Reduced Fasting Plasma Glucose Levels Research Articles

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people

BackgroundEpidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. MethodsThe study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. ResultsIn multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (β = − 0.016, 95 % CI: − 0.030 to − 0.003 for V; β = − 0.021, 95 % CI: − 0.033 to − 0.009 for Mg), and urine Se was positively related to the FPG levels (β = 0.024, 95 % CI: 0.014–0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. ConclusionsBoth Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was −1.02% (−1.11, −0.93) in the dorzagliatin group and −0.36% (−0.45, −0.26) in the placebo group (estimated treatment difference, −0.66%; 95% CI: −0.79, −0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile (NCT03141073).

Comparison of Efficacy of Glimepiride, Alogliptin, and Alogliptin-Pioglitazone as the Initial Periods of Therapy in Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Multicenter, Randomized, Controlled Study.

BackgroundThe choice of an optimal oral hypoglycemic agent in the initial treatment periods for type 2 diabetes mellitus (T2DM) patients remains difficult and deliberate. We compared the efficacy and safety of glimepiride (GLIM), alogliptin (ALO), and alogliptin-pioglitazone (ALO-PIO) in poorly controlled T2DM patients with drug-naïve or metformin failure.MethodsIn this three-arm, multicenter, open-label, randomized, controlled trial, poorly controlled T2DM patients were randomized to receive GLIM (n=35), ALO (n=31), or ALO-PIO (n=33) therapy for 24 weeks. The primary endpoint was change in the mean glycosylated hemoglobin (HbA1c) levels at week 24 from baseline. Secondary endpoints were changes in HbA1c level at week 12 from baseline, fasting plasma glucose (FPG) levels, lipid profiles at weeks 12 and 24, and parameters of glycemic variability, assessed by continuous glucose monitoring for 24 weeks.ResultsAt weeks 12 and 24, the ALO-PIO group showed significant reduction in HbA1c levels compared to the ALO group (–0.96%±0.17% vs. –0.37%±0.17% at week 12; –1.13%±0.19% vs. –0.18%±0.2% at week 24). The ALO-PIO therapy caused greater reduction in FPG levels and significant increase in high-density lipoprotein cholesterol levels at weeks 12 and 24 than the ALO therapy. Compared to low-dose GLIM therapy, ALO-PIO therapy showed greater improvement in glycemic variability. The adverse events were similar among the three arms.ConclusionALO-PIO combination therapy during the early period exerts better glycemic control than ALO monotherapy and excellency in glycemic variability than low-dose sulfonylurea therapy in uncontrolled, drug-naïve or metformin failed T2DM patients.

Tangnaikang Alleviates Hyperglycemia and Improves Gut Microbiota in Diabetic Mice.

Dysregulation of gut microbiota contributes to the development of type 2 diabetes. To investigate the antidiabetic effect of Tangnaikang and its regulation of gut microbiota in diabetic KKAy mice, a type 2 diabetes mouse model was established by feeding KKAy mice with a high-fat diet (HFD) for 2 weeks. The diabetic KKAy mice were treated with vehicle, Acarbose, or different doses of Tangnaikang once a day for 8 weeks. The fasting plasma glucose (FPG) levels and bodyweights were measured weekly. The fecal and blood samples were collected 8 weeks after treatment. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore the effects of Tangnaikang treatment on the richness, diversity, and relative abundance of gut microbiota. Compared with other treatments, high-dose Tangnaikang (4.68 g/kg) significantly reduced FPG levels while elevating bodyweights in model mice. Compared with saline treatment, different doses of Tangnaikang significantly increased gut microbial species richness and diversity. Linear discriminant analysis effect size identified potential bacterial biomarkers associated with Tangnaikang treatment. Relative abundance analysis revealed that Tangnaikang treatment modulated the abundance of gut bacteria at the class and genus levels, such as Bacilli, Lactobacillus, and Alistipes. The principal component analysis demonstrated that, compared with the samples of the high-dose group, the samples of medium-dose and low-dose groups were closer to those of the model group. Tangnaikang alleviated hyperglycemia and improved the composition and abundance of gut microbiota in diabetic KKAy mice.

Xiaoke Decoction in treatment of type II diabetes: A Meta-analysis

ObjectiveTo systematically evaluate the clinical effect of Xiaoke Decoction in the treatment of type 2 diabetes. MethodsChinese databases such as CNKI, Wanfang, Weipu Chinese Biomedical Journal Database, and Chinese Medical Biological Literature Database, PubMed, Cochrane Library, Embase, and Web of Science were searched for English language literature from their inception until November 2019. A Meta-analysis was performed using RevMan 5.3 and Stata 12.0. ResultsThirty-eight studies were included in this study, with a total of 3757 patients. It was found that adding Xiaoke Decoction could improve total efficiency. The Xiaoke Decoction groups surpassed the western medicine groups regarding improvement in total efficiency (OR = 3.49; 95% CI: 2.78–4.39, P < 0.00001). Adding Xiaoke Decoction could lower the fasting plasma glucose (FPG) level. The Xiaoke Decoction groups surpassed the western medicine groups regarding reduction in FPG levels (MD = −1.14; 95% CI: −1.36 to 0.92, P < 0.00001). Adding Xiaoke Decoction could lower the 2 h postprandial blood glucose (2hPG) level. The Xiaoke Decoction groups surpassed the western medicine groups regarding reduction in 2hPG (MD = −1.40; 95% CI: −1.61 to 1.19, P < 0.00001). Adding Xiaoke Decoction could lower glycated hemoglobin (HbA1c). The Xiaoke Decoction groups surpassed the western medicine groups regarding reduction in HbA1c (MD = −0.77; 95% CI: −0.95 to 0.58, P < 0.00001). It was found that adding Xiaoke Decoction could lower the traditional Chinese medicine (TCM) syndrome score. The TCM syndrome scores among patients in the Xiaoke Decoction group were lower than those among patients in the control group after treatment (MD = −4.90; 95% CI: −7.22 to 2.57, P < 0.0001). At the same time, we conducted a subgroup and sensitivity analysis of age and intervention duration on the heterogeneity of total efficiency, FPG, 2hPG, HbAlc, and TCM syndrome score outcome indicators. For detecting publication bias, an egger test was conducted. ConclusionCompared with western medicine alone, Xiaoke Decoction has more advantages for the treatment of type 2 diabetes with respect to total efficiency, FPG, 2hPG, HbAlc, and TCM syndrome score.

Total polyphenols and antihyperglycemic activity of aqueous fruits extract of Abelmoschus esculentus: Modeling and optimization of extraction conditions.

Aqueous fruits extract of Abelmoschus esculentus (L.) Moench (Malvaceae) has been used traditionally in several communities to alleviate elevated blood glucose levels. However, optimized extraction conditions have not been reported. Thus, this study determined the optimal extraction conditions for extracting polyphenols from A. esculentus fruits and evaluated antihyperglycemic activity in vivo. Extraction time, temperature, and solid-to-solvent ratio were optimized using Response Surface Methodology (RSM). Total polyphenols and flavonoids were quantified using the Folin-Ciocalteu and aluminium chloride colorimetric methods, respectively. The fingerprint and quantification of quercetin—a major flavonoid with an antihyperglycemic effect was done using the chromatographic method. The antihyperglycemic activity was determined in a high-fat diet-Streptozotocin rat model. The rats were assigned to five groups (n = 6): Group 1 and 2 were normal and diabetic control received distilled water 1 mL/100g; Treatment group 3 and 4 received standardized A. esculentus fruit extract (AEFE) at a dose of 100 and 200 mg/kg, respectively; Group 5 received 5 mg/kg glibenclamide. All treatments were given orally for 14 days. Measurements of fasting plasma glucose (FPG) and body weight were done weekly. The RSM quadratic model predicted total polyphenols of 22.16 mg GAE/g DW. At optimal conditions of a solid-to-solvent ratio of 5%, extraction time 1 h, and extraction temperature of 70°C, confirmation experiments yield 20.2 [95% CI; 16.7 to 27.6] mg GAE/g DW, implying the model successfully predicted total polyphenols. The extract HPLC fingerprint showed 13 characteristic peaks with 0.45 ± 0.02 μg/g DW of quercetin. Compared with diabetic control, the standardized AEFE reduced FPG level dose-dependently (P < 0.001) with an EC50 of 141.4 mg/kg. Together, at optimal extraction conditions, extract with a high content of total polyphenols and good antihyperglycemic activity can be obtained. Studies are needed to identify additional polyphenolic compounds and determine their antidiabetic effects.

Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review.

Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

Role of vitamin D‐calcium supplementation on metabolic profile and oxidative stress in gestational diabetes mellitus: A randomized controlled trial

To assess role of vitamin D-calcium supplementation on the metabolic profile and oxidative stress in women with Gestational Diabetes Mellitus (GDM) controlled on diet. A randomized controlled trial was conducted at a tertiary care teaching hospital. Seventy women diagnosed as GDM at 24-28 weeks of gestation, controlled on a diabetic diet, were randomized to receive either vitamin D 1000 IU and calcium 1000 mg (group A, n = 34) or vitamin D 250 IU and calcium 500 mg (group B, n = 36) daily for 6 weeks. Levels of serum 25-hydroxy vitamin D, fasting plasma glucose (FPG), serum insulin, fasting lipid profile and total glutathione (GSH) were analyzed both prior to and after supplementation. Means, standard deviations and mean change were computed. Paired and independent t-tests were used to determine statistical significance between the two groups. Women in group A showed a significant reduction in FPG level (P-value = 0.007), fasting serum insulin level (P-value = 0.000), LDL (P-value = 0.000), total cholesterol levels (P-value = 0.000) and increase in HDL levels (P-value = 0.000). Group B had a significant fall only in FPG after 6 weeks supplementation. A significant change in total glutathione level (P-value = 0.000) was observed in both groups. Vitamin D and calcium supplementation at a dose of 1000 IU and 1000 mg, respectively, has a beneficial role in glucose metabolism, lipid metabolism and oxidative stress in GDM.

Effects of Anthocyanin Extracts from Bilberry (Vaccinium myrtillus L.) and Purple Potato (Solanum tuberosum L. var. 'Synkeä Sakari') on the Plasma Metabolomic Profile of Zucker Diabetic Fatty Rats.

This study compared the effects of the nonacylated and acylated anthocyanin-rich extracts on plasma metabolic profiles of Zucker diabetic fatty rats. The rats were fed with the nonacylated anthocyanin extract from bilberries (NAAB) or the acylated anthocyanin extract from purple potatoes (AAPP) at daily doses of 25 and 50 mg/kg body weight for 8 weeks. 1H NMR metabolomics was used to study the changes in plasma metabolites. A reduced fasting plasma glucose level was seen in all anthocyanin-fed groups, especially in the groups fed with NAAB. Both NAAB and AAPP decreased the levels of branched-chain amino acids and improved lipid profiles. AAPP increased the glutamine/glutamate ratio and decreased the levels of glycerol and metabolites involved in glycolysis, suggesting improved insulin sensitivity, gluconeogenesis, and glycolysis. AAPP decreased the hepatic TBC1D1 and G6PC messenger RNA level, suggesting regulation of gluconeogenesis and lipogenesis. This study indicated that AAPP and NAAB affected the plasma metabolic profile of diabetic rats differently.

The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis.

To evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM) or obese adults. A meta-analysis was conducted of trials by searching in PubMed, Embase, CENTRAL, Web of Science, and Scopus. A total of five randomized controlled trials (RCTs) and six nonrandomized controlled trials (NCTs) enrolled 1604 participants were identified for meta-analysis. Compared with control/placebo, the combination therapy group had significantly reduced fasting plasma glucose level and 2 h postprandial glucose by 1.28 mmol/L (95% confidence interval [CI]: -1.39, -1.16; p < 0.001) and 1.34 mmol/L (95% CI: -1.47, -1.21; p < 0.001); glycosylated hemoglobin (HbA1c) by 1.32% (95% CI: -1.43, -1.20; p < 0.001); body weight by 0.93 kg (95% CI: -1.04, -0.83; p < 0.001), and systolic blood pressure (SBP) by 1.05 mmHg (95% CI: -1.17, -0.93; p < 0.001). The incidence of genital mycotic infections and urinary infections did not significantly differ from those in the control group, with relative risks (RRs) of 1.67 (95% CI: 0.85, 3.27; p = 0.651) and 1.25 (95% CI: 0.73, 2.15; p = 0.905), respectively. A decreased incidence of cardiovascular events was seen in the combination therapy group (RR = 0.19; 95% CI: 0.04, 0.96; p = 0.403), while an incidence of hypoglycemia was reported (RR = 2.22; 95% CI: 1.20, 4.10; p = 0.71). SGLT2 inhibitors and GLP-1 agonists combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total adverse events or genital and urinary infections in patients with T2DM or obesity.

Evaluation of type 2 diabetes treatment with gliclazide modified release in Azerbaijan (the EdiAzer study): Results from a 16-week observational clinical study

Introduction: Type 2 diabetes is a major public health problem across all economic regions. This open-label study collected real-world data on patients presenting with type 2 diabetes in Azerbaijan treated with gliclazide modified release (MR). Materials and Methods: Newly-diagnosed patients uncontrolled by diet, and patients uncontrolled by metformin were prescribed gliclazide MR 60mg (30–120mg/day) for 16 weeks. Primary study endpoints were changes in mean glycated hemoglobin A1c (HbA1c) and percentage of participants achieving HbA1c ≤7.0% and/or an HbA1c improvement ≥1.0%. Secondary endpoints included changes in mean fasting plasma glucose (FPG) and weight. Serious adverse events were monitored throughout the study. Results: Data from 105 patients were available for analysis. Mean age was 55.1 ± 10.4 years, 53.3% were female and 82.9% were overweight or obese. Mean duration of diabetes was 2.3 ± 2.6 years. A total of 44 patients were receiving metformin before study entry. At W0, 61 patients (58.1%) were prescribed gliclazide MR monotherapy, and 44 (41.9%) were prescribed gliclazide MR in combination with the metformin. At the end of the study, a statistically significant decrease was observed in mean HbA1c levels from 8.8% ± 1.4% to 7.6% ± 1.0% (P < 0.001). In addition, 30 (28.6%) patients achieved an HbA1c <7.0% (P < 0.0001), and 61 (58.1%) an HbA1c reduction of ≥1.0%. Reductions in FPG levels were statistically significant compared with baseline from week 2 onward. No weight gain was observed, and there were no serious adverse events, including no reports of severe hypoglycemia. Conclusion: Gliclazide MR is an effective and well-tolerated first- or second-line agent in type 2 diabetes and may be particularly valuable in low-to-middle income countries where therapeutic options are limited by accessibility and cost.

Effect of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on gluconeogenesis in proximal renal tubules.

To investigate the effect of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on renal gluconeogenesis in vitro, ex vivo and in vivo. We treated HK-2 cells (human renal proximal tubule cells) and mouse primary renal proximal tubule cells with dapagliflozin, and evaluated the process of renal gluconeogenesis. We also examined the effect of dapagliflozin on renal gluconeogenesis in normoglycaemic and hyperglycaemic mice. Dapagliflozin enhanced renal gluconeogenesis in vitro, ex vivo and in vivo. It increased phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), peroxisome proliferative activated receptor-gamma co-activator 1α (PGC-1α) and phosphorylated cyclic-AMP response element binding protein (CREB) expression and decreased phosphorylated Forkhead Box O1 (FOXO1) expression in HK-2 cells, mouse primary renal proximal tubule cells, and the mouse renal cortex. Glutamine enhanced the gluconeogenic effect of dapagliflozin in HK-2 cells. Also, dapagliflozin increased 14 C-glutamine utilization in HK-2 cells. Glucagon did not affect dapagliflozin-induced enhancement in renal gluconeogenesis in HK-2 cells. SGLT2 gene knockdown with siRNA resulted in an increase of gluconeogenic gene expression and associated transcription factors in HK-2 cells. Dapagliflozin reduced fasting plasma glucose levels and improved oral glucose tolerance and insulin tolerance in high-fat diet-fed hyperglycaemic mice, although renal gluconeogenesis was enhanced. Dapagliflozin increased levels of gluconeogenic enzyme in the renal cortex and consequently increased renal gluconeogenesis, which is mediated by SGLT2 inhibition.

2300-PUB: The Efficacy and Safety of Combinations of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes: A Systematic Review and Meta-analysis

Objective: The aim of this study was to evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). Methods: We searched clinical trials indexed in PubMed, Embase, CENTRAL, Web of Science, and Scopus from inception through December 3, 2018. A meta-analysis was conducted of trials involving patients receiving SGLT2 inhibitors and GLP-1 agonists using Stata 12.0 software. Results: A total of 9 clinical trials, including 5 randomized controlled trials (RCTs), that enrolled 1369 participants were identified for meta-analysis. Compared with the control/placebo group, the combination therapy group had significantly reduced fasting plasma glucose level by 0.78 mmol/L (95% confidence interval [CI]: -1.36, -0.2), 2-h postprandial glucose level by 0.47mmol/L (95% CI: -0.69, -0.24), glycosylated hemoglobin (HbA1c) by 0.73% (95% CI: -1.45, 0); body weight that was lower by 0.39 kg (95% CI: -0.59, -0.18) (4 non-randomized controlled trials indicated a larger reduction in body weight of 3.53 kg), and systolic blood pressure (SBP) that was lower by 0.26 mmHg (95% CI: -0.40, -0.11). The total incidence of adverse events (AEs) and genital and urinary infections in the therapy group did not significantly differ from those in the control group, with relative risks (RRs) of 1.06 (95% CI: 0.96, 1.17) and 1.19 (95% CI: 0.69, 2.07), respectively. An increased incidence of hypoglycemia was seen in the combination therapy group (RR=2.49; 95% CI: 1.40, 4.45). Conclusions: SGLT2 inhibitor and GLP-1 agonist combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total AEs or genital and urinary infections in patients with T2DM. However, the risk of hypoglycemia should be carefully monitored in future clinical trials. Disclosure M. Guo: None. J. Gu: None. J. Li: None. Y. Xu: None. Funding National Natural Science Foundation of China (81800741)

Effects of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis of randomized controlled trials was performed to determine the effect of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until August 30, 2018. Nine studies with 10 effect sizes out of 357 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that quercetin supplementation did not affect fasting plasma glucose (FPG), homeostasis model of assessment-estimated insulin resistance, and hemoglobin A1c levels. In subgroup analysis, quercetin supplementation significantly reduced FPG in studies with a duration of ≥8weeks (weighted mean difference [WMD]: -0.94; 95% confidence interval [CI; -1.81, -0.07]) and used quercetin in dosages of ≥500mg/day (WMD: -1.08; 95% CI [-2.08, -0.07]). In addition, subgroup analysis revealed a significant reduction in insulin concentrations following supplementation with quercetin in studies that enrolled individuals aged <45years (WMD: -1.36; 95% CI [-1.76, -0.97]) and that used quercetin in dosages of ≥500mg/day (WMD: -1.57; 95% CI [-1.98, -1.16]). In summary, subgroup analysis based on duration of ≥8weeks and used quercetin in dosages of ≥500mg/day significantly reduced FPG levels.

EFFECT OF SUPPLEMENTATION OF WITHANIA COAGULANS FRUIT ON THE FASTING PLASMA GLUCOSE LEVELS OF TYPE 2 DIABETIC SUBJECTS

Objective: The objective of this study is to determine the effect of supplementation of Withania coagulans fruit on the fasting plasma glucose (FPG) levels of type 2 diabetic subjects.Methods: In the natural system of medicine, many plants have been claimed to be useful for the management of diabetes mellitus. W. coagulans (Paneer poo) is one such source in which the fruit of the plant possesses hypoglycemic properties. The study was designed to determine the effect of a 60-day supplementation of W. coagulans fruit drink on the FPG levels of Type 2 diabetic subjects. W. coagulans fruit (6 numbers - approximately 2.5 g) was soaked overnight in 100 ml of water. This was administered to the experimental group. The control group received a placebo.Results: There was a significant decrease in the FPG levels of the experimental group on the 61st day. There was a statistically significant increase in the FPG level of the control group on the 61st day, showing that the placebo did not have any hypoglycemic effect.Conclusion: A significant reduction in FPG levels in the experimental group at the end of the study period proves that W. coagulans is a good hypoglycemic agent.

PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients.

AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.

Influence of Time of Yoga Practice and Gender Differences on Blood Glucose Levels in Type 2 Diabetes Mellitus and Normal Healthy Adults

Prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Many studies have demonstrated the effectiveness of yoga in improving glycaemic control, whereas no studies are available showing the impact of time of practice on glucose levels. The current study explores the effect of time of yoga practice on glucose levels in community-dwelling adults with and without T2DM. A total of 189 subjects with T2DM and 121 subjects without T2DM underwent a 10-day yoga program which includes practical and theory lecture sessions for 60min every day, either in the morning or evening. Baseline and post-intervention assessments of fasting plasma glucose (FPG) were measured on day-1 and day-10, respectively. Data analysis were done using Statistical Package for the Social Sciences (SPSS), version 16. Results of the study showed that in individuals with T2DM, a significantly higher reduction in FPG was observed while practicing yoga in the evening sessions than in the morning sessions. Likewise, a significant reduction in FPG was observed only in women who practiced yoga in the evening than in the morning, in non-diabetic healthy individuals, while the reduction was not statistically significant in men. Results of this study suggest that reduction in FPG level was better while practicing yoga in evening than morning. Similarly, women had a better reduction in blood glucose level than men.

Efficacy and Safety of Teneligliptin in Indian Patients with Inadequately Controlled Type 2 Diabetes Mellitus: A Randomized, Double-blind Study.

Aims:This study evaluated the efficacy and safety of teneligliptin in patients with inadequately controlled type 2 diabetes mellitus (T2DM).Settings and Design:This was a randomized, doubleblind, placebocontrolled, parallelgroup, multicenter, Phase III study.Subjects and Methods:Patients with T2DM and inadequate glycemic control (glycosylated hemoglobin [HbA1c]: >7.0-≤8.5%) were enrolled. Patients were randomly assigned (ratio: 2:1) to receive teneligliptin 20 mg (Glenmark) or placebo. The primary efficacy variable was change from baseline in HbA1c at week 16. Additional analyses included the proportion of patients who achieved target of HbA1c ≤7.0%, changes in fasting plasma glucose (FPG), and postprandial glucose (PPG).Statistical Analysis:Mean change in HbA1c was analyzed using an analysis of covariance model, least square (LS) means, 95% confidence intervals (CIs), and P values were calculated.Results:Overall, 237 patients were included. Patients of the teneligliptin group showed reduced HbA1c levels (LS mean difference = −0.304% for intent-to-treat [ITT]; −0.291% for per-protocol (PP) populations) after 16 weeks of treatment, and a statistically significant difference was observed between the ITT (LS mean difference = 0.555; 95% CI: 0.176–0.934; P = 0.0043) and PP populations (LS mean difference = 0.642; 95% CI: 0.233–1.052; P = 0.0023). Target HbA1c level was achieved by a greater proportion of teneligliptin group patients (ITT, 43.4%; PP, 43.6%) than placebo group patients (ITT, 27.3%; PP, 26.6%). Reduction in FPG levels was observed in ITT (LS mean difference: 8.829; 95% CI: −4.357–22.016; P = 0.1883) and PP populations (LS mean difference: 11.710 mg/dL; 95% CI: −2.893-26.312; P = 0.1154). Reduction in PPG levels was higher in teneligliptin group than placebo group in both ITT (LS mean difference = 25.849 mg/dL; 95% CI: 7.143–44.556; P = 0.0070) and PP populations (LS mean difference = 25.683 mg/dL; 95% CI: 5.830–45.536; P = 0.0115). Overall, 44 patients (18.6%) experienced at least one adverse event. Three or more hypoglycemic events were experienced by 2.5% patients of teneligliptin group and none in placebo group.Conclusion:Treatment with once-daily teneligliptin led to statistically significant and clinically meaningful reductions in HbA1c and PPG, and was well tolerated in Indian patients with T2DM.

Anti-diabetic effects of mulberry (Morus alba L.) branches and oxyresveratrol in streptozotocin-induced diabetic mice.

Despite with accumulating evidences on the anti-diabetic effects of mulberry branch (MB), the major active component for the activity has not been known. Oral administration of MB ethanol (EtOH) extracts [0.5 or 1g/kg body weight (BW)] once a day for 22days to streptozotocin-induced diabetic ICR mouse significantly reduced fasting blood and plasma glucose level in a dose dependent manner compared to those of the diabetic control. Administration of oxyresveratrol [ORT, 0.6g/kg BW], a major compound of MB EtOH extracts, to diabetic ICR mouse also significantly reduced fasting plasma glucose level. Further, ORT increased hepatic glucose transporter 2 transcription and glycogen content. Plasma insulin concentration and intestinal disaccharidase activity were not different between diabetic control and ORT groups. This suggests that ORT reduced plasma glucose by stimulating hepatic glucose uptake and glycogen storage. MB EtOH extracts and ORT could be potential adjunct therapies for diabetes management.

ANTI-DIABETIC AND ANTIOXIDANT POTENTIALS OF AQUEOUS EXTRACT OF EUCALYPTUS GLOBULUS IN EXPERIMENTALLY-INDUCED DIABETIC RATS

Background: Evaluation of the medicinal uses of plants remains a growing field of research. This study investigated&#x0D; the effects of Eucalyptus globules on alloxan -induced diabetic rats.&#x0D; Materials and Methods: Thirty male albino rats were randomized into 5 groups (n=6). Group A served as the control&#x0D; and was maintained on standard rat chow and water ad’libitum. Diabetes was induced in Group C, D and E animals by&#x0D; intraperitoneal administration of alloxan monohydrate (150 mg/kg). Groups B and D were orally administered with&#x0D; aqueous extract of Eucalyptus globulus at a dose of 150 mg/kg per oral daily for 4 weeks, while group E received&#x0D; glibenclamide at a dose of 0.6 mg/kg orally in addition. Fasting plasma glucose, antioxidant status (catalase and&#x0D; xanthine), malondialdehyde (MDA), liver function enzymes (AST and ALT) and bicarbonate ion (HC03&#x0D; -) were&#x0D; assessed after 4 weeks.&#x0D; Results: Aqueous extract of Eucalyptus globulus leaves significantly reduced fasting plasma glucose level, MDA,&#x0D; HC03&#x0D; -, and liver enzymes (P