Improved Fasting Glucose Research Articles

Therapeutic Potential of Ginger Ethanolic Extract, Ginger-Loaded Chitosan ‎Nanoparticles, and Chitosan Nanoparticles in Induced Type 2 Diabetes Mellitus in Dogss in Induced Type 2 Diabetes Mellitus in Dogs

Type 2 diabetes mellitus (T2DM) in dogs is a complex, multifactorial disease that is characterized by chronic hyperglycemia and insulin resistance. Current therapeutic options are often limited by side effects and variable efficacy, highlighting the need for more effective and safer treatments. This study assessed the therapeutic potential of ginger ethanolic extract (GEE), GEE-loaded chitosan nanoparticles (GEE-CNPs), and chitosan nanoparticles (CNPs) against T2DM in dogs. Twenty adult local breed mongrel dogs of both sexes, aged 7 to 13 months, with an average body weight of 10.4±0.76 kg, were included. The dogs were allocated into five groups (n=4 each): a non-diabetic, untreated Negative Control group, and four diabetic treatment groups, following T2DM induction via a single intravenous alloxan-nicotinamide injection. Each treatment group received daily oral administrations of either saline (Positive Control), GEE, GEE-CNPs, or CNPs at a dosage of 81.7 mg/kg BW over 45 days. Serum glycemic status (fasting serum glucose, insulin, and insulin resistance) was ‎recorded at baseline and on days 7, 14, 21, 28, 35, 42, and 45 post-treatments. ‎Additionally, on day 45, serum lipid profiles, liver function indicators (alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], and bilirubin), and ‎markers of antioxidant status (glutathione [GSH] and malondialdehyde [MDA]) were assessed.‎ The results showed that dogs in the diabetic Positive Control group ‎exhibited ‎hyperglycemia, dyslipidemia‎, liver ‎dysfunction, and elevated ‎oxidative stress markers, ‎‎underscoring the severe impact of T2DM. Compared to the diabetic Positive Control, oral GEE, GEE-CNPs, and CNPs ‎treatments significantly (P<0.05) improved ‎fasting glucose levels, insulin sensitivity, lipid profiles (reduced total cholesterol, ‎triglycerides, and LDL-C), liver function markers, and antioxidant status, indicating ‎enhanced metabolic health and reduced oxidative stress. The findings suggest that GEE, GEE-CNPs, and CNPs offer potential as therapeutic agents for T2DM in dogs, demonstrating ‎significant benefits in glycemic control, lipid normalization, liver function, and oxidative ‎stress reduction. Further investigations with larger cohorts and longer durations are ‎recommended to confirm these results and ascertain the clinical applicability and safety of ‎these natural remedies in managing canine diabetes‎‎‎.

DASH Diet Versus Intermittent Fasting on Insulin Resistance in NAFLD Patients

objectives: To compare between intermittent fasting and DASH diet on glycemic profile in non-alcoholic fatty liver patients. Methods:60 (men and women) prediabetic nonalcoholic fatty liver patients participated in this study; assigned randomly to three groups: Group (A): intermittent fasting time-restricted feeding (TRF) subjects consumed 100 % of their energy needs in an 8 hours period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. schedule (8-hr daily eating period, the remaining 16 hours per 24-hour period made up the fasting period). Group (B): the dietary approach to stop hypertension (DASH) subjects consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. (12-hr eating period). Group (C): control group; all subjects didn’t follow any diet regimen or calorie deficit. all participants subjected to 30 minutes moderate aerobic exercise on treadmill. Subjects tested before and after 8 weeks of the study. Results: The nonalcoholic fatty liver patients in Group B received DASH diet program more improved fasting glucose reduction percentage (18.25%), followed by patients in Group A (14.79%) received intermittent fasting program, and then those in Group C (2.55%) control group & Group B received DASH diet program more improved HOMA IR reduction percentage (62.88%), followed by patients in Group A (45.23%) received intermittent fasting program, and then those in Group C (6.77%) received control group. Conclusion; both Dash & IF are effective therapeutic approach to control insulin resistance in NAFLD patients, prevention strategy for diabetes type 2.

Diosgenin Alleviates Obesity-Induced Insulin Resistance by Modulating PI3K/Akt Signaling Pathway in Mice Fed a High-Fat Diet.

Obesity is a global medical issue that can be effectively treated by relieving adipose inflammation and subsequent insulin resistance. Diosgenin (DIOS) has various effects as a steroidal saponin in inflammatory disorders. This study explored the effects and mechanism of DIOS on adipose inflammation and insulin sensitivity, both in silico and in vivo. The high-fat diet-induced obesity model in C57BL/6 mice was divided into five groups: normal chow (NC), high-fat diet (HFD), HFD with atorvastatin 10 mg/kg (AT), HFD with DIOS 100 mg/kg (DIOS 100), and HFD with DIOS 200 mg/kg (DIOS 200). Each group underwent an oral intervention for seven weeks. DIOS significantly suppressed weight gain in the body, liver, and epididymal fat pads. Additionally, it significantly improved fasting glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance test results, and reduced the proportion of total and M1 adipose tissue macrophages. Significant changes were shown in mRNA expression of janus kinase 2 (JAK2), insulin receptor (INRS), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), all of which exhibited high binding affinity in the in silico. Safety indices, including aspartate aminotransferase (AST), alanine transaminase (ALT), and creatinine level indicated the preventive effects of DIOS. In conclusion, DIOS improves insulin resistance and obesity-associated inflammation via the PI3K/Akt signaling pathway.

The effect of microbiome-modulating therapeutics on glucose homeostasis in metabolic syndrome: A systematic review, meta-analysis, and meta-regression of clinical trials

BackgroundMetabolic syndrome (MetS) is a chronic disorder featuring overweight/obesity, high blood pressure, and dysfunction of lipid and carbohydrate metabolism. Microbiome-modulating probiotics, prebiotics, synbiotics and fecal microbiota transplant (FMT) are promising adjunct therapies for improving parameters of glucose homeostasis and insulinemia. MethodsWe conducted a comprehensive systematic review, meta-analyses, and meta-regressions to investigate the effect of the abovementioned microbiome therapies on various biomarkers after screening clinical trials published through April 2023. We pooled data using random effects meta-analyses, reporting them as mean differences (MDs) with 95 % confidence intervals (CIs), and conducting univariate linear model meta-regressions. ResultsData from 21 trial comparisons across 19 studies (n = 911) revealed that, compared to placebo/control, microbiome-modulating therapies were associated with statistically significant changes in fasting plasma glucose (MD: 4.03 mg/dL [95%CI: 6.93; −1.13]; p effect = 0.006, I2 = 89.8 %), and fasting insulin (MD: 2.56 μU/mL [95%CI: 4.28; −0.84]; p effect = 0.004, I2 = 87.9 %), but not insulin resistance or sensitivity indices and HbA1c. Age, baseline BMI, baseline biomarker value, pro/synbiotic dosage, trial duration, nutraceutical type, and WHO region were factors affecting the efficacy of these interventions at producing changes in biomarkers, signaling the potential role of personalized precision medicine adjunct therapy for deranged glucose homeostasis in patients with MetS. Nevertheless, presence of heterogeneity calls for further investigation before their clinical application. ConclusionsProbiotics, prebiotics, synbiotics and FMT supplementation improved fasting glucose and insulin in patients with MetS. Further large-scale and high-quality trials are required before potential clinical applications.

Effects of Tirzepatide vs Semaglutide on β-cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test.

In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood. To evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data. A 28-week double-blind, randomized, placebo-controlled trial. Two clinical research centers in Germany. Patients with type 2 diabetes treated with metformin. Tirzepatide 15 mg, semaglutide 1 mg, placebo. Glycemic control, model-derived β-cell function indices including insulin secretion rate (ISR) at 7.2-mmol/L glucose (ISR7.2), β-cell glucose (β-CG) sensitivity, insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio. Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < 0.01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < 0.01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < 0.01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < 0.05), showing improved β-CG responsiveness. MMTT-derived β-CG sensitivity was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < 0.01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment. These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression.

Comparison of Metabolic Risk Factors Based on the Type of Physical Activity in Korean Adolescents: Results from a Nationwide Population-Based Survey.

Physical activity (PA) is associated with a favorable metabolic risk profile in adults. However, its role in adolescents remains unclear. In this study, using data (2019-2021) from the 8th Korea National Health and Nutrition Examination Survey, we investigated the optimal exercise type for preventing metabolic complications in adolescents. A total of 1,222 eligible adolescent participants (12-18-year-old) were divided into four groups as follows: aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (CE), and no exercise (NE). Daily PA was assessed using the international PA questionnaire. Blood samples were collected to measure lipid, glucose, and insulin levels. Additionally, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglyceride-glucose (TyG) indices were measured. Multivariate regression analysis was used to compare the metabolic risk factors across the PA groups before and after propensity score matching (PSM) adjustment for confounding variables. The CE group exhibited improved fasting glucose levels, lower TyG index, reduced white blood cell count, and higher high-density lipoprotein (HDL) cholesterol levels than the NE group. The RE group exhibited lower mean blood pressure, triglyceride, fasting insulin, HOMA-IR, TyG index and a reduced risk of metabolic syndrome than the NE group. The AE group had higher total and HDL cholesterol levels. In detailed comparison of the AE and RE groups, the RE group consistently exhibited favorable metabolic parameters, including lower blood pressure and total and low-density cholesterol levels, which persisted after PSM. These findings highlight the positive effects of PA on cardiovascular risk factors in adolescents. Thus, RE may have a more favorable metabolic effect than AE. Further studies are needed to validate the benefits of exercise according to the exercise type.

Effect of Ramadan Fasting on Blood Glucose Level in Pregnant Women with Gestational and Type 2 Diabetes.

Pregnant women with diabetes are strongly advised against Ramadan fasting and have religious exemption, but a large proportion still choose to fast. Unfortunately, there is little information about glycemic control in these patients. This study aims to determine the fasting and postprandial blood glucose levels and to predict the risk factors for hypoglycemia in pregnant women with type 2 diabetes mellitus (DM) and gestational DM (GDM) who fast during Ramadan. A prospective cohort research was conducted at a single tertiary hospital between 2021 and 2023 on 70 pregnant women with GDM (n = 53) and type 2 DM (n = 17) in their second and third trimester. Their fasting and postprandial blood glucose levels during Ramadan were compared to those of the previous month, and hypoglycemia was defined as blood glucose levels less than 60 mg/dl. Binary regression was used to predict the risk variables for hypoglycemia. The GDM and type 2 DM groups were similar in terms of age, parity, number of fasting days, and number of daily fasting hours. Only 26.9% of the women who were permitted to fast were given special instructions for Ramadan fasting. Dietary intervention was more common in the GDM group, whereas insulin and metformin treatment were more common in the type 2 DM group. The fasting glucose level decreased significantly after Ramadan fasting in both groups, from 92.5 (17.4) mg/dl to 90 (17.13) mg/dl (p = 0.033). However, there were a significantly higher number of hypoglycemia events in the type 2 DM group. Further, type 2 DM was identified as a risk factor for hypoglycemia (OR = 6.23; 95% CI = 1.04-37.54; P = 0.046. The present findings indicate that Ramadan fasting may improve fasting glucose control. In addition, type 2 DM was identified as a risk factor for hypoglycemia.

The potential effect of ambrisentan as monotherapy and combined with tadalafil on diabetic erectile dysfunction in rats.

This study investigated the role of ambrisentan; the selective endothelin type-A receptor (ETAR) blocker on experimental diabetic erectile dysfunction in rats. Eighty-four adult male Sprague Albino rats were divided randomly into 7 groups. Three control groups received 1 mL saline, 0.2 mg/kg/d ambrisentan and 1.5 mg/kg/d tadalafil, respectively orally for 4 weeks. The remaining four groups were fed high fat diet for 14 days. Diabetes was induced by a single intra-peritoneal injection of 40 mg/kg streptozotocin. After 72 h, diabetes was confirmed by plasma glucose level ⩾250 mg/dL. Diabetic rats were divided randomly into four groups, numbered from 4 to 7. The fourth group was the diabetic-control group, while the fifth and sixth groups received ambrisentan and tadalafil respectively. The seventh group received a combination of both drugs. Treatment continued for 4 weeks then, copulatory, intracavernous pressure measurement, and laboratory tests were conducted. In diabetic rats, ambrisentan and tadalafil improved fasting glucose, insulin, insulin resistance, testosterone, nitric oxide, and rho kinase (ROCK) values compared to diabetic group with the maximum improvement achieved in ambrisentan/tadalafil group (p < 0.05). Ambrisentan also enhanced ICP and improved latency to erection and number of mounts with a tolerable SBP. Yet, ambrisentan/tadalafil combined therapy resulted in deterioration in SBP with consecutive worsening in ICP and mating indices. Ambrisentan showed significant therapeutic potential to prevent and improve diabetic ED in rats comparable to tadalafil.

Blended extract of oat, sorghum, adzuki bean, finger millet, and proso millet improved hyperglycemia and insulin resistance in the streptozotocin-nicotinamide-induced diabetic rats.

Grains contain bioactive components that potentially have protective effects on chronic diseases such as diabetes. The anti-diabetic effects of blended grain ethanol extract (BGE) were evaluated in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. BGE was prepared by mixing oat, sorghum, adzuki bean, finger millet, and proso millet (30:30:15:15:10). The rats were assigned into four groups, normal control, diabetic model control (DM), STZ-NA rats administered 200mg/kg body weight (bw) of metformin, and STZ-NA rats administered 500mg/kg bw of BGE (BGE). After 6weeks of administration, the homeostatic model assessment of insulin resistance (12%) in BGE decreased compared to DM. Strikingly, the fasting blood glucose (23%) and oral glucose tolerance test (15%) were improved in BGE compared to DM. BGE also increased insulin immunoreactivities in pancreatic β-cells. In sum, BGE exhibits anti-hyperglycemic effects by improving fasting glucose levels and insulin secretion from pancreatic β-cells in the STZ-NA-induced diabetic rats.

Inositol supplementation for the prevention and treatment of gestational diabetes mellitus: a meta-analysis of randomized controlled trials.

Inositol is a potential new therapeutic agent for gestational diabetes mellitus (GDM), but its effectiveness is still controversial. The aim of the report was to evaluate the effectiveness of inositol to preventing or reducing the severity of GDM. We searched PubMed, EmBase, Web of science, Cochrane library databases, Clinicaltrials.gov, and International Clinical Trials Registry Platform for randomized controlled trials (RCTs) assessing the effectiveness of inositol supplementation to prevent and treat GDM. This meta-analysis was performed using the random-effects model. A total of 7 RCTs (1319 pregnant women at high risk of GDM) were included in the meta-analysis. The meta-analysis found that inositol supplementation resulted in a significantly lower incidence of GDM in the inositol versus the control group (odds ratio [OR] 0.40; 95% confidence interval [CI] 0.24-0.67; P = 0.0005). The inositol group had improved fasting glucose oral glucose tolerance test (FG OGTT; mean difference [MD] = -3.20; 95% CI -4.45 to -1.95; P < 0.00001), 1-h OGTT (MD = -7.24; 95% CI -12.23 to -2.25; P = 0.004), and 2-h OGTT (MD = -7.15; 95% CI -12.86 to -1.44; P = 0.01) results. Inositol also reduced the risk of pregnancy-induced hypertension (OR 0.37; 95% CI 0.18-0.75; P = 0.006) and preterm birth (OR 0.35; 95% CI 0.18-0.69; P = 0.003). A meta-analysis of 4 RCTs including 320 GDM patients showed that the patients' insulin resistance (P < 0.05) and neonatal hypoglycemia risk (OR 0.10, 95% CI 0.01-0.88; P = 0.04) were lower in the inositol than in the control group. Inositol supplementation during pregnancy has the potential to prevent GDM, improve glycemic control, and reduce preterm birth rates.

Metabolic effects of monounsaturated fatty acid−enriched diets on glycaemic control in patient with type 2 diabetes: an evidence-based case report

Introduction: Diabetes mellitus type 2 (T2D) is the most common type of diabetes. There is an ongoing debate as to whether nutrient quality or quantity is mainly responsible for the effects on hyperglycaemic control of patients with T2D. Monounsaturated fatty acid (MUFA) has a metabolic effect in reducing the risk factor for metabolic syndrome to prevent and control hyperglycaemia in patients with T2D and is recommended by professional organizations.&#x0D; Methods: Literature searching was conducted by advanced searching in Pubmed, Cochrane Library, Scopus, and ProQuest database using MeSH Terms combined with Title/Abstract. After removing duplicates, the literature were screened based on the eligibility criteria. Critical appraisal and level of evidence of the selected literature were determined based on Oxford Centre for Evidence-Based Medicine.&#x0D; Results: Two selected literature were relevant to answer our clinical question, both literature are systematic review/meta-analysis studies. The first literature is a study by Fumiaki et al. (2016), while the second is by Frank Qian et al. (2016). All literature provided evidence that a diet high in MUFA could improve glucose-insulin homeostasis among patients with T2D. These effects were marked by lower fasting blood glucose and haemoglobin A1c (HbA1c), and insulin level in the enriched MUFA diet group compared to PUFA.&#x0D; Conclusion: Nutrient quality is mainly responsible for the effects on glycaemic control profile in patients with T2D, with a high MUFA diet consistent with favourable effects to improve fasting glucose and HbA1c.

Type 2 Diabetes mellitus alters the cargo of (poly)phenol metabolome and the oxidative status in circulating lipoproteins

The incidence of diabetes on the worldwide population has tripled in the past 5 decades. While drug-based therapies are valuable strategies to treat and ease the socio-economic burden of diabetes, nutritional strategies offer valuable alternatives to prevent and manage diabetes onset and contribute to the sustainability of health budgets. Whilst, intervention studies have shown that (poly)phenol-rich diets improve fasting glucose levels and other blood parameters, very little is known about the distribution of ingested polyphenols in circulation and the impact of diabetes on its cargo.In this study we investigate the impact of type 2 diabetes on the cargo of plasma (poly)phenols. Our results show that phenolic compounds are heterogeneously distributed in circulation though mainly transported by lipoprotein populations. We also found that diabetes has a marked effect on the phenolic content transported by VLDL resulting in the decrease in the content of flavonoids and consequently a decrease in the antioxidant capacity. In addition to the reduced bioavailability of (poly)phenol metabolites and increase of oxidative status in LDL and HDL populations in diabetes, cell-based assays show that sub-micromolar amounts of microbial (poly)phenol metabolites are able to counteract the pro-inflammatory status in glucose-challenged endothelial cells.Our findings highlight the relevance of triglyceride-rich lipoproteins in the transport and delivery of bioactive plant-based compounds to the endothelium in T2DM supporting the adoption of nutritional guidelines as an alternative strategy to drug-based therapeutic approaches.

Needle-free injection of basal insulin improves fasting glucose variability as assessed by continuous glucose monitoring in T2DM: a prospective randomized multicenter open-label crossover study

ABSTRACT Background Fasting glucose variability (FGV) extensively promotes the onset and development of diabetic complications. This study aimed to evaluate the FGV in type 2 diabetes mellitus (T2DM) patients administered basal insulin using a needle-free insulin injector (NFII). Research design and methods This was a prospective randomized multicenter open-label crossover study. We randomly assigned 48 T2DM patients to receive basal insulin by NFII or conventional insulin pen (CIP) for 7–14 days and were then crossed over after washout. We conducted continuous glucose monitoring to investigate the FGV, our primary outcome was a composite parameter of the FGV with a fasting blood glucose target between 4.4 and 6.1 mmol/L. Results The coefficient of variation for sensor glucose at 6 a.m. with CIP was 11.67 (8.70,14.81)% vs. 9.48 (6.48,12.24)% with NFII (p = 0.003), and the coefficient of variation for mean sensor glucose at 5–6 a.m. with CIP was 12.70 (9.17,16.56)% vs. 9.23 (7.01,11.98)% with NFII (p < 0.001). The overall basal insulin dosage with CIP injection was 18.00 (16.00, 20.00) IU vs. 16.00 (12.00, 19.00) IU during NFII (p < 0.003). Conclusion Compared with CIP, the use of the NFII to inject basal insulin improved FGV in T2DM. Clinical trial registration https://www.chictr.org.cn Identifier is ChiCTR2000034674.

In gestational diabetes, patient‐led insulin titration is rapidly effective, safe and is associated with reduced birthweight

AbstractBackground: Elevated fasting glucose in gestational diabetes (GDM) is the strongest predictor of adverse pregnancy outcomes but is difficult to treat. We assessed the effectiveness, safety, and patient acceptability of a simple patient‐led insulin dose titration algorithm in GDM, targeting rapid reduction in fasting glucose.Methods: Once initiated on basal insulin, women were asked to increase their dose by 4 units daily, following every fasting glucose ≥5.0mmol/L. We evaluated pregnancy outcomes, rates of hypoglycaemia and time taken to achieve target readings (&lt;5.3mmol/L) before and after this practice change. We undertook patient interviews and questionnaires to capture the patient perspective.Results: Insulin was commenced at a median 30+4 weeks with fasting glucose control (defined as the first of three consecutive readings &lt;5.3mmol/L) achieved after a median 4 days (IQR: 1–11) and maintained throughout pregnancy with further patient‐led titrations. Hypoglycaemia was uncommon; 1.7% of all fasting glucose readings were &lt;3.5mmol/L and 0.3% were &lt;3.0mmol/L. No patients experienced hypoglycaemia requiring assistance. At delivery, patient‐led titration achieved higher final insulin doses (53 vs 36 units/day; p=0.027), improved fasting glucose (4.6 vs 5.1mmol/L; p=0.031), and significantly lower birthweight (Z‐scores 0.34 vs 0.92; p=0.005) compared to our previous routine practice. Women liked the intervention and having increased responsibility for their own management.Conclusions: In GDM significant reduction in birthweight is achieved with patient‐led insulin dose titration. Following insulin initiation glycaemic control is achieved rapidly and maintained without detrimental hypoglycaemia. Copyright © 2022 John Wiley &amp; Sons.

830-P: The Pan-PPAR Agonist Lanifibranor Improves Nonalcoholic Steatohepatitis (NASH) and Glycemic Control

Lanifibranor therapy resulted in both NASH resolution and fibrosis reduction in the phase 2b NATIVE study in patients with non-cirrhotic NASH, compared to placebo. PPAR signaling is involved in common pathways of NASH and type 2 diabetes (T2D) . We evaluated the association between the effect of lanifibranor on glycemic control (GC) and NASH markers. Methods: NATIVE included 247 patients, randomized to lanifibranor 800, 1200 mg/d or placebo for 24 weeks of treatment; 228 patients completed the trial. Efficacy in NASH was measured with SAF score (primary endpoint) and NASH-CRN grading and fibrosis staging. Biomarkers for insulin resistance (IR) , GC, lipid metabolism, inflammation, liver enzymes and imaging of hepatic steatosis by continuous attenuation parameter (CAP) were analyzed at baseline (BL) and end of treatment (EOT) . Correlations between HbA1c (≤6, &amp;gt;6 - ≤7 and &amp;gt;7%) at BL and HbA1c change from BL to EOT with improvement in biomarkers and histologic features of NASH at EOT were assessed. Results: T2D was present in 103 (42%) patients. The composite endpoint of NASH resolution and fibrosis improvement in the overall and T2D group for lanifibranor (pooled data) versus (vs) placebo was 26% vs. 7% (p&amp;lt;0.001) , and 26% vs. 3% (p=0.003) , respectively. Irrespective of T2D status, lanifibranor improved fasting glucose (FG) , IR, lipid metabolism, C-reactive protein, and liver enzymes. In contrast to placebo, lanifibranor improved mean HbA1c from BL in the overall and T2D group, -0.41% and -0.66%, respectively. In the lanifibranor group, BL HbA1c correlated with BL NASH activity and fibrosis; HbA1c decrease at EOT correlated with improvement of FG, insulin, IR, liver enzymes, HDL-cholesterol, triglycerides, ApoB, ApoB/ApoA1, CAP and histologic improvement of steatosis and ballooning. Conclusion: GC correlates with NASH severity. The improvement of metabolic markers of NASH and hepatic steatosis with lanifibranor treatment is consistent with its beneficial effect on GC. Disclosure M.P.Cooreman: Employee; Inventiva Pharma. S.Francque: None. L.Dzen: Employee; Inventiva Pharma. P.Huot-marchand: Employee; Inventiva Pharma. J.L.Junien: None. P.Broqua: None. M.F.Abdelmalek: Advisory Panel; Akero Therapeutics, Inc., Bristol-Myers Squibb Company, Inventiva Pharma, Madrigal Pharmaceuticals, Inc., NGM Biopharmaceuticals, Novo Nordisk, Consultant; Hanmi Pharm. Co., Ltd., Research Support; Akero Therapeutics, Inc., Allergan, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Celgene, DURECT Corporation, Enanta, Enyo Pharma, Hanmi Pharm. Co., Ltd., Intercept Pharmaceuticals, Inc., Inventiva Pharma, Madrigal Pharmaceuticals, Inc., NGM Biopharmaceuticals, Novo Nordisk, Poxel SA, TARGET PharmaSolutions, Inc., Viking Therapeutics.

Alternations in markers of insulin resistance: HOMA-IR, HOMA-B, QUICKI, after dual therapy combination with telmisartan/amlodipine in prediabetic hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction-Purpose The combination of telmisartan and amlodipine in tablet form indicated for patients whose arterial blood pressure cannot be fully managed with monotreatment. The purpose of this study was to investigate the effect of the fixed combination telmisartan/amlodipine 80/5mg per day on arterial pressure levels and the variation of HOMA-IR, HOMA-B and QUICKI values in patients with stage 2 hypertension (systolic blood pressure (SBP) 160-179 mmHg and/or diastolic blood pressure (DBP) 100-109 mmHg) and with prediabetes (IFG/IGT) before and after the 3-month treatment with the administration of the fixed combination. Methods Data collected from 51 patients who have visited our outpatient clinic for lipid metabolism disorders during the period 2014-2018. 51 persons with BMI: 29.32 [27.37-31.65] (25 male, 16 female) had been randomized in the group for telmisartan/amlodipine 80/5mg per day. The median values for the study’s sample in SBP and DBP were: 163[158-168] and 100[95-106] mmHg, respectively. Their somatometric and demographic characteristics were recorded in the beginning of the study and are presented on Table 1Α. Results The results of the variations in SBP and DBP, as well as the variations in glucose, insulin, HOMA-IR, HOMA-B and QUICKI before and after the 3-month treatment are presented on Table 1B. Conclusions From the sampled patients it can be observed that the 3-month treatment with telmisartan/amlodipine statistically significantly improved (p=0.005) the HOMA-IR values while improving fasting glucose and insulin levels. Finally, there was a statistically significant reduction in QUICKI values and a statistically insignificant reduction in HOMA-B.

Phosphoproteomics reveals that camel and goat milk improve glucose homeostasis in HDF/STZ-induced diabetic rats through activation of hepatic AMPK and GSK3-GYS axis

Diabetes is a serious public health problem with global implications. Among many diabetes management therapies, non-pharmacological therapies such as those that focus on diet and exercise are gradually becoming more acceptable to patients. Within dietary management options, dairy products such as camel and goat milk are valued for their specific health benefits. The aim of this study was therefore to investigate the effect of camel and goat milk consumption on glucose homeostasis in high-fat diet and streptozotocin (HFD/STZ) induced diabetic rats. HFD/STZ-induced diabetic rats were fed with different milk for 35 days. Parameters related to glucose homeostasis, as well as hepatic proteome and phosphoproteome were investigated. The results of which showed that camel and goat milk consumption improved fasting glucose levels, glucose tolerance, and indicators related to lipid metabolism, while bovine and sheep milk consumption did not work. In addition, the hepatic phosphoproteome suggests that the ameliorative effect of both camel and goat milk was associated with the activation of AMPK. However, camel milk consumption further elevated the phosphorylation level of hepatic ACC, while goat milk consumption activated GSK3-GYS axis-related proteins. The present study investigated the possible mechanisms by which camel and goat milk consumption improves glucose homeostasis in HFD/STZ-induced diabetic rats and revealed their differences in the mechanism of antidiabetic effect.

Long-Term Diabetes Improvement After Duodenal Exclusion in Zucker Diabetic Fatty Rats Is Associated with Prevention of Strain-Specific Pancreatic Remodeling and Increased Beta Cell Proliferation.

BackgroundResponse to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas.Materials and MethodsWe performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness.ResultsDJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham.ConclusionIn this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis.Graphical abstract

Randomized controlled trial for time-restricted eating in healthy volunteers without obesity

Time-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406.

Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers.

IntroductionFasting glucose increases with age and is linked to modifiable Alzheimer's disease risk factors such as cardiovascular disease and Type 2 diabetes (T2D).MethodsWe leveraged available biospecimens and neuroimaging measures collected during the Alzheimer's Prevention Through Exercise (APEx) trial (n = 105) to examine the longitudinal relationship between change in blood glucose metabolism and change in regional cerebral amyloid deposition and gray and white matter (WM) neurodegeneration in older adults over 1 year of follow‐up.ResultsIndividuals with improving fasting glucose (n = 61) exhibited less atrophy and regional amyloid accumulation compared to those whose fasting glucose worsened over 1 year (n = 44). Specifically, while individuals with increasing fasting glucose did not yet show cognitive decline, they did have regional atrophy in the hippocampus and inferior parietal cortex, and increased amyloid accumulation in the precuneus cortex. Signs of early dementia pathology occurred in the absence of significant group differences in insulin or body composition, and was not modified by apolipoprotein E ε4 carrier status.DiscussionDysregulation of glucose in late life may signal preclinical brain change prior to clinically relevant cognitive decline. Additional work is needed to determine whether treatments specifically targeting fasting glucose levels may impact change in brain structure or cerebral amyloid in older adults.