential for the early detection and treatment of various metabolic illnesses. To make educated judgments and improve patient care, healthcare workers should be aware of the different available diagnostic tests and how they are used in each situation. Insulin resistance detection and monitoring will require further study to improve current diagnostic approaches and create novel, less invasive techniques. [ABSTRACT FROM AUTHOR]

Objective: Disorders of glucose metabolism in children with obesity are less common than in adults. There is also evidence that they may be transient. The aims of this study were to determine the prevalences of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (DM2) and its reversibility in pediatric patients with obesity and to define the factors determining the reversibility of prediabetes or progression to diabetes. Methods: Retrospective analysis included of young patients with obesity. Patients presented and were treated between 2000-2022 at a single center. Results: The study included 573 (316 girls; 55.15%) Caucasian patients with median body mass index (BMI) Z-score of 3.95 (range 2.0-9.9) and median age 13.9 (2.9-17.1) years old. OGTT results were normal in 90.8% (n=520) and signs of prediabetes occurred in 9.2% (n=53); IFG 17%, IGT 88.7%, DM 0%. Among those who underwent OGTT twice (n=53), impaired glucose regulation was present in 9.3% (n=5) (IFG 40%, IGT 80%, DM 0%) at baseline and in 14.8% subject (n=8) (IFG 25%, IGT 50%, DM 25%) at follow-up after lifestyle modification only. After 12-36 months of follow up, in those with a history of IGT, 60% reverted to normal glucose tolerance, while IFG and IGT persisted in 20% and 20%, respectively, and none progressed to DM. The risk factors for progression of glucose metabolism disorders were increase of BMI Z-score, higher insulin levels and elevated homeostatic model assessment-insulin resistance. Conclusion: IFG and IGT are common in pediatric patients with obesity, while the progression to DM2 is rare. Disorders of glucose metabolism have reversible character. [ABSTRACT FROM AUTHOR]

Aim: To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). Methods: In total, 81 women with GDM and 81 age‐matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24‐28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post‐OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA‐IR) and glucagon‐alanine index, respectively. Results: As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post‐OGTT in GDM participants (p <.001 each). Both the HOMA‐IR and the glucagon‐alanine index were higher in GDM participants. There was a weak positive correlation between HOMA‐IR and glucagon‐alanine index (r = 0.24, p =.0024). Combining the HOMA‐IR and the glucagon‐alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA‐IR and 0.751 for glucagon‐alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA‐IR and glucagon‐alanine index correlated differentially with fasting glucose, triglycerides, low‐density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. Conclusions: Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM. [ABSTRACT FROM AUTHOR]

Background: Association between liver cirrhosis (LC) and glucose intolerance has been known since long. Many studies in the past have attempted to explore the correlation of glucose metabolism disorders (GMD) with the severity of LC with mixed results (some favouring i.e. higher prevalence of GMD in more severe LC; others negating). This study was conducted to shed further light on the significance of this association. Objective: This study has been carried out with the aim of studying the correlation between GMD and the severity of LC, as determined by the Child-Turcotte-Pughe (CTP) score. Methods: 100 patients with LC admitted in medical wards were studied and tested with fasting plasma glucose (FPG), 2 h post-75 g oral glucose load plasma glucose (PPG), glycosylated haemoglobin (HbA1c) and fasting plasma insulin. They were categorized based on the severity of LC into CTP A, B or C class and then patients belonging to different classes were compared for the presence of GMD and insulin resistance (IR). Conclusion: Out of 100 patients, 6, 21 and 73 were respectively found as falling under CTP class A, B and C of LC. The frequency of diabetes mellitus (DM) was found to progressively increase with worsening grade of cirrhosis (17%-A, 24%-B and 27%-C), however this was not significant (p value 0.82). The p values for IR, GMD (pre-diabetes or DM), pre-diabetes (pre-DM) were 0.629, 0.382 and 0.189 respectively. To conclude, development of GMD and IR may be independent of the severity of LC. However more studies may be required to further study this association. [ABSTRACT FROM AUTHOR]

The aim of the present work was to gain insight into the metabolism of pigs derived from assisted reproductive technologies during their adulthood. Approximately 4h after feeding, a blood sample was taken from 3.5 year old sows born by artificial insemination (AI group, n = 7) and transfer of in vitro produced embryos (IVP group, n = 11) to determine the physiological concentrations of the main biomarkers of carbohydrates (glucose and lactate), proteins (albumin, creatinine and urea) and lipids (cholesterol and triglycerides). Four weeks later, an oral glucose tolerance test (OGTT; 1.75g glucose/kg body weight) was performed after an overnight fast and 1h of water withdrawal. Blood samples were obtained prior (T = 0 min; fasting conditions) and 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min after glucose intake. At each time point, glycemia was measured immediately using glucometer test strips, and serum was collected to determine the above metabolites along with insulin and glucagon. After OGTT, the area under the curve (AUC) between sampling times and homeostasis model assessment of insulin resistance (HOMA) indices were calculated. Under physiological conditions, the concentration of metabolites studied was similar between AI and IVP sows. In both groups, fasting decreased cholesterol and increased triglycerides and urea (P < 0.001). However, creatinine and lactate were similar in both groups under physiological and fasting conditions. The expected increase in albuminemia and decrease in glycaemia after fasting was only observed in IVP sows. OGTT revealed a different glucose curve pattern (monophasic in AI and biphasic in IVP group), a lower mean concentration of cholesterol, glucose, lactate, triglycerides in IVP compared to AI pigs (P < 0.01), and a higher mean concentration of albumin, creatinine and insulin in IVP compared to AI group (P < 0.05). On the contrary, no differences were found between groups for mean serum glucagon and urea levels, nor for glucose homeostasis indices HOMA-IR and HOMA-%B. The AUC differed between groups at several time points with larger AUC for creatinine, and smaller AUC for glucose, glucagon, and triglycerides, in IVP pigs than in AI pigs at 180–210 min (P < 0.05). In conclusion, under physiological conditions the metabolic profile of fully-grown AI and IVP sows is similar and within normal ranges. Glucose challenge revealed differences in metabolic and insulin responses between groups but with normal glucose tolerance in both cases. • Does embryonic origin (in vivo vs. in vitro) affect the metabolism of 3.5 year old sows? • Do sows respond differently under physiological conditions, fasting and oral glucose challenge (OGTT)? • In in vitro produced sows, albuminemia increased and glycaemia decreased under fasting conditions. • During OGTT, in vitro produced sows had lower mean cholesterol, glucose and triglyceride concentrations than in vivo group. • Biphasic glucose curve and high insulin concentration in in vitro group indicate normal glucose tolerance in these animals. The literature reports metabolic disturbances and a certain predisposition to insulin resistance and diabetes in individuals born from assisted reproductive technologies. Here, the metabolic profile and response to the oral glucose tolerance test were determined in in vivo and in vitro conceived sows at the age of 3.5 years. The results showed that the carbohydrate, lipid and protein profile is similar under physiological conditions, but the metabolic response is different when animals are subjected to challenging conditions such as fasting and glucose tolerance test. Therefore, the embryonic origin of pigs (vivo or vitro) should be considered when selecting sows for breeding programmes and metabolic studies. [ABSTRACT FROM AUTHOR]

The present study investigated the associations of serum gamma-glutamyl transferase (GGT), a marker of fatty liver and oxidative stress, and ALT/AST, a marker of fatty liver, with percentage trunk fat and postload glucose, insulin resistance, and β-cell function in middle-aged Japanese individuals, whose BMI averaged < 23.0 kg/m2. Pancreatic β-cell function was assessed using the disposition index calculated by a product of the insulinogenic index (IGI) and Matsuda insulin sensitivity index, a biomarker of early-phase glucose-stimulated insulin secretion and whole-body insulin sensitivity, respectively. Multivariate linear regression analyses revealed that the disposition index was associated inversely with GGT independently of percentage trunk fat, homeostasis model assessment insulin resistance (HOMA-IR), a marker of insulin resistance, and Matsuda index. When IGI was included instead of the disposition index, IGI (inversely) and HOMA-IR were associated with GGT independently of percentage trunk fat and Matsuda index. When the area under the glucose concentration curve (AUCg) during an oral glucose tolerance test was included instead of the disposition index, AUCg and HOMA-IR emerged as independent determinants of GGT. ALT/AST was associated with HOMA-IR alone. Results suggest a different pathophysiologic basis between GGT and ALT/AST in predicting diabetic risk in non-obese Japanese. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations. Biopsies were obtained from the thigh muscle, followed by an intravenous glucose tolerance test. Indices of insulin action were calculated and cardiovascular measurements, analyses of blood and muscle were performed. Whole body insulin sensitivity (SIgalvin) was positively related to expression of type I muscle fibers (r = 0.49; P < 0.001) and negatively related to resting heart rate (HR, r = −0.39; P < 0.001), which was also negatively related to expression of type I muscle fibers (r = −0.41; P < 0.001). Muscle protein expression of endothelial nitric oxide synthase (eNOS), whose activation results in vasodilation, was measured in two subsets of subjects expressing a high percentage of type I fibers (59 ± 6%; HR = 57 ± 9 beats/min; SIgalvin = 1.8 ± 0.7 units) or low percentage of type I fibers (30 ± 6%; HR = 71 ± 11; SIgalvin = 0.8 ± 0.3 units; P < 0.001 for all variables vs. first group). eNOS expression was 1) higher in subjects with high type I expression; 2) almost twofold higher in pools of type I versus II fibers; 3) only detected in capillaries surrounding muscle fibers; and 4) linearly associated with SIgalvin. These data demonstrate that an altered function of the autonomic nervous system and a compromised capacity for vasodilation in the microvasculature occur early in the development of IR. NEW & NOTEWORTHY: Insulin resistance (IR) is a risk factor for the development of several metabolic diseases. In healthy young individuals, an elevated heart rate (HR) correlates with low insulin sensitivity and high expression of type II skeletal muscle fibers, which express low levels of endothelial nitric oxide synthase (eNOS) and, hence, a limited capacity to induce vasodilation in response to insulin. Early targeting of the autonomic nervous system and microvasculature may attenuate development of diseases stemming from insulin resistance. [ABSTRACT FROM AUTHOR]

Neprilysin is a ubiquitous peptidase that can modulate glucose homeostasis by cleaving insulinotropic peptides. While global deletion of neprilysin protects mice against high-fat diet (HFD)-induced insulin secretory dysfunction, strategies to ablate neprilysin in a tissue-specific manner are favored to limit off-target effects. Since insulinotropic peptides are produced in the gut, we sought to determine whether gut-specific neprilysin deletion confers beneficial effects on insulin secretion similar to that of global neprilysin deletion in mice fed a HFD. Mice with conditional deletion of neprilysin in enterocytes (NEPGut−/−) were generated by crossing Vil-Cre and floxed neprilysin mice. Neprilysin activity was almost abolished throughout the gut in NEPGut−/− mice, and was similar in plasma, pancreas, and kidney in NEPGut−/− vs control mice. An oral glucose tolerance test was performed at baseline and following 14 weeks of HFD feeding, during which glucose tolerance and glucose-stimulated insulin secretion (GSIS) were assessed. Despite similar body weight gain at 14 weeks, NEPGut−/− displayed lower fasting plasma glucose levels, improved glucose tolerance, and increased GSIS compared to control mice. In conclusion, gut-specific neprilysin deletion recapitulates the enhanced GSIS seen with global neprilysin deletion in HFD-fed mice. Thus, strategies to inhibit neprilysin specifically in the gut may protect against fat-induced glucose intolerance and beta-cell dysfunction. [ABSTRACT FROM AUTHOR]

Previous studies have suggested a potential role of bone morphogenetic protein 6 (BMP6) in glucose metabolism, which also seems to be regulated by serotonin (5-hydroxytryptamine, 5HT), a biogenic amine with multiple roles in the organism. In this study, we explored possible interactions between BMP6, serotonin, and glucose metabolism regulation. The effect of BMP6 or 5HT on pancreatic β-cells has been studied in vitro using the INS-1 832/13 rat insulinoma cell line. Studies in vivo have been performed on mice with the global deletion of the Bmp6 gene (BMP6−/−) and included glucose and insulin tolerance tests, gene expression studies using RT-PCR, immunohistochemistry, and ELISA analyses. We have shown that BMP6 and 5HT treatments have the opposite effect on insulin secretion from INS-1 cells. The effect of BMP6 on the 5HT system in vivo depends on the tissue studied, with no observable systemic effect on peripheral 5HT metabolism. BMP6 deficiency does not cause diabetic changes, although a mild difference in insulin tolerance test between BMP6−/− and WT mice was observed. In conclusion, BMP6 does not directly influence glucose metabolism, but there is a possibility that its deletion causes slowly developing changes in glucose and serotonin metabolism, which would become more expressed with ageing. [ABSTRACT FROM AUTHOR]

Patients with diabetes require daily medication to maintain blood sugar levels. Nevertheless, the long-term use of antidiabetics can lose efficacy and cause degeneration in some patients. For long-term diabetes care, integrating natural dietary foods and medicine is being considered. This study investigated the impact of SDOs on blood sugar levels and their physiological effects on diabetic rats. We induced diabetes in male Wistar rats with STZ (50 mg/kg) and then administered an oral glucose tolerance test to determine the SDO dosage comparable to glibenclamide. The rats were divided into nine groups: normal, diabetic, and diabetic with insulin (10 U/kg), glibenclamide (0.6 mg/kg), bovine serum albumin (BSA; 200 mg/kg), soy protein isolate (200 mg/kg), or SDOs (50, 100, and 200 mg/kg). Diabetic rats administered SDOs had a higher body weight and serum insulin but a lower blood sugar than diabetic control rats. Biochemical assays indicated lower AST/SGOT, ALT/SGPT, BUN, and triglycerides but higher HDL in the SDO groups. Immunohistochemistry showed that SDOs reduced damaged islet cells, increased beta-cell size, and improved insulin levels while decreasing alpha cell size and glucagon. The vascular effects of SDOs were like those of normal control treatment and insulin treatment in diabetic rats. SDOs, a yellow silk protein, show potential for long-term diabetes care. [ABSTRACT FROM AUTHOR]

A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60 % high-fat diet for 3 months. Mice were then dosed hPNO for 24 d, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced body weight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice, but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4. [ABSTRACT FROM AUTHOR]

Introduction: Incretin-based drugs are extensively utilized in the treatment of type 2 diabetes (T2D), with remarkable clinical efficacy. These drugs were developed based on findings that the incretin effect is reduced in T2D. The incretin effect in East Asians, whose pancreatic β-cell function is more vulnerable than that in Caucasians, however, has not been fully examined. In this study, we investigated the effects of incretin in Japanese subjects. Methods: A total of 28 Japanese subjects (14 with normal glucose tolerance [NGT], 6 with impaired glucose tolerance, and 8 with T2D) were enrolled. Isoglycemic oral (75 g glucose tolerance test) and intravenous glucose were administered. The numerical incretin effect and gastrointestinally-mediated glucose disposal (GIGD) were calculated by measuring the plasma glucose and entero-pancreatic hormone concentrations. Results and discussion: The difference in the numerical incretin effect among the groups was relatively small. The numerical incretin effect significantly negatively correlated with the body mass index (BMI). GIGD was significantly lower in participants with T2D than in those with NGT, and significantly negatively correlated with the area under the curve (AUC)-glucose, BMI, and AUC-glucagon. Incretin concentrations did not differ significantly among the groups. We demonstrate that in Japanese subjects, obesity has a greater effect than glucose tolerance on the numerical incretin effect, whereas GIGD is diminished in individuals with both glucose intolerance and obesity. These findings indicate variances as well as commonalities between East Asians and Caucasians in the manifestation of incretin effects on pancreatic β-cell function and the integrated capacity to handle glucose. [ABSTRACT FROM AUTHOR]

Introduction: In the context of the increasing prevalence of metabolic diseases such as diabetes, the search for natural compounds with potential impact on glycemic regulation has become a crucial area of research. Among the numerous options available, Vaccinium corymbosum extract, commonly known as "blueberry", has emerged as a promising candidate due to its rich composition of phytochemicals with antioxidant, anti-inflammatory and hypoglycemic properties. The aim of this study was to determine the total phenolic content (TPC) and the activity of Vaccinium corymbosum ("blueberry") fruit extract on glycemia in healthy mice. Methods: The Folin-Ciocalteau method was applied in order to quantify the phenolic compounds and the BE was administered to 25 mice distributed in six groups: control, negative control, experimental-D1-D2-D3, which were administered the BE in doses of 40, 80 and 120 mg/kg b.w. respectively; and insulin group; which were subjected to the glucose tolerance test (GTT) taking blood samples after 30, 60, 120 and 180 minutes. Results: The total phenolic content (TPC) amount found in the berries was 3.79±0.06 GAE/dry weight (mg/g) and 18.96±0.28 GAE/solution (mg/L). Statistically significant differences were observed between the three doses of BE and the negative control during GTT as well as induced a significant reduction in area under the curve (AUC) compared to the negative control. Conclusions: the three doses of the BE decreased glucose levels being the dose of 40 mg/kg b.w. the one that produced a statistically significant decrease with respect to the doses of 80 and 120 mg/kg b.w. during GTT. [ABSTRACT FROM AUTHOR]

We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet (HFD) and streptozotocin (STZ) to elicit T2D were hyperglycemic. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG. Insulin secretion during the oral glucose tolerance test was impaired in T2D and REG at 10 min (p < 0.05) but the iAUC was highly variable in all groups and statistical differences were not detected (p > 0.05). β-cell mass and pancreatic insulin content in T2D and REG were 50% lower than REF (p < 0.05), whereas LOW was not significantly different. Although isolated islets from all groups responded to glucose, the absolute amount of insulin secreted by T2D and REG was markedly reduced compared with REF, while LOW islets had relatively normal secretion. In conclusion, LOW but not REG cheese enhanced β-cell recovery from HFD/STZ treatment that led to amelioration of glucose tolerance within 5 weeks. [ABSTRACT FROM AUTHOR]

Objective: The complete role of factors contributing to the pathogenesis of childhood obesity remains to be fully elucidated. Limited research has addressed trace elements in the context of child obesity. Our objective was to assess trace element and lead (Pb), copper (Cu) (are toxic metal) levels in both healthy and obese children, and to investigate the potential correlations between these elements and obesity-related anthropometric measurements, lipid profiles, as well as insulin and glucose levels. Materials and Methods: Furnace atomic absorption spectrophotometry was employed to measure the concentrations of trace elements in the serum. Additionally, fasting glucose, insulin, and lipid levels were determined in obese children (body mass index ≥ 95th percentile for age and sex), along with 50 healthy children. Only the obesity group underwent an oral glucose tolerance test (OGTT). Results: Significantly reduced levels of Fe, Mg, Zn, and Co were observed in obese children, whereas Cu, Pb, and Mn levels were elevated (P < .001, P <.001, P = .002, P = .008, P <.001, P = .001, P = .007, respectively). Significant positive correlations were found between the 2-hour glucose level in OGTT and Mn (P = .013), as well as between peak insulin and insulin levels at the 30th and 60th minutes, and Fe (P = .001, P = .025, P = .001). Conclusion: This study indicates that an imbalance in trace element levels and the accumulation of Pb may be associated with obesity, while levels of Mn and Fe may be linked to glucose intolerance. [ABSTRACT FROM AUTHOR]

Vanadium compounds are known to exert insulin-enhancing activity, normalize elevated blood glucose levels in diabetic subjects, and show significant activity in models of insulin resistance (IR). Faced with insulin resistance, the present work investigates the antidiabetic performance of a known oxidovanadium(IV)-based coordination compound—[VIVO(octd)]—and effects associated with glucocorticoid-induced insulin resistance in mice. The effects of [VIVO(octd)] were evaluated in a female Swiss mice model of insulin resistance induced by seven days of dexamethasone treatment in comparison with groups receiving metformin treatment. Biological assays such as hematological, TyG index, hepatic lipids, glycogen, oxidative stress in the liver, and oral glucose tolerance tests were evaluated. [VIVO(octd)] was characterized with 51V NMR, infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR), electronic absorption spectroscopy, and mass spectrometry (ESI–FT–MS). The [VIVO(octd)] oral treatment (50 mg/kg) had an antioxidant effect, reducing 50% of fast blood glucose (p < 0.05) and 25% of the TyG index, which is used to estimate insulin resistance (p < 0.05), compared with the non-treated group. The oxidovanadium–sulfur compound is a promising antihyperglycemic therapeutic, including in cases aggravated by insulin resistance induced by glucocorticoid treatment. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by diffuse hepatocellular steatosis due to fatty deposits in hepatocytes, excluding alcohol and other known liver injury factors. However, there are no specific drugs for the clinical treatment of NAFLD. Therefore, research on the pathogenesis of NAFLD at the cellular and molecular levels is a promising approach to finding therapeutic targets and developing targeted drugs for NAFLD. Pin1 is highly expressed during adipogenesis and contributes to adipose differentiation, but its specific mechanism of action in NAFLD is unclear. In this study, we investigated the role of Pin1 in promoting the development of NAFLD and its potential mechanisms in vitro and in vivo. First, Pin1 was verified in the NAFLD model in vitro using MCD diet-fed mice by Western Blot, RT-qPCR and immunohistochemistry (IHC) assays. In the in vitro study, we used the oleic acid (OA) stimulation-induced lipid accumulation model and examined the lipid accumulation in each group of cells by oil red O staining as well as BODIPY staining. The results showed that knockdown of Pin1 inhibited lipid accumulation in hepatocytes in an in vitro lipid accumulation model and improved lipid indices and liver injury levels. Moreover, in vivo, WT and Pin1-KO mice were fed a methionine-choline deficient (MCD) diet for 4 weeks to induce the NAFLD model. The effects of Pin1 on lipid accumulation, hepatic fibrosis, and oxidative stress were evaluated by biochemical analysis, glucose and insulin tolerance tests, histological analysis, IHC, RT-qPCR and Western blot assays. The results indicate that Pin1 knockdown significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NAFLD mice, improved glucose tolerance and alleviated insulin resistance in mice. Further studies showed that the AMPK/ACC1 signalling pathway might take part in the process by which Pin1 regulates NAFLD, as evidenced by the inhibition of the AMPK/ACC1 pathway. In addition, immunofluorescence (IF), coimmunoprecipitation (Co-IP) and GST pull-down experiments also showed that Pin1 interacts directly with ACC1 and inhibits ACC1 phosphorylation levels. Our study suggests that Pin1 promotes NAFLD progression by inhibiting the activation of the AMPK/ACC1 signalling pathway, and it is possible that this effect is achieved by Pin1 interacting with ACC1 and inhibiting the phosphorylation of ACC1. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of type 2 diabetes mellitus (T2DM) on a global scale has created a pressing demand for novel treatments. Gentianella turkestanorum (Gand.) Holub, a traditional Chinese herbal medicine, has been found to possess hypoglycemic effects. However, the mechanism of its action remains unclear. Objectives: This study was to investigate the impact and mechanism of G. turkestanorum 's water extract (WEG) in reducing insulin resistance (IR) in T2DM. Materials and Methods: Db/db mice were administered WEG for 8 weeks, during which their body weight, blood glucose (BG), oral glucose tolerance test, islet tolerance test, fasting insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein were monitored. Additionally, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in db/db mice were measured using enzyme-linked immunosorbent assay (ELISA). The study also evaluated the impact of WEG on liver injury through hematoxylin-eosin staining. The expression levels of key proteins and genes in both insulin signaling and inflammation-related pathways were detected using western blotting and real-time quantitative polymerase chain reaction. Results: WEG has the potential to regulate glycolipid metabolism, reduce inflammation, and alleviate IR. The mechanism of action may involve promoting the insulin signaling pathway and inhibiting inflammation. Conclusion: Gentianella turkestanorum could be a viable treatment option for T2DM and IR. [ABSTRACT FROM AUTHOR]

Introduction. PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Methods. Healthy adult male BALB/c mice were randomly divided into three equal groups (n = 10 in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 μl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. Result. The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in β-cell numbers between groups. Conclusion. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated. [ABSTRACT FROM AUTHOR]

Achieving diabetes remission (HbA1c<48mmol/mol without the use of anti-diabetic medication for 3 months) might not assure restoration of a normal glycemic profile [fasting blood sugar level <5.6 mmol/L and Post-Prandial (PP) blood glucose <7.8mmol/L]. The study investigates the factors associated with OGTT clearance in patients under type 2 diabetes remission. Four hundred participants who achieved remission during a one-year online structured lifestyle modification program, which included a plant-based diet, physical activity, psychological support, and medical management (between January 2021 and June 2022), and appeared for the OGTT were included in the study. OGTT clearance was defined by fasting blood glucose < 5.6 mmol/L and 2-hour post-prandial blood glucose <7.8 mmol/L post-consumption of 75g glucose solution. Of the 400 participants, 207 (52%) cleared OGTT and 175 (44%) had impaired glucose tolerance (IGT). A shorter diabetes duration (<5 years) was significantly associated with OGTT clearance (p<0.05). Pre-intervention use of glucose-lowering drugs showed no association with OGTT clearance (p<0.1). Post-intervention, the OGTT-cleared group showed significantly higher weight loss (p<0.05) and a decrease in HbA1c compared to the IGT group (p<0.05). Improvement in Insulin resistance and β-cell function was also higher in the OGTT-cleared group compared to the IGT group (p<0.05). In conclusion, clearing the OGTT is a possibility for those achieving remission through lifestyle interventions. Higher weight loss, a shorter duration of diabetes, and improvement in insulin resistance were significantly associated with OGTT clearance in participants in remission. Future randomized controlled trials with longer follow-ups may help substantiate our findings. [ABSTRACT FROM AUTHOR]

Aim: Reduced renal insulin signalling is implicated in the pathogenesis of albuminuria. We sought to investigate whether insulin action and secretion, measured before diabetes onset, are associated with the development of albuminuria after diabetes onset. Materials and Methods: Baseline body composition, insulin sensitivity by hyperinsulinaemic‐euglycaemic clamp at submaximal and maximal insulin stimulation (240 and 2400 pmol/m2/min; M‐low and M‐high), and insulin secretion by intravenous glucose tolerance test [acute insulin response (AIR)] were measured in 170 Southwestern Indigenous American adults who subsequently developed diabetes. After diabetes onset and during the median follow‐up of 13.6 years, 81 participants (48%) developed albuminuria (urine albumin‐to‐creatinine ratio ≥30 mg/g). Separate associations of M‐low, M‐high and AIR (per 1‐SD change) with the risk of albuminuria were assessed by Cox regression models adjusted for age, sex and body fat (%). Results: Participants who developed albuminuria were of similar age (26.4 ± 5.4 vs. 27.5 ± 6.1 years), sex (46% vs. 48% male), body fat (36.4 ± 7.5 vs. 35.7 ± 7.9%) and AIR [2.3 ± 0.3 vs. 2.3 ± 0.3, pmol/L (log)] as those who did not develop albuminuria but had lower insulin sensitivity [M‐low: 0.33 ± 0.08 vs. 0.36 ± 0.12, p =.03; M‐high: 0.87 ± 0.11 vs. 0.91 ± 0.12, p =.02; mg/kg‐metabolic body size/min (log)]. In separate adjusted models, lower M‐low and M‐high were both associated with an increased risk for albuminuria [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.14, 2.00, p =.004; HR 1.31, 95% CI 1.06, 1.63, p =.01), whereas AIR was not (HR 1.15, 95% CI 0.87, 1.56, p =.3). Conclusions: Lower insulin sensitivity is associated with the development of albuminuria, suggesting a role for insulin signalling in the pathogenesis of proteinuria. [ABSTRACT FROM AUTHOR]

Aim: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non‐alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. Materials and methods: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high‐fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi‐criteria approach and validated to confirm their functional relevance in vitro. Results: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA‐mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. Conclusions: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis. [ABSTRACT FROM AUTHOR]

Aim: Myo‐inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at‐risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo‐inositol‐containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. Methods: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo‐inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. Results: Higher 7‐week myo‐inositol, but not 28‐week myo‐inositol, associated with higher 1 h PG [βadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge μmol/L, p =.022] and 2 h PG [0.08 (0.03, 0.12), p =.001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7‐week myo‐inositol increase of 23.4 μmol/L with myo‐inositol supplementation. Higher 7‐week myo‐inositol associated with a lower 28‐week Stumvoll index (first phase), an approximation of insulin secretion [−0.08 (−0.15, −0.01), p =.020] but not with 28‐week Matsuda insulin sensitivity index. However, the clinical significance of a 7‐week myo‐inositol‐related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C‐peptide levels. In‐silico modelling found higher 28‐week myo‐inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7‐week myo‐inositol effects. Conclusion: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo‐inositol may slightly exacerbate later pregnancy post‐challenge glycaemia, indicating that the optimal timing for starting prenatal myo‐inositol supplementation needs further investigation. [ABSTRACT FROM AUTHOR]

Hormone-sensitive lipase (HSL) is active throughout the brain and its genetic ablation impacts brain function. Its activity in the brain was proposed to regulate bioactive lipid availability, namely eicosanoids that are inflammatory mediators and regulate cerebral blood flow (CBF). We aimed at testing whether HSL deletion increases susceptibility to neuroinflammation and impaired brain perfusion upon diet-induced obesity. HSL−/−, HSL+/−, and HSL+/+ mice of either sex were fed high-fat diet (HFD) or control diet for 8 weeks, and then assessed in behavior tests (object recognition, open field, and elevated plus maze), metabolic tests (insulin and glucose tolerance tests and indirect calorimetry in metabolic cages), and CBF determination by arterial spin labeling (ASL) magnetic resonance imaging (MRI). Immunofluorescence microscopy was used to determine coverage of blood vessels, and morphology of astrocytes and microglia in brain slices. HSL deletion reduced CBF, most prominently in cortex and hippocampus, while HFD feeding only lowered CBF in the hippocampus of wild-type mice. CBF was positively correlated with lectin-stained vessel density. HSL deletion did not exacerbate HFD-induced microgliosis in the hippocampus and hypothalamus. HSL−/− mice showed preserved memory performance when compared to wild-type mice, and HSL deletion did not significantly aggravate HFD-induced memory impairment in object recognition tests. In contrast, HSL deletion conferred protection against HFD-induced obesity, glucose intolerance, and insulin resistance. Altogether, this study points to distinct roles of HSL in periphery and brain during diet-induced obesity. While HSL−/− mice were protected against metabolic syndrome development, HSL deletion reduced brain perfusion without leading to aggravated HFD-induced neuroinflammation and memory dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the effects of fasting for 48 h on the evoked insulin and glucose responses in males and females, and to explore factors such as stress and estrogen levels that might influence these responses. Methods: Healthy, nonobese male (n = 14) and female (n = 14) subjects underwent 48-h fasting trial. Changes in glucose tolerance and insulin levels in response to the oral glucose tolerance test, subjectively perceived stress and catecholamine concentrations were measured in all participants. Estrogen levels were also measured in the female participants during the 48-h fast. Results: Glucose area under the curve (AUC) values increased similarly in both sexes after 48-h fasting (P < 0.05), but females displayed a greater rise in insulin AUC values than males (P < 0.05). Fasting increased plasma epinephrine concentrations in both sexes (P < 0.05), whereas plasma norepinephrine concentrations and subjective stress increased only in females (P < 0.05). Plasma 17-β-estradiol concentrations in females decreased after fasting (P < 0.05). Conclusion: Fasting for 48 h induced a similar glucose intolerance in females and males, despite decreased 17-β-estradiol levels and greater psychological and physiological stress in females. These differences represent a plausible explanation for the gender-based differences observed in insulin responses. Trial registration: Retrospectively registered on ClinicalTrials.gov (NCT05545943) in September 19, 2022. [ABSTRACT FROM AUTHOR]

DPP4 inhibitors are widely prescribed as treatments for type 2 diabetes. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses. Sitagliptin (100 mg) was administered to 47 healthy volunteers. Several endpoints were measured to assess clinically relevant responses – including the effect of sitagliptin on glucose and insulin levels during an oral glucose tolerance test (OGTT). This pilot study confirmed that sitagliptin (100 mg) decreased the area under the curve for glucose during an OGTT (p = 0.0003). Furthermore, sitagliptin promoted insulin secretion during the early portion of the OGTT as reflected by an increase in the ratio of plasma insulin at 30 min divided by plasma insulin at 60 min (T30:T60) from mean ± SEM 0.87 ± 0.05 to 1.62 ± 0.36 mU/L (p = 0.04). The magnitude of sitagliptin's effect on insulin secretion (as judged by the increase in the T30:T60 ratio for insulin) was correlated with the magnitude of sitagliptin‐induced increase in the area under the curve for intact plasma GLP1 levels during the first hour of the OGTT. This study confirmed previously reported sex differences in glucose and insulin levels during an OGTT. Specifically, females exhibited higher levels of glucose and insulin at the 90–180 min time points. However, we did not detect significant sex‐associated differences in the magnitude of sitagliptin‐induced changes in T30:T60 ratios for either glucose or insulin. In conclusion, T30:T60 ratios for insulin and glucose during an OGTT provide useful indices to assess pharmacodynamic responses to DPP4 inhibitors. [ABSTRACT FROM AUTHOR]

Purslane (P), chard (CHA), and chicory (CHI) leaf extracts are individually and traditionally used in the treatment of diabetes mellitus. Polyphenols, flavonoids, the polyphenolic profile of the extracts, and their antioxidant activity were determined. This study evaluated the antidiabetic activity of combinations of these extracts in streptozotocin-induced diabetic rats. Diabetic groups were administered orally and daily for 40 days with the investigated extracts at 250 mg/kg body weight (b.w.) or metformin (100 mg/kg b.w.) as a drug. Fasting blood glucose, oral glucose tolerance, insulin, and fructosamine were assessed. The combined extracts with high levels of P or CHI exerted potent hypoglycemic activity compared with metformin in addition to the restoration of the histopathological changes in the liver and pancreas of diabetic rats to a near-normal state. Therefore, these combined extracts could be developed as natural drugs for diabetes. [ABSTRACT FROM AUTHOR]

Background: Olanzapine causes alterations in lipid and glucose metabolism, indicated by weight gain, and altered metabolic profiles. Hesperidin has been related to numerous positive health benefits including improvements in cardiovascular and metabolic function making it a potentially suitable candidate to counteract the negative effects of olanzapine treatment. Hence the purpose of the study is to investigate the effect of hesperidin on olanzapine-induced weight gain, and associated lipid and glucose metabolic dysfunctions in female Sprague Dawley rats. Materials and Methods: Olanzapine (2 mg/kg b.i.d. i.p.) was administered for 28 days to induce weight gain, dyslipidemia and insulin resistance in rats. Hesperidin was tested at doses of 50, 100, 200 mg/kg p.o. over 28 days. Body weight, food intake, and water intake were noted daily. Locomotor activity was recorded weekly. Novel object recognition test, Oral glucose tolerance test, and Homeostatic Model Assessment for Insulin Resistance and antioxidant biomarkers were measured followed by histopathological examination. Results and Discussion: Treatment with hesperidin notably reduced the weight gain and hyperphagia brought on by olanzapine administration. Significant improvement in locomotor activity was observed upon hesperidin administration. Further, hesperidin resulted in a significant improvement in the discrimination ratio in the Novel object recognition test. Administration of hesperidin significantly reduced the glucose intolerance, insulin resistance and dyslipidemia induced by olanzapine treatment. Furthermore, leptin and adiponectin levels were significantly improved upon hesperidin administration. Additionally, there was a significant improvement in anti-oxidant biomarkers followed by amelioration of histological examination. Conclusion: In conclusion, it was found that hesperidin reduced weight gain, and improved lipid, and glucose dysregulation caused by olanzapine administration. Additionally, it mitigates olanzapine-induced changes in plasma levels of leptin, and adiponectin. Hesperidin also improved cognitive behavior in olanzapine-treated rats. [ABSTRACT FROM AUTHOR]

Efficient and accurate methods to estimate insulin sensitivity (SI) and b-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk. [ABSTRACT FROM AUTHOR]

Improved b-cell function seems to be essential for better glucose homeostasis after Roux-en-Y gastric bypass but is less studied after sleeve gastrectomy (SG). We evaluated the effects of SG on b-cell function in obese patients with diabetes (DM group) and without (control group) in response to both oral and intravenous glucose stimulation. The DM group demonstrated impaired insulin sensitivity and insulin response to glucose before surgery. The insulin sensitivity index of both groups significantly improved after SG. In addition, the insulin response to glucose (early insulinogenic index in oral glucose tolerance test and acute insulin response to glucose in an intravenous glucose tolerance test) increased in the DM group but decreased in the control group. As a result, b-cell function improved significantly in both groups after SG since the disposition index (DI) increased in both. However, the DI of the DM group was not restored to the level of control group up to 1 year after SG. Our results support that obese patients, with and without diabetes, could benefit fromSG in b-cell function. For obese patients at risk for or who have been diagnosed with diabetes, interventions should be recommended early to preserve or restore b-cell function, and SG could be an effective choice. Further studies are needed for long-termeffects. [ABSTRACT FROM AUTHOR]

Purpose: 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. Patients and Methods: 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). Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

For 100 years, the Intravenous glucose tolerance test (IVGTT) has been used extensively in researching the pathophysiology of diabetes mellitus and AIRg—the IVGTT-induced acute insulin response to the rapid rise in circulating glucose—is a key measure of insulin secretory capacity. For an effective evaluation of AIRg, IVGTT glucose loading should be adjusted for glucose distribution volume (gVOL) to provide an invariant, trend-free immediate rise in circulating glucose (ΔG0). Body weight-based glucose loads have been widely used but whether these achieve a trend-free ΔG0 does not appear to have been investigated. By analysing variation in AIRg, ΔG0 and gVOL with a range of IVGTT loads, both observed and simulated, we explored the hypothesis that there would be an optimum anthropometry-based IVGTT load calculation that, by achieving a trend-free ΔG0, would not compromise evaluation of AIRg as an index of beta cell function. Data derived from patient and research volunteer records for 3806 IVGTT glucose and insulin profiles. Among the non-obese, as gVOL rose, weight increased disproportionately rapidly. Consequently, the IVGTT glucose load needed for an invariant ΔG0 was progressively overestimated, accounting for 47% of variation in AIRg. Among the obese, ΔG0 was trend-free yet AIRg increased by 11.6% per unit body mass index, consistent with a more proportionate increase in weight with gVOL and a hyperinsulinaemic adaptation to adiposity-associated insulin resistance. Simulations further confirmed our hypothesis by demonstrating that a body surface area-based IVGTT load calculation could provide for a more generally invariant IVGTT ΔG0. [ABSTRACT FROM AUTHOR]

BACKGROUND: Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes. Static exercise can effectively improve skeletal muscle insulin resistance, but the mechanism remains unclear. OBJECTIVE: To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (AKT)/glucose transporter (GLUT4) signaling pathway. METHODS: After 1 week of adaptive feeding, 7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet, while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection. Twenty-four mice were successfully modeled and they were randomly divided into model group (n=8), metformin group (n=8) and static exercise group (n=8), which continued to be fed high-fat diet. The metformin group was given 200 mg/kg metformin dissolved in normal saline (2 ml/kg) by gavage, once a day, for 6 weeks. The static exercise group was given normal saline daily by gavage and carried out static exercise, 30 minutes a day, 6 days per week. The model group was given the same dose of normal saline daily by gavage without exercise intervention. After the intervention, the fasting blood glucose of each group was detected, the intraperitoneal glucose tolerance test was performed, and the area under the glycemic curve was calculated. Glycosylated hemoglobin, serum insulin, insulin resistance index were detected by ELISA. Total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein were detected using biochemical methods. The mRNA expression levels of PI3K, AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR. Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining, and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION: Compared with the blank group, fasting blood glucose, glycosylated hemoglobin, area under the glycemic curve, insulin resistance index, total cholesterol, triglyceride and low-density lipoprotein levels were significantly increased in the model group (P < 0.01, P < 0.05). Whereas, these indicators were significantly lower in the static exercise and metformin group than the model group (P < 0.01, P < 0.05). Compared with the blank group, serum insulin and high-density lipoprotein levels were significantly declined in the model group (P < 0.01) and the mRNA expression of PI3K, AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced (P < 0.01). These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group (P < 0.01). Compared with the blank group, the muscle fibers in the model group were disordered, and the muscle cells atrophied and the muscle fiber gap widened. The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group (P < 0.01). Compared with the model group, atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group, and the cross-sectional area of muscle fiber was significantly increased in both groups (P < 0.01). These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K, AKT and GLUT4 mRNA in skeletal muscle tissue, thereby improving the morphology and function of skeletal muscle tissue, alleviating insulin resistance and regulating glucose homeostasis. [ABSTRACT FROM AUTHOR]

Background: Elevated levels of somatostatin blunt glucagon counterregulation during hypoglycemia in type 1 diabetes (T1D) and this can be improved using somatostatin receptor 2 (SSTR2) antagonists. Hypoglycemia also occurs in latestage type 2 diabetes (T2D), particularly when insulin therapy is initiated, but the utility of SSTR2 antagonists in ameliorating hypoglycemia in this disease state is unknown. We examined the efficacy of a single-dose of SSTR2 antagonists in a rodent model of T2D. Methods: High-fat fed (HFF), low dose streptozotocin (STZ, 35 mg/kg)-induced T2D and HFF only, nondiabetic (controls-no STZ) rats were treated with the SSTR2 antagonists ZT-01/PRL-2903 or vehicle (n = 9–11/group) 60 min before an insulin tolerance test (ITT; 2–12 U/kg insulin aspart) or an oral glucose tolerance test (OGTT; 2 g/kg glucose via oral gavage) on separate days. Results: This rodent model of T2D is characterized by higher baseline glucose and HbA1c levels relative to HFF controls. T2D rats also had lower c-peptide levels at baseline and a blunted glucagon counterregulatory response to hypoglycemia when subjected to the ITT. SSTR2 antagonists increased the glucagon response and reduced incidence of hypoglycemia, which was more pronounced with ZT01 than PRL-2903. ZT-01 treatment in the T2D rats increased glucagon levels above the control response within 60 min of dosing, and values remained elevated during the ITT (glucagon Cmax: 156 ± 50 vs. 77 ± 46 pg/mL, p < 0.01). Hypoglycemia incidence was attenuated with ZT-01 vs. controls (63% vs. 100%) and average time to hypoglycemia onset was also delayed (103.1 ± 24.6 vs. 66.1 ± 23.6 min, p < 0.05). ZT-01 administration at the OGTT onset increased the glucagon response without exacerbating hyperglycemia (2877 ± 806 vs. 2982 ± 781), potentially due to the corresponding increase in c-peptide levels (6251 ± 5463 vs. 14008 ± 5495, p = 0.013). Conclusion: Treatment with SSTR2 antagonists increases glucagon responses in a rat model of T2D and results in less hypoglycemia exposure. Future studies are required to determine the best dosing periods for chronic SSTR2 antagonism treatment in T2D. [ABSTRACT FROM AUTHOR]

N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays antidiabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in a gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with a high-fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to establish the GDM model. Pregnant mice were treated with 0.3% or 1% MNAM during gestation. MNAM supplementation in CHOW diet and HFD both impaired glucose tolerance at gestational day 14.5 without changes in insulin tolerance. However, MNAM supplementation reduced hepatic lipid accumulation as well as mass and inflammation in visceral adipose tissue. MNAM treatment decreased GLUT4 mRNA and protein expression in skeletal muscle, where NAD+ salvage synthesis and antioxidant defenses were dampened. The NAD+/sirtuin system was enhanced in liver, which subsequently boosted hepatic gluconeogenesis. GLUT1 protein was diminished in placenta by MNAM. In addition, weight of placenta, fetus weight, and litter size were not affected by MNAM treatment. The decreased GLUT4 in skeletal muscle, boosted hepatic gluconeogenesis and dampened GLUT1 in placenta jointly contribute to the impairment of glucose tolerance tests by MNAM. Our data provide evidence for the careful usage of MNAM in treatment of GDM. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease and diabetes always coexist. The relationship of fatty liver and hyperglycemia is not clear. We studied the influence of hyperglycemia on triglyceride (TG) accumulation in the liver and explored its possible mechanisms. SD rats were divided into three groups: Group A (sham operation control), Group B (partially pancreatectomized rats), and Group C (partially pancreatectomized rats treated with insulin). At 4 weeks after surgery, pancreatic weights and liver TG contents were measured. Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed. The gene expression of sterol regulatory element-binding protein1c (SREBP-1c), carbohydrate regulatory element-binding protein (ChREBP), fatty acid synthase(FAS), carnitine palmitoyltransferase 1 (CPT-1), and fibroblast growth factor 21 (FGF21) was determined by real-time PCR. Compared with Group A, postprandial glucose increased significantly; the concentrations of insulin and C-peptides, pancreatic weights and serum FGF21 levels were decreased, liver TG was increased significantly in Group B, and insulin treatment improved these changes. Compared with Group A, the gene expressions of FGF21, CPT-1 and FAS in the liver were decreased in Group B (all p<0.05). Compared with Group B, the gene expressions of FGF21, FAS, ChREBP, SREBP-1c and CPT-1 in the liver in Group C were all increased significantly (p<0.05, respectively). Hyperglycemia induced by partial pancreatectomy could lead to increased liver TG. Insulin treatment could decrease glucose levels and improve fatty liver, and genes related to lipid metabolism may play a role in this process. [ABSTRACT FROM AUTHOR]

Aims: Bespoke glycaemic control strategies following antenatal corticosteroids for women with diabetes in pregnancy (DIP) may mitigate hyperglycaemia. This study aims to identify predictive factors for the glycaemic response to betamethasone in a large cohort of women with DIP. Methods: Evaluation of a prospective cohort study of 347 consecutive DIP pregnancies receiving two doses of 11.4 mg betamethasone 24 h apart between 2017 and 2021 and treated with the Pregnancy‐IVI intravenous insulin protocol. Regression modelling identified factors associated with maternal glycaemic time‐in‐range (TIR) and maternal insulin requirements following betamethasone. Factors associated with neonatal hypoglycaemia (glucose <2.6 mmol/L) in infants born within 48 h of betamethasone administration (n = 144) were investigated. Results: The mean maternal age was 31.9 ± 5.8 years, with gestational age at betamethasone of 33.5 ± 3.4 weeks. Gestational diabetes was present in 81% (12% type 1; 7% type 2). Pre‐admission subcutaneous insulin was prescribed for 63%. On‐infusion maternal glucose TIR (4.0–7.8 mmol/L) was 83% [IQR 77%–90%] and mean on‐IVI glucose was 6.6 ± 0.5 mmol/L. Maternal hypoglycaemia (<3.8 mmol/L) was uncommon (0.47 h/100 on‐IVI woman hours). Maternal glucose TIR was negatively associated with indicators of insulin resistance (type 2 diabetes, polycystic ovary syndrome), late‐pregnancy complications (pre‐eclampsia, chorioamnionitis) and the 1‐h OGTT result. Intravenous insulin requirements were associated with type of diabetes, pre‐eclampsia and intrauterine infection, the 1‐h OGTT result and the timing of betamethasone administration. Neonatal hypoglycaemia was associated with pre‐existing diabetes but not with measures of glycaemic control. Conclusion: An intravenous infusion protocol effectively controls maternal glucose after betamethasone. A risk‐factor‐based approach may allow individualisation of therapy. [ABSTRACT FROM AUTHOR]

Objective Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia. Study Design Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples. Results Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (β = − 0.63% 95% CI [−0.8, −0.6] p < 0.001) and remained stable between V2 and PP (β = − 0.04% [−0.3, 0.2] p = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = − 0.5, p = 0.0001; V2 rho = − 0.4, p = 0.006), but not PP (rho = − 0.15, p = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations. Conclusion %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women. Key Points Changes in %GAlb extending to the postpartum period have not been described. %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values. Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women. [ABSTRACT FROM AUTHOR]

Objective: The research aimed to compare serum levels of fasting plasma glucose, 2hrpp, fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and waist-to-height ratio in individuals with a diabetic background. Study Design: Cross-sectional Observational draft. Setting: District Headquarters Hospital, Gujranwala. Period: December 22, 2020, to December 22, 2022. Material & Methods: Overall, 80 healthy participants, 20-50 years old, were recruited and graded into two groups based on gender. Group A comprised males, and Group B comprised females. All participants demonstrated normal glucose tolerance centered on the oral glucose tolerance test. Results: Females exhibited significantly higher mean levels of fasting plasma glucose (p=0.01), fasting plasma insulin (p=0.004), and Homeostasis Model Assessment of Insulin Resistance (p=0.007) compared to males. Homeostasis Model Assessment of Insulin Resistance and waist-to-height ratio exhibited a positive correlation (p=0.001). Conclusion: Females with a positive family history may present an amplified threat of Type 2 Diabetes Mellitus. [ABSTRACT FROM AUTHOR]