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The effect of frequency of activity interruptions in prolonged sitting on postprandial glucose metabolism: A randomized crossover trial.
Thorsen, IK, Johansen, MY, Pilmark, NS, Jespersen, NZ, Brinkløv, CF, Benatti, FB, Dunstan, DW, Karstoft, K, Pedersen, BK, Ried-Larsen, M
Metabolism: clinical and experimental. 2019;:1-7
Abstract
OBJECTIVE The primary objective was to test the hypothesis that increased frequency of interruptions in prolonged sitting reduces postprandial glycemia independent of energy intake and expenditure. MATERIALS/METHODS Healthy, sedentary, centrally obese men (n = 14; age*, 28.2 (23.4; 38.3) years; BMI, 31.9 ± 6.7 kg/m2; VO2max*, 39.5 (38.8; 40.9) ml/min/kg; HbA1c, 5.3 ± 0.4% (34.1 ± 4.2 mmol/mol); mean ± SD (*median (25th; 75th percentile)) completed four 8-h interventions in randomized order: 1) uninterrupted sitting (SIT), 2) sitting interrupted by 2 min of walking (~30% of VO2max) every 20th minute (INT20), 3) sitting interrupted by 6 min of walking every hour (INT60), and 4) sitting interrupted by 12 min of walking every second hour (INT120). A standardized test drink was served at the beginning of and 4 h into the intervention (total of 2310 ± 247 kcal; 50% energy from carbohydrate, 50% energy from fat). Outcomes included the difference in the 8-h total area under the curve (tAUC) for primarily plasma glucose, and secondarily plasma insulin and C-peptide during INT20, INT60, and INT120 compared to SIT. RESULTS No difference [95% CI] was observed in the primary outcome, the 8-h tAUC for the plasma glucose, during INT20, INT60, and INT120 compared to SIT (-65.3 mmol/l∗min [-256.3; 125.7], +53.8 mmol/l∗min [-143.1; 250.8], and +18.6 mmol/l∗min [-172.4; 209.6], respectively). CONCLUSIONS Interrupting sitting with increasing frequency did not reduce the postprandial plasma glucose response to prolonged sitting in healthy, sedentary, centrally obese men.
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Clinical pharmacology study of ipragliflozin in Japanese patients with type 1 diabetes mellitus: A phase 2, randomized, placebo-controlled trial.
Kaku, K, Isaka, H, Toyoshima, J, Sakatani, T
Diabetes, obesity & metabolism. 2019;(6):1445-1454
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Abstract
AIM: To evaluate the pharmacodynamics, pharmacokinetics, and safety of the novel oral sodium-glucose co-transporter-2 inhibitor, ipragliflozin, in Japanese patients with type 1 diabetes mellitus. MATERIALS AND METHODS We conducted a multicentre, double-blind, placebo-controlled, parallel-group study. Patients were randomized to receive 25, 50, or 100 mg/day ipragliflozin or placebo for 2 weeks. Key pharmacokinetic endpoints included area under the concentration-time curve 24 hours postdose (AUC24h ), maximum plasma concentration (Cmax ), and renal clearance. Key pharmacodynamic endpoints included 24-hour urinary glucose excretion, mean plasma glucose AUC0-24h , and mean renal glucose clearance. Changes in total, basal, and bolus insulin dosages were recorded. Adverse events (AEs) were monitored for safety. RESULTS Dose-dependent increases were observed in AUC24h and Cmax on days 1 and 14 for 25-, 50-, and 100-mg ipragliflozin. The mean plasma glucose AUC0-24h was lower than that of placebo and the mean renal glucose clearance increased in a dose-dependent manner from baseline, but remained unchanged in the placebo group. The mean (standard deviation) change from baseline in total daily insulin dose was greater in the ipragliflozin 25-, 50-, and 100-mg groups (-14.77 ± 14.04%, -18.40 ± 12.49% and -19.25 ± 16.77%, respectively), than placebo (-4.51 ± 16.28%). Most AEs were mild in severity; no patients discontinued the study because of treatment-emergent AEs. CONCLUSIONS The pharmacokinetic and pharmacodynamic properties of ipragliflozin in Japanese patients with type 1 diabetes mellitus were confirmed. Increases in urinary glucose excretion lead to dose-dependent decreases in plasma glucose. Concomitant insulin dose decreased with ipragliflozin treatment. No clinically relevant safety concerns were identified.
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The effect of saffron supplementation on blood glucose and lipid profile: A systematic review and meta-analysis of randomized controlled trials.
Asbaghi, O, Soltani, S, Norouzi, N, Milajerdi, A, Choobkar, S, Asemi, Z
Complementary therapies in medicine. 2019;:102158
Abstract
BACKGROUND Despite several studies about the effects of saffron supplementation on serum concentrations of lipid and glucose profiles, no systematic study had summarized the findings. Therefore, we conduct current study to systematically summarize findings from studies about the effect of saffron supplementation on serum levels of glucose and lipid profiles and to do a meta-analysis, if possible. METHODS A systematic literature search was conducted for clinical trials published in PubMed, SCOPUS, EMBASE, Cochrane's Library and ISI Web of Science from the beginning to 22 February 2019. All randomized clinical trials on the effect of saffron supplementation on serum concentrations of lipid and glucose profiles were included. RESULTS In overall, six studies were included in the current study. Pooled analysis of six studies for the effect of saffron on serum TG, TC and FBG concentrations and of five studies for LDL and HDL, showed a significant reduction in TG (WMD: -8.93 mg/dl; 95% CI: -16.49 to -1.37, P = 0.02) and TC levels (WMD: -5.72 mg/dl; 95% CI: -11.10 to -0.34, P = 0.03), a significant increase in HDL levels (WMD: 2.7 mg/dl; 95% CI: 0.22 to 5.18, P = 0.03), and no significant effect on LDL (WMD: -2.30 mg/dl; 95% CI: -11.73 to 7.13, P = 0.63) and FBG levels (WMD: -5.30 mg/dl; 95% CI: -14.20 to 3.60, P = 0.51). CONCLUSION We found a significant reduction in serum concentrations of TC and TG and a significant increase in serum levels of HDL following supplementation with saffron. Saffron supplementation had no significant influence on serum FPG and LDL concentrations.
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Regulation of glucose metabolism by bioactive phytochemicals for the management of type 2 diabetes mellitus.
Zhao, C, Yang, C, Wai, STC, Zhang, Y, P Portillo, M, Paoli, P, Wu, Y, San Cheang, W, Liu, B, Carpéné, C, et al
Critical reviews in food science and nutrition. 2019;(6):830-847
Abstract
Type 2 diabetes mellitus (T2DM) is the most prevalent disease and becoming a serious public health threat worldwide. It is a severe endocrine metabolic disorder that has the ability to induce serious complications in all kinds of organs. Although mechanisms of anti-diabetics have been described before, we focus here on the cellular and physiological mechanisms involved in the modulation of insulin and glucose blood levels. As obesity and inflammation are intimately associated with the development of T2DM, their possible relationships are also described. The effects of gut microbiota on insulin resistance have been recently investigated in clinical trials, and we discuss the potential mechanisms by which gut microbiota may improve glucose handling, especially via the metabolism of ingested phytochemicals. Among the historically supported effects of phytochemicals, their therapeutic potential for T2DM leads to consider these natural products as an important pool for the identification of novel anti-diabetic drug leads. This current research extends the descriptions of anti-diabetic effects of plants that are used in traditional medicines or as nutraceuticals. The objective of the present review is to make a systematic report on glucose metabolism in T2DM as well as to explore the relationships between natural phytochemicals and glucose handling.
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Modest changes to glycemic regulation are sufficient to maintain glucose fluxes in healthy young men following overfeeding with a habitual macronutrient composition.
Morrison, DJ, Kowalski, GM, Bruce, CR, Wadley, GD
American journal of physiology. Endocrinology and metabolism. 2019;(6):E1061-E1070
Abstract
Currently, it is unclear whether short-term overfeeding in healthy people significantly affects postprandial glucose regulation, as most human overfeeding studies have utilized induced experimental conditions such as the euglycemic-hyperinsulinemic clamp technique to assess glucoregulation. The aim of this study was to quantify glucose fluxes [rates of meal glucose appearance (Ra), disposal (Rd), and endogenous glucose production (EGP)] in response to 5 and 28 days of overfeeding (+45% energy) while maintaining habitual macronutrient composition (31.0 ± 1.9% fat, 48.6 ± 2.2% carbohydrate, 16.7 ± 1.4% protein) in healthy, lean young men. Meal tolerance testing was combined with the triple-stable isotope glucose tracer approach. Visceral adipose volume increased by ~15% with 5 days of overfeeding, while there was no further change at 28 days. In contrast, body mass (+1.6 kg) and fat mass (+1.3 kg) were significantly increased only after 28 days of overfeeding. Fasting EGP, Rd, and insulin were increased at 5 but unchanged after 28 days. Postprandial glucose and insulin responses were unaltered by 5 days of overfeeding but were modestly increased after 28 days (P < 0.05). However, meal Ra and glucose Rd were significantly increased after both 5 and 28 days of overfeeding (P < 0.05). Despite this, overfeeding did not lead to alterations to postprandial EGP suppression. Thus, in contrast to findings from euglycemic-hyperinsulinemic clamp studies, chronic overfeeding did not affect the ability to suppress EGP or stimulate Rd under postprandial conditions. Rather, glucose flux was appropriately maintained following 28 days of overfeeding through modest increases in postprandial glycemia and insulinemia.
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Serum Glucose and Potassium Ratio as Risk Factors for Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage.
Matano, F, Fujiki, Y, Mizunari, T, Koketsu, K, Tamaki, T, Murai, Y, Yokota, H, Morita, A
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2019;(7):1951-1957
Abstract
OBJECTIVE Cerebral vasospasm is associated with poor prognosis in patients with aneurysmal subarachnoid hemorrhage (SAH), and biomarkers for predicting poor prognosis have not yet been established. We attempted to clarify the relationship between serum glucose/potassium ratio and cerebral vasospasm in patients with aneurysmal SAH. METHODS We studied 333 of 535 aneurysmal SAH patients treated between 2006 and 2016 (123 males, 210 females; mean age 59.7 years; range 24-93). We retrospectively analyzed the relationship between cerebral vasospasm grade and clinical risk factors, including serum glucose/potassium ratio. RESULTS Postoperative angiography revealed cerebral vasospasm in 112 patients (33.6%). Significant correlations existed between the ischemic complication due to cerebral vasospasm and glucose/potassium ratio (P < .0001), glucose (P = .016), and potassium (P = .0017). Serum glucose/potassium ratio was elevated in the cerebral vasospasm grade dependent manner (Spearman's r = 0.1207, P = .0279). According to the Glasgow Outcome Scale (GOS) score at discharge, 185 patients (55.5%) had a poor outcome (GOS scores 1-3). Serum glucose/potassium ratio was significantly correlated between poor outcome (GOS scores 1-3) and age (P < .0001), serum glucose/potassium ratio (P < .0001), glucose (P < .0001), potassium (P = .0004), white blood cell count (P = .0012), and cerebral infarction due to cerebral vasospasm (P < .0001). Multivariate logistic regression analyzes showed significant correlations between cerebral infarction due to cerebral vasospasm and serum glucose/potassium ratio (P = .018), glucose (P = .027), and potassium (P = .052). CONCLUSIONS Serum glucose/potassium ratio in cases of aneurysmal SAH was significantly associated with cerebral infarction due to cerebral vasospasm and GOS at discharge. Therefore, this factor was useful to predict prognosis in patients with cerebral vasospasm and aneurysmal SAH.
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Urinary glucose excretion after dapagliflozin treatment: An exposure-response modelling comparison between Japanese and non-Japanese patients diagnosed with type 1 diabetes mellitus.
Sokolov, V, Yakovleva, T, Ueda, S, Parkinson, J, Boulton, DW, Penland, RC, Tang, W
Diabetes, obesity & metabolism. 2019;(4):829-836
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Abstract
AIMS: To assess the dapagliflozin exposure-response relationship in Japanese and non-Japanese patients with type 1 diabetes mellitus (T1DM) and investigate if a dose adjustment is required in Japanese patients. MATERIALS AND METHODS Data from two clinical studies were used to develop a non-linear mixed effects model describing the relationship between dapagliflozin exposure (area under the concentration curve) and response (24-hour urinary glucose excretion [UGE]) in Japanese and non-Japanese patients with T1DM. The effects of patient-level characteristics (covariates; identified using a stepwise procedure) on response was also assessed. Simulations were performed using median-normalized covariate values. RESULTS Data from 84 patients were included. Average self-monitored blood glucose (SMBG) at day 7, change from baseline in total insulin dose at day 7, and baseline estimated glomerular filtration rate (eGFR) all had a significant effect on 24-hours UGE, with SMBG being the most influential. Dapagliflozin systemic exposure for matching doses and baseline eGFR was similar between Japanese and non-Japanese patients; however, higher SMBG and a greater reduction in total insulin dose was observed in the Japanese population. When the significant covariates were included, the model fit the data well for both populations, and accurately predicted exposure-response in the Japanese and non-Japanese populations, in agreement with the observed data. CONCLUSIONS There was no difference in dapagliflozin exposure-response in Japanese and non-Japanese patients with T1DM once differences in renal function, glycaemic control and insulin dose reductions between studies were considered. Therefore, no dose adjustment is recommended in Japanese patients with T1DM.
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Is fasting plasma glucose in early pregnancy a better predictor of adverse obstetric outcomes than glycated haemoglobin?
Mañé, L, Flores-Le Roux, JA, Pedro-Botet, J, Gortazar, L, Chillarón, JJ, Llauradó, G, Payà, A, Benaiges, D
European journal of obstetrics, gynecology, and reproductive biology. 2019;:79-84
Abstract
OBJECTIVES To determine, in a multi-ethnic cohort, the suitability of first-trimester fasting plasma glucose and HbA1c levels in non-diabetic range to identify women without diabetes at increased pregnancy risk. STUDY DESIGN A retrospective analysis of a prospective cohort between April 2013 and September 2015. Universal testing for fasting plasma glucose and HbA1c levels at the first antenatal blood sampling was performed and women were screened for gestational diabetes mellitus at 24-28 weeks' gestation. Primary outcomes were macrosomia and pre-eclampsia, and secondary outcomes preterm delivery, Caesarean section and large-for-gestational age. Different fasting plasma glucose and HbA1c cut-off levels were assessed for associations with outcomes. RESULTS 1,228 pregnancies were included for outcome analysis. After adjustment for potential confounders, no association was found between fasting plasma glucose levels and pregnancy outcomes. Women with an HbA1c ≥5.8% (39.9 mmol/mol) showed an increased risk of macrosomia (OR 2.69, 95% CI 1.16-6.24); an HbA1c ≥5.9% (41 mmol/mol) threshold was independently associated with a three-fold risk of pre-eclampsia (95% CI 1.03-9.9) and an HbA1c ≥6.0% (42.1 mmol/mol) with a four-fold risk of large-for-gestational age (95% CI 1.49-11.07). CONCLUSIONS In a multi-ethnic population, first-trimester fasting plasma glucose levels were not a better predictor of pregnancy complications than HbA1c. Further, an early HbA1c ≥5.8% (39.9 mmol/mol) threshold is already associated with an increased risk of macrosomia.
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Pharmacokinetics, Pharmacodynamics, and Modulation of Hepatic Glucose Production With Insulin Glargine U300 and Glargine U100 at Steady State With Individualized Clinical Doses in Type 1 Diabetes.
Porcellati, F, Lucidi, P, Candeloro, P, Cioli, P, Marinelli Andreoli, A, Curti, G, Bolli, GB, Fanelli, CG
Diabetes care. 2019;(1):85-92
Abstract
OBJECTIVE This study characterized the pharmacokinetics (PK), pharmacodynamics (PD), and endogenous (hepatic) glucose production (EGP) of clinical doses of glargine U300 (Gla-300) and glargine U100 (Gla-100) under steady-state (SS) conditions in type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS T1DM subjects (N = 18, age 40 ± 12 years, T1DM duration 26 ± 12 years, BMI 23.4 ± 2 kg/m2, A1C 7.19 ± 0.52% [55 ± 5.7 mmol · mol-1-1]) were studied after 3 months of Gla-300 or Gla-100 (evening dosing) titrated to fasting euglycemia (random, crossover) with the euglycemic clamp using individualized doses (Gla-300 0.35 ± 0.08, Gla-100 0.28 ± 0.07 units · kg-1). RESULTS Plasma free insulin concentrations (free immunoreactive insulin area under the curve) were equivalent over 24 h with Gla-300 versus Gla-100 (point estimate 1.11 [90% CI 1.03; 1.20]) but were reduced in the first 6 h (0.91 [90% CI 0.86; 0.97]) and higher in the last 12 h postdosing (1.38 [90% CI 1.21; 1.56]). Gla-300 and Gla-100 both maintained 24 h euglycemia (0.99 [90% CI 0.98; 1.0]). The glucose infusion rate was equivalent over 24 h (1.03 [90% CI 0.88; 1.21]) but was lower in first (0.77 [90% CI 0.62; 0.95]) and higher (1.53 [90% CI 1.23; 1.92]) in the second 12 h with Gla-300 versus Gla-100. EGP was less suppressed during 0-6 h but more during 18-24 h with Gla-300. PK and PD within-day variability (fluctuation) was 50% and 17% lower with Gla-300. CONCLUSIONS Individualized, clinical doses of Gla-300 and Gla-100 resulted in a similar euglycemic potential under SS conditions. However, Gla-300 exhibited a more stable profile, with lower variability and more physiological modulation of EGP compared with Gla-100.
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Body Weight Reduction of 5% Improved Blood Pressure and Lipid Profiles in Obese Men and Blood Glucose in Obese Women: A Four-Year Follow-up Observational Study.
Hasegawa, Y, Nakagami, T, Oya, J, Takahashi, K, Isago, C, Kurita, M, Tanaka, Y, Ito, A, Kasahara, T, Uchigata, Y
Metabolic syndrome and related disorders. 2019;(5):250-258
Abstract
Background: Body weight reduction (BWR) of at least 3% in obese Japanese individuals through lifestyle interventions has improved the risk factors for cardiovascular disease (CVD). We aimed to assess the relation between body weight change (BWC) and CVD risk change and to identify lifestyle improvement related to BWR in obese Japanese individuals. Methods: Subjects were 2579 health checkup examinees without medicated diabetes, hypertension or dyslipidemia, and a body mass index ≥25 kg/m2 who completed lifestyle questionnaires in 2008 and 2012. The 4-year changes in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, and blood pressure (BP) levels were compared across the five groups based on the 4-year BWC, and presented as <-5%, -5% to -3%, -3% to -1%, -1% to 1%, and ≥1%. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for lifestyle improvement related to BWR. Results: Comparing the groups to the reference group (BWC ranging from -1% to +1%), we observed that FPG and HbA1c levels were lower in women in the <-5% group; BP levels were also lower in the <-5% group; triglyceride levels had improved in the <-3% group, and low-density lipoprotein cholesterol levels in the <-5% group; high-density lipoprotein cholesterol levels had improved in men in the <-5% group. In men, the adjusted OR (95% CI) for BWR related to lifestyle improvement pertaining to "over 30 min exercise" was 2.6 (2.0-3.6). In women, the adjusted ORs for BWR related to "walking or physical activity," "drinking alcohol," and "drinking more than a glass of sake" were 1.7 (1.1-2.7), 1.9 (1.1-3.5), and 1.8 (1.1-3.0), respectively. Conclusions: A 5% BWR improved FPG and HbA1c levels in obese women, and BP and lipid levels in obese men. Improvements in exercise and alcohol consumption habits were associated with BWR in this population.