Changes In Plasma Glucose Research Articles

Real-world evidence on the use of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) in people with suboptimally controlled type 2 diabetes in Romania: a prospective cohort study (STAR.Ro)

ObjectivesTo assess the effectiveness and safety of insulin glargine and lixisenatide (iGlarLixi) fixed-ratio combination on a cohort of Romanian adults with type 2 diabetes (T2D).DesignOpen-label, 24-week, prospective cohort study.Setting65 secondary...

Protective Effect and Possible Mechanisms of Artemisinin and Its Derivatives for Diabetic Nephropathy: A Systematic Review and Meta-Analysis in Animal Models.

Background Artemisinin and its derivatives have potential antidiabetic effects. There is no evaluation of reported studies in the literature on the treatment of diabetic nephropathy (DN), one of the commonest diabetic microangiopathies, with artemisinins. Here, we aimed to evaluate preclinical evidence for the efficacy and possible mechanisms of artemisinins in reducing diabetic renal injury. Methods We conducted an electronic literature search in fourteen databases from their inception to November 2021. All animal studies assessing the efficacy and safety of artemisinins in DN were included, regardless of publication or language. Overall, 178 articles were screened according to predefined inclusion and exclusion criteria. Finally, 18 eligible articles were included in this systematic review. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool was used to assess the risk of bias in the included studies. The primary outcomes were kidney function, proteinuria, and renal pathology. Secondary endpoints included changes in fasting plasma glucose (FPG) levels, body weight, and relevant mechanisms. Results Of the 18 included articles involving 418 animal models of DN, 1, 2, 6, and 9 used dihydroartemisinin, artemether, artesunate, and artemisinin, respectively. Overall, artemisinins reduced indicators of renal function, including blood urea nitrogen (P < 0.00001), serum creatinine (P < 0.00001), and kidney index (P = 0.0001) compared with control group treatment. Measurements of proteinuria (P < 0.00001), microalbuminuria (P < 0.05), and protein excretion (P = 0.0002) suggested that treatment with artemisinins reduced protein loss in animals with DN. Artemisinins may lower blood glucose levels (P = 0.01), but there is a risk of weight gain (P < 0.00001). Possible mechanisms of action of artemisinins include delaying renal fibrosis, reducing oxidative stress, and exerting antiapoptotic and anti-inflammatory effects. Conclusion Available evidence suggests that artemisinins may be protective against renal injury secondary to diabetes in preclinical studies; however, high-quality and long-term trials are needed to reliably determine the balance of benefits and harms.

Glucose Trajectory: More than Changing Glucose Tolerance with Age?

While glucose tolerance is widely known to deteriorate with age, there are individuals whose borderline elevated glucose does not presage development of diabetes, but there are people who do develop overt diabetes. In addition, elevated glucose may also presage other morbidities, particularly for those who show progressive deterioration in glucose control over time. This concept of the glucose trajectory has taken on recent significance with sophisticated mathematical modeling that can identify several different arcs, primarily based on longitudinal changes in fasting plasma glucose. Other trajectories, calculated on changes in glycated hemoglobin, or integrated responses to oral glucose tolerance tests, are less well characterized. The author has reviewed the literature in an attempt to clarify these different themes of age-related deterioration in glucose control, highlight conflicting definitions of glucose trajectory, and potentially identify avenues of further investigation. Genetic contributions to the risk of development of type 2 diabetes, artificial intelligence and mathematical models of diabetes risk, and the discrepancy between fasting glucose and postprandial measures, including glycated hemoglobin, in risk prediction are also considered.

IDF21-0679 INTENSIFY: effectiveness of insulin degludec/liraglutide (IDegLira) in a real-world T2DM population in the UAE

Background: In patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, combining a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin (BI) offers an effective treatment-intensification strategy. A fixed-ratio combination of insulin degludec and liraglutide (IDegLira; Novo Nordisk) was launched in the United Arab Emirates (UAE) in 2018. Aim: To investigate the effect of IDegLira in a real-world population of patients with T2DM switching from BI or GLP-1 RA (± oral antidiabetic drugs [OADs]) in routine clinical practice in the UAE. Method: INTENSIFY was a 26–38-week, multicentre, prospective, non-interventional, real-world study. T2DM patients (≥18 years) with inadequate glycaemic control on BI or GLP-1 RA (± OADs) were eligible if a switch to IDegLira had been planned. The primary endpoint was change in laboratory measured HbA1c from baseline to end of the study. Secondary endpoints included overall change in fasting plasma glucose (FPG); change in body weight; incidence of hypoglycaemic episodes in the 4-week (non-severe and nocturnal non-severe episodes) and 26-week (severe episodes) periods before end of study (EOS) versus before initiation of IDegLira treatment. Treatment preference and safety were also assessed. ClinicalTrials.gov identifier: NCT03823339 Results: Among 263 patients, 206 (78.3%) and 57 (21.7%) patients had previously received BI ± OADs and GLP-1 RA ± OADs, respectively. Baseline mean HbA1c was 9.29%. Switching to IDegLira was associated with a significant overall reduction in HbA1c, with an estimated mean (SE) change from baseline of –0.9% (0.1%), 95% CI, –1.1 to –0.7 (p<0.0001). There was also a significant reduction in FPG: overall mean (SE) change from baseline was –48.2 (5.9) mg/dL, 95% CI, –59.9 to –36.5 (p<0.0001). A significant reduction in body weight was achieved among patients previously treated with BI ± OADs,with an estimated mean (SE) change from baseline of –1.1 (0.2) kg, 95% CI, –1.5 to –0.6 (p<0.0001). The estimated incidence of hypoglycaemic episodes was numerically lower in the periods before EOS versus before initiation of IDegLira treatment (2 vs. 13, 2 vs. 6, and 2 vs. 4 episodes for non-severe, nocturnal non-severe, and severe hypoglycaemia, respectively). Overall, the number of IDegLira dose steps increased significantly (mean [SE] change, 6.1 [0.6] steps, 95% CI, 5.0–7.2 [p<0.0001]). Most patients (86%) preferred IDegLira over previous treatments. IDegLira was well tolerated with no unexpected safety findings. Discussion: Switching from BI or GLP-1 RA (± OADs) to IDegLira significantly improved glycaemic control in adults with T2DM. There were significant overall reductions in HbA1c and FPG; a significant reduction in body weight among patients previously on BI ± OADs, and a reduction in hypoglycaemic events. Conservative dose titration (an increase of approximately 1 dose step per month) was identified in the INTENSIFY study. A stricter titration schedule and frequent interaction between patients and investigators may have led to greater improvement in both primary and secondary endpoints.

Antioxidant for treatment of diabetic complications: A meta-analysis and systematic review.

Antioxidants may provide a complementary treatment for patients with chronic diseases. Nevertheless, studies that have measured the effects of antioxidant on diabetes complications have provided conflicting results. This study aimed to elucidate the association between antioxidant and diabetic complications and to develop robust evidence for clinical decisions by systematic reviews and meta-analysis. PubMed, Embase, The Cochrane Library, Web of Science, Scopus databases were searched to collect clinical studies related to the efficacy of antioxidants in the treatment of diabetes complications from inception to May 5, 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The data of diabetic nephropathy (DN), diabetic nonalcoholic fatty liver disease (NAFLD), and diabetic periodontitis were collected to analyze the effect of antioxidant on diabetes and the above three complications. The meta-analysis results showed that antioxidant treatment was associated with significantly changes in the fasting plasma glucose (FPG) (standardized mean difference [SMD]: - 0.21 [95% confidence interval [CI]: - 0.33, -0.10], p < 0.001), hemoglobin A1c (HbA1c) (MD: - 0.41 [95% CI: - 0.63, -0.18], p < 0.001), total antioxidant capacity (TAC) (SMD: 0.44 [95% CI: 0.24, 0.63], p < 0.001) and malondialdehyde (MDA) (SMD: - 0.82 [95% CI: - 1.24, -0.41], p < 0.001) than the control group. Antioxidant supplements have the potential to treat three complications of diabetes. In conclusion, the meta-analysis results indicate that antioxidant treatment is effective clinically for diabetes mellitus and its complications.

Serum Leptin, Plasma Glucose, and Lactate Changes following Aerobic Exhaustive Incremental Exercise in Trained 18-26 Years Old Men

Serum Leptin, Plasma Glucose, and Lactate Changes following Aerobic Exhaustive Incremental Exercise in Trained 18-26 Years Old Men

In Vivo Antistress Effects of Synthetic Flavonoids in Mice: Behavioral and Biochemical Approach.

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones (F1–F6) and flavonols (OF1–OF6), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC50 of 31.46 ± 1.46 μg/mL and 25.54 ± 1.21 μg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC50 values of 174.24 ± 2.71 μg/mL and 122.33 ± 1.98 μg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion in mice

Objective: To explore the effect of metformin combined with intermittent fasting on endoplasmic reticulum stress after cerebral ischemia-reperfusion injury in mice. Methods: One hundred 10-Week-old healthy KM mice of SPF grade, weighing 25-28 g, were divided into 5 groups by the random number table method: sham group, focal cerebral ischemia group (I/R group), intermittent fasting group (IF group), metformin group (Met group), metformin+intermittent fasting group (Met+IF group). In IF group, food was provided ad libitum from 8∶00 to 16∶00 daily, but the mice were fasted for the rest of the time. In Met group, the mice underwent intraperitoneal injection of metformin (10 mg/kg). In Met+IF group, the mice received the same eating method as the IF group and the same method of metformin injection as Met Group. In Sham group, I/R group and IF group, the mice were intraperitoneally injected with equal volume of normal saline. Mice in all groups were not restricted to drinking water. Random plasma glucose and body weight changes in mice during preconditioning were monitored, and a focal cerebral ischemia-reperfusion model was established 14 days later. The cerebral infarction volume was measured after 1 hour of ischemia and 24 hours of reperfusion. The brain tissues of mice were subjected to Western blot to detect the contents of endoplasmic reticulum stress-related proteins, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and apoptosis proteins (Caspase-3 and Cleaved-caspase 3). Results: After different interventions, there was no significant difference in random plasma glucose changes among the four groups (all P<0.05). The blood glucose level of the mice in the Met+IF group was lower than the sham group, I/R group, IF group and Met group (all P<0.05). GRP78/β-actin in sham group, I/R group, IF group, Met group, IF+Met group were 0.48±0.05, 1.35±0.10, 0.94±0.05, 0.70±0.14, 0.41±0.37, respectively; CHOP/β-actin were 0.27±0.04, 1.03±0.03, 0.72±0.04, 0.63±0.04, 0.44±0.01, respectively; Caspase-3/β-actin were 0.51±0.04, 1.04±0.04, 0.83±0.03, 0.76±0.03, 0.63±0.05, respectively; Cleaved-Caspase-3/β-actin were 0.17±0.06, 1.01±0.20, 0.75±0.06, 0.51±0.12, 0.29±0.08, respectively, with statistically significant differences (all P<0.001). The counts of GRP78-positive cells in the hippocampus immunohistochemistry in the sham group, I/R group, IF group, Met group, and IF+Met group were 53±5, 192±11, 162±12, 140±10, 114±13, respectively, while the counts of CHOP-positive cells were 35±4, 177±12, 120±12, 100±7, 69±10, respectively, with statistically significant differences (all P<0.001). The relative volume of cerebral infarction in I/R group, IF group, Met group and IF+Met group were 0, 0.333±0.046, 0.258±0.023, 0.116±0.039, 0.111±0.039, respectively, and there were statistically significant differences (all P<0.001). Conclusion: Both Metformin and intermittent fasting can alleviate endoplasmic reticulum stress after cerebral ischemia and reperfusion in mice, and the combination of the two has a better effect.

Efficacy and immunogenicity of insulin biosimilar compared to their reference products: a systematic review and meta-analysis

BackgroundTo ascertain the efficacy, safety, and immunogenicity from existing evidence via conducting a meta-analysis of randomized controlled trials between biosimilar and originator insulins.MethodsThe PubMed, Cochrane Library, EMBASE, and ClinicalTrails.gov were searched to identify head-to-head randomized controlled trials (RCTs) that directly compare the efficacy and safety of biosimilar insulin and its originator. Efficacy was assessed by change of HbA1C, fasting plasma glucose (laboratory or self-monitoring of blood glucose (SMBG)), and change all mean of 7 points- or 8 points- SMBG. Safety was assessed by change in proportion hypoglycemia and serious hypoglycemia. The occurrence of anti-insulin antibodies (AIAs) was also evaluated.ResultsFourteen RCTs with 6188 patients from different countries were included. Data were pooled using a random-effects model and were expressed as the mean difference (MD), odds ratio (OR), and 95% confidence interval (CI). In efficacy, Insulin biosimilar products showed similar in change of HbA1C at weeks 26 and 52, the MD were 0.03 (95% CI − 0.02 to 0.07, p = 0.28), and 0.05 (95% CI − 0.05 to 0.15, p = 0.36), respectively. The proportion of HbA1C less than 7% at endpoint, the OR were 1.04 (95% CI 0.89 to 1.20, p = 0.64). The change of fasting plasma glucose (laboratory or SMBG) mmol/L in 24–52 weeks and change all mean of 7 points−/8 points- SMBG mmol/L in 24–52 weeks, the MD were 0.02 (95% CI − 0.20 to 0.24, p = 0.87) and − 0.34 (95% CI − 1.35 to 0.67, p = 0.51), respectively. In occurrence of hypoglycemia (≥ 1 events) and severe hypoglycemia, the OR were 0.96 (95% CI 0.85 to 1.09, p = 0.52) and 1.06 (95% CI 0.85 to 1.31, p = 0.62). The AIA was 1.02 (95% CI 0.90 to 1.16, p = 0.76). Analysis stratified by type of diabetes and duration of insulin. There was no significant difference between the biosimilar and their reference group in a different type of diabetes and different duration of insulin.ConclusionsInsulin biosimilar showed comparable characteristics with the reference drug in terms of efficacy, safety, immunogenicity, through comprehensive and specific conventional meta-analysis.

Adopting a High-Polyphenolic Diet Is Associated with an Improved Glucose Profile: Prospective Analysis within the PREDIMED-Plus Trial.

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 ± 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D.

Association between glucagon-like peptide-1 receptor gene polymorphism and treatment response to GLP1R agonists in Chinese patients with type 2 diabetes: a prospective cohort study.

Clinical response to glucagon-like peptide-1 receptor agonists (GLP1RAs) varies considerably among patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to examine the potential association between the genetic variants in GLP1R gene polymorphism with the therapeutic efficacy as well as gastrointestinal adverse drug reactions (ADRs) of GLP1RAs in Chinese T2DM patients. Adult T2DM patients were eligible to participate in this prospective cohort study. Subjects received 12-week treatment with either exenatide (20μg/day) or liraglutide (1.2mg/day). GLP1R rs10305420 and rs3765467 genotyping was performed using the Sanger sequencing method. Clinical response to GLP1RAs was assessed in the patients who completed the 12-week treatment and defined by the change of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and body mass index (BMI) from the baseline. A total of 176 subjects (mean age 50.9 ± 12.7years, 111 men) were enrolled. The planned 12-week treatment was completed by 156 patients. HbA1c reduction was significantly larger in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (1.7% ± 2.4% vs. 0.8% ± 1.8%; P = 0.002). Similarly, the 7.0% target HbA1c attainment rate was significantly higher in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (50.9% vs. 23.8%; P = 0.002). Gastrointestinal ADRs did not differ significantly among different genotypes. GLP1R rs3765467 polymorphism is associated with therapeutic response to GLP1RAs in Chinese T2DM patients. HbA1c reduction is more pronounced in subjects with the GG genotype.

Circulating Levels of microRNA-122 and Hepatic Fat Change in Response to Weight-Loss Interventions: CENTRAL Trial.

Little is known about the relations between changes in circulating microRNA-122 (miR-122) and liver fat in response to weight-loss interventions. We aimed to investigate the association between miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. The CENTRAL trial is an 18-month randomized, controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat diet or a Mediterranean/low-carbohydrate diet. After 6 months of dietary intervention, each diet group was further randomized into added physical activity groups or no added physical activity groups for the following 12 months of intervention. The current study included 220 participants at baseline and 134 participants with repeated measurements on serum miR-122 and hepatic fat content over 18 months. Serum miR-122 significantly increased from baseline to 18 months, while no difference was observed across the 4 intervention groups. We found a significant association between miR-122 and hepatic fat content at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content (P < 0.001). Furthermore, we found that higher elevations in miR-122 were associated with less reductions in hepatic fat percentage during 18-month interventions (β = 1.56, P = 0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months (P interaction = 0.02). Our data indicate that participants with higher elevation in serum miR-122 may benefit less in reduction of hepatic fat content in response to diet and physical activity interventions.

Intermittent administration of peracetic acid is a mild environmental stressor that elicits mucosal and systemic adaptive responses from Atlantic salmon post-smolts

BackgroundFish encounter oxidative stress several times during their lifetime, and it has a pervasive influence on their health and welfare. One of the triggers of oxidative stress in fish farming is the use of oxidative disinfectants to improve rearing conditions, especially in production systems employing recirculation technology. Here we report the physiological and morphological adaptive responses of Atlantic salmon (Salmo salar L.) post-smolts to intermittent exposure to a potent oxidative agent peracetic acid (PAA). Fish reared in semi-commercial scale brackish water recirculating aquaculture system (RAS) were exposed to 1 ppm PAA every 3 days over 6 weeks. Mucosal and systemic responses were profiled before exposure, 22 and 45 days during the intermittent PAA administration.ResultsOxidative stress was likely triggered as plasma antioxidant capacity increased significantly during the exposure period. Adaptive stress response to the periodic oxidant challenge was likewise demonstrated in the changes in plasma glucose and lactate levels. PAA-induced alterations in the transcription of antioxidants, cytokines, heat shock proteins and mucin genes showed a tissue-specific pattern: downregulation was observed in the gills and olfactory rosette, upregulation occurred in the skin, and no substantial changes in the liver. Further, PAA exposure resulted in histological changes in key mucosal organs (i.e. olfactory rosette, skin and gills); pathological alterations were predominant in the gills where cases of epithelial lifting, hypertrophy and clubbing were prevalent. In addition, intermittent PAA administration resulted in an apparent overproduction of mucus in the nasal mucosa. Lastly, PAA did not dramatically alter the ability of salmon to mount a physiological stress response in the presence of a secondary stressor, though some subtle interference was documented in the kinetics and magnitude of plasma cortisol and glucose response post-stress.ConclusionsThe present study collectively demonstrated that intermittent oxidant exposure was a mild environmental stressor that salmon could mount strong adaptive responses at systemic and mucosal levels. The results will be valuable in optimising the rearing conditions of post-smolts in RAS, especially in adopting water treatment strategies that do not considerably interfere with fish health and welfare.

Real-world Retrospective Assessment of Initiation and Effectiveness of Dual Combination Therapy with Metformin and Teneligliptin in Drug Naïve Indian Type 2 Diabetes Mellitus Patients (INITIATE)

Introduction: Diabetes Mellitus (DM) has become the leading health concern worldwide over the last few decades. But despite advances in both understanding of the pathophysiology of Type 2 Diabetes Mellitus (T2DM), and the development of new treatment strategies, current management of patients with T2DM remains suboptimal. Initial monotherapy is frequently inadequate in patients with high baseline Glycated Haemoglobin (HbA1c). Thus, initial combination therapy has emerged as an alternative approach. Aim: To assess INItiation and effecTiveness of dual combInation therapy with metformin And Teneligliptin in drug naïvE T2DM patients (INITIATE). Materials and Methods: In this retrospective, multicentre study, newly diagnosed drug naïve T2DM patients failed with diet and exercise prior to screening and initiated with dual therapy of metformin and teneligliptin were enrolled. Data of all the patients prescribed with any therapeutic dose of metformin (250 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg) and teneligliptin (20 mg, 40 mg) was considered. The data was analysed to assess change in glycaemic parameters from baseline to 12 weeks. Paired t-test was applied for statistical results. Results: Data of 7857 patients were analysed. The mean change of Fasting Plasma Glucose (FPG) from baseline {202.29±52.2 mg/dL (11.23±2.89 mmol/L)} to 12 weeks {142.57±34.5 mg/dL (7.91±1.91 mmol/L)} was -59.72±17.7 mg/dL (-3.31±0.98 mmol/L) (p-value &lt;0.0001). The absolute change in mean Postprandial Plasma Glucose (PPG) from baseline {(286.26±80.43 mg/dL (15.89±4.46 mmol/L)} to 12 weeks {(198.30±42.24 mg/dL (11±2.34 mmol/L)} was -87.96±38.19 mg/dL (-4.88±2.12 mmol/L) (p-value &lt;0.0001). Mean HbA1c level was 8.11%±1% (65±10.9 mmol/mol) at baseline and decreased significantly to 7.15%±0.94% (55±10.3 mmol/mol) (p-value &lt;0.0001) with a mean change of -0.96±0.06 (-10.5±0.7 mmol/mol) at 12 weeks. Total 42.83% (n=3365) patients achieved target HbA1c (&lt;7%) at 12 weeks. Conclusion: Initiation of dual therapy with metformin and teneligliptin in drug naïve Indian T2DM patients significantly improved glycaemic control.

Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice.

PurposeThis study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.Materials and MethodsThe study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment.ResultsThe baseline HbA1c was 8.3±1.3% (8.7±1.5% in the add-on group and 8.1±1.0% in the switch group). After 12 months, mean HbA1c decreased (-0.91%) in all patients (p<0.05) (-1.39% in the add-on group and -0.63% in the switch group). Significant reductions in FPG were also observed in both the add-on and switch groups (-54.37 mg/dL and -24.68 mg/dL, respectively). Overall, there was a significant improvement in serum triglyceride (-24.74 mg/dL), low density lipoprotein cholesterol (-7.92 mg/dL), body weight (-2.98 kg), VFA (-9.00 cm2), and systolic blood pressure (-8.67 mm Hg). Approximately 35.8% of patients achieved HbA1c <7.0% after 12 months.ConclusionDapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Effect of nanocurcumin on serum levels of betatrophin and irisin in patients with metabolic syndrome; a clinical trial

Introduction: Metabolic syndrome is a highly prevalent disease with combination of cardio metabolic risk factors. Insulin resistance is the most important reason of metabolic syndrome. Objectives: The study aimed to evaluate the effects of nanocurcumin on insulin resistance and serum level irisin and betatrophin in patients with metabolic syndrome. Patients and Methods: Sixty metabolic syndrome patients (30 males and 30 females) received 80 mg/daily nanocurcumin for three months. The samples of fasting blood were collected at the beginning of the study and after 90-days intervention to measure the biomarkers. Results: comparing pre and post treatment with nanocurcumin values revealed a significant change in fasting plasma glucose (FPG), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and irisin (P&gt;0.05), but there was no change in the amount of betatrophin (P&gt;0.05). Conclusion: According to the results, it seems that the use of nanocurcumin for 90 days may have positive effects on some metabolic components. However, more studies with larger sample sizes are needed to confirm the findings. Trial registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20120215009014N214; https:// www.irct.ir/trial/30187, ethical code; IR.UMSHA.REC.1396.859).

Changes in serum copeptin in the early onset of type 2 diabetes

Copeptin (C-terminal fragment of pro-arginine vasopressin) levels change as fasting plasma glucose (FPG) and blood pressure change. To explore the clinical significance of changes in copeptin levels in development of type 2 diabetes mellitus (T2DM), we enrolled patients undergoing physical health examinations who met diagnostic criteria for prediabetes and T2DM. Subjects were divided into eight subgroups based on FPG levels and presence or absence of hypertension, including: a normal group (NGT), FPG &lt; 5.6 mmol/L; prediabetes A, 5.6 mmol/L ≤ FPG &lt; 6.1 mmol/L; prediabetes B, 6.1 mmol/L ≤ FPG &lt; 7.0 mmol/L; and T2DM, FPG ≥ 7.0 mmol/L; participants were further into two subgroups by whether they had hypertension or not. Measures included biochemical indicators, fasting insulin (FINS), and copeptin. Copeptin levels in prediabetes A, prediabetes B, and T2DM groups increased significantly compared to NGT group ( P &lt; 0.01). No significant differences were found in copeptin levels between normal blood pressure and hypertension subgroups in all four groups. Copeptin levels correlated positively with systolic blood pressure, glycosylated hemoglobin (HbA1c), FPG, FINS, and insulin resistance index (HOMA-IR; P &lt; 0.05–0.001), and negatively with insulin secretion index ( P &lt; 0.05–0.001). Stepwise regression analysis revealed that copeptin levels correlated independently with elevated HbA1c and aggravated HOMA-IR ( P &lt; 0.001). Increase in copeptin levels may aggravate insulin resistance, finally leading to T2DM.

Changes in objectively-measured physical capability over 4-year, risk of diabetes, and glycemic control in older adults: The China Health and Retirement Longitudinal study

AimsHigh physical capability reduces risk of diabetes, but the association of its changes with risk of diabetes and glycemic control is unclear in older adults. This study aimed to quantify their association. MethodsA total of 1,667 participants without diabetes and aged ≥ 60 years from the China Health and Retirement Longitudinal Study were included and followed over 4 years. Physical capability was objectively measured at baseline and 4-year later. Logistic regression models were used to assess the association of changes in physical capability with risk of diabetes. ResultsDuring follow-up, 160 participants developed diabetes. None of the changes in physical capability expressed in continuous scales or in tertiles was associated with risk of diabetes in unadjusted or adjusted models (all P > 0.05), and no favorable joint effects were observed. Changes in physical capability were not associated with changes in fasting plasma glucose or hemoglobin A1c. Yet increases in walking speed or grip strength were related to reduced metabolic score for insulin resistance (both P ≤ 0.03). ConclusionsIncreases in objectively-measured physical capability were not associated with reduced risk of diabetes but may ameliorate insulin resistance in older adults. Studies with longer follow-up periods are required to confirm these findings.

Association of fasting plasma glucose change trajectory and risk of hypertension: a cohort study in China.

We aimed to assess the association between fasting plasma glucose (FPG) change trajectory and incident hypertension among Chinese population. This cohort study included 11,791 adults aged 18–80 years without hypertension at first entry and who completed at least four follow-ups between 2009 and 2016. Logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the association between FPG change trajectory and probability of hypertension. During a median follow-up of 5.10 years (total person–years 61,887.76), hypertension developed in 2177 participants. After adjusting for baseline potential confounders, the probability of hypertension increased with the increasing FPG change trajectory (adjusted OR (aOR) 1.22, 95% CI 1.07–1.40), bell-shape trajectory (aOR 1.15, 95% CI 1.02–1.30) and other-shape trajectory (aOR 1.13, 95% CI 1.02–1.25) which showed a higher variability of FPG compared to the decreasing group. In addition, the increasing FPG change trajectory was associated with a higher probability of hypertension compared with the decreasing group regardless of age and BMI but was only significant in males and in those with normal FPG at baseline. Our study indicates that the increasing FPG change trajectory determines the highest risk of hypertension, demonstrating the importance of maintaining low and stable levels of FPG, especially in males and in those with normal FPG.

Timing of Meals and Exercise Affects Hormonal Control of Glucoregulation, Insulin Resistance, Substrate Metabolism, and Gastrointestinal Hormones, but Has Little Effect on Appetite in Postmenopausal Women.

The current prevalence of obesity in the US is strongly associated with excessive food intake and insufficient physical activity. This study examined whether changing the timing of exercise before or after two daily meals could alter human appetite for food. Fifty-four healthy postmenopausal women were matched by body weight and assigned to two groups: (1) two bouts of 2-h moderate-intensity exercise ending one hour before each weight-maintenance meal (XM, n = 23), (2) two-hour moderate-intensity exercise starting 1 h after each weight-maintenance meal (MX, n = 23), and one sedentary control (SED) arm (n = 8). Measurements included appetite ratings, circulating glucose, free fatty acids (FFAs), a ketone body D-ß-hydroxybutyrate (BHB), glucoregulatory hormones insulin and glucagon, and gastrointestinal hormones associated with food digestion and absorption and implicated in appetite sensations. XM group increased concentrations of FFAs and BHB during exercise and increased insulin and homeostatic assessment of insulin resistance (HOMA-IR) during postprandial periods. MX group reduced postprandial insulin and HOMA-IR by about 50% without a major change in plasma glucose. There was brief suppression of hunger and an increase in satiation in both exercise groups near the end of the first postprandial period. The time course of hunger was unrelated to the perturbations in fuel metabolism, depletion of liver glycogen, and not correlated with concentration changes in hunger-stimulating hormone ghrelin during XM exercise before meals. Similarly, there was no correlation between the time course of fullness during exercise after meals with the postprandial secretion of gastrointestinal hormones including cholecystokinin (CCK) that has been linked to satiation. Hunger and satiation appear to depend on oral intake and gastrointestinal processing of nutrients and are not affected by metabolic and hormonal consequences of the timing of exercise with respect to meals. Moderate-intensity exercise performed shortly after meals induces a rapid and highly effective lowering of insulin resistance.