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1.
Effect of Dapagliflozin in DAPA-HF According to Background Glucose-Lowering Therapy.
Docherty, KF, Jhund, PS, Bengtsson, O, DeMets, DL, Inzucchi, SE, Køber, L, Kosiborod, MN, Langkilde, AM, Martinez, FA, Sabatine, MS, et al
Diabetes care. 2020;(11):2878-2881
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Abstract
OBJECTIVE To determine whether the benefits of dapagliflozin in patients with heart failure and reduced ejection fraction (HFrEF) and type 2 diabetes in the Dapagliflozin And Prevention of Adverse-Outcomes in Heart Failure trial (DAPA-HF) varied by background glucose-lowering therapy (GLT). RESEARCH DESIGN AND METHODS We examined the effect of study treatment by the use or not of GLT and by GLT classes and combinations. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. RESULTS In the 2,139 type 2 diabetes patients, the effect of dapagliflozin on the primary outcome was consistent by GLT use or no use (hazard ratio 0.72 [95% CI 0.58-0.88] vs. 0.86 [0.60-1.23]; interaction P = 0.39) and across GLT classes. CONCLUSIONS In DAPA-HF, dapagliflozin improved outcomes irrespective of use or no use of GLT or by GLT type used in patients with type 2 diabetes and HFrEF.
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Predictors of the Acute Postprandial Response to Breaking Up Prolonged Sitting.
Henson, J, Edwardson, CL, Celis-Morales, CA, Davies, MJ, Dunstan, DW, Esliger, DW, Gill, JMR, Kazi, A, Khunti, K, King, J, et al
Medicine and science in sports and exercise. 2020;(6):1385-1393
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Abstract
PURPOSE To identify predictors of favorable changes to postprandial insulin and glucose levels in response to interrupting prolonged sitting time with standing or light-intensity physical activity. METHODS Data were combined from four similarly designed randomized acute cross-over trials (n = 129; body mass index [BMI] range, 19.6-44.6 kg·m; South Asian = 31.0%; dysglycemia = 27.1%). Treatments included: prolonged sitting (6.5 h) or prolonged sitting broken-up with either standing or light-intensity physical activity (5 min every 30 min). Time-averaged postprandial responses for insulin and glucose were calculated for each treatment (mean ± 95% confidence interval). Mutually adjusted interaction terms were used to examine whether anthropometric (BMI), demographic (age, sex, ethnicity [white European vs South Asian]) and a cardiometabolic variable (Homeostatic Model Assessment of Insulin Resistance)-modified responses. RESULTS Postprandial insulin and glucose were reduced when individuals interrupted prolonged sitting with bouts of light physical activity, but not with standing. Reductions in time-averaged postprandial insulin were more pronounced if individuals were South Asian compared with white European (-18.9 mU·L [-23.5%] vs -8.2 mU·L [-9.3%]), female compared with male (-15.0 mU·L [-21.2%] vs -12.1 mU·L [-17.6%]) or had a BMI ≥27.2 kg·m (-20.9 mU·L [-22.9%] vs -8.7 mU·L [-18.2%]). Similarly, being female (-0.4 mmol·L [-0.6 mmol·L, -0.2 mmol·L], -6.8% vs -0.1 mmol·L [-0.3 mmol·L, 1 mmol·L], -1.7%) or having a BMI ≥27.2 kg·m (-0.4 mmol·L [-0.6 mmol·L, -0.2 mmol·L], -6.7% vs -0.2 mmol·L [-0.4 mmol·L, 0.0 mmol·L], -3.4%) modified the postprandial glucose response. No significant interactions were found for Homeostatic Model Assessment of Insulin Resistance or age. CONCLUSIONS Being female, South Asian, or having a higher BMI, all predicted greater reductions in postprandial insulin, whereas being female and having a higher BMI predicted greater reductions in postprandial glucose when sitting was interrupted with light physical activity. These results could help to guide personalized interventions in high-risk participants for whom breaking prolonged sitting time with light activity may yield the greatest therapeutic potential.
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Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis.
Braunstein, CR, Noronha, JC, Khan, TA, Mejia, SB, Wolever, TM, Josse, RG, Kendall, CW, Sievenpiper, JL
Clinical nutrition (Edinburgh, Scotland). 2020;(11):3308-3318
Abstract
AIMS: To synthesize the evidence of the effect of small doses (≤30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals. METHODS MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added ≤30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE. RESULTS Forty trial comparisons (n = 400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P < 0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P < 0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P = 0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose. CONCLUSIONS Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements.
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Effect of omalizumab use on glucose homeostasis in non-diabetic patients with chronic urticaria.
Falay Gur, T, Savas Erdogan, S, Erdemir, VA, Doğan, B
Cutaneous and ocular toxicology. 2020;(4):348-353
Abstract
PURPOSE In some diabetic patients receiving omalizumab therapy, blood glucose regulation is impaired. However, the effect of omalizumab on glucose homeostasis in non-diabetic patients remains unknown. METHODS The patients were given subcutaneous omalizumab at a dose of 300 mg every four weeks for the treatment of chronic urticaria in this study. Fasting blood glucose, fasting plasma insulin, total cholesterol, triglyceride, and high-density (HDL) and low-density lipoprotein (LDL) were studied before and at the 12th week of treatment. The homeostatic model assessment for insulin resistance (HOMA-IR) was used to determine insulin resistance. RESULTS Forty of the 45 patients included in the study completed 12 weeks of treatment. While fasting blood glucoses (p = 0.011) and HOMA-IR values (p = 0.027) were significantly increased in the 12th week, the increase in fasting insulin level was not significant (p = 0.07). After treatment, 10 patients developed impaired fasting glucose and 13 developed insulin resistance. CONCLUSION The increase in blood glucose levels may be associated with the paradoxically increase of histamine levels in the blood by omalizumab. If this increase cannot be balanced with insulin, patients may develop impaired glucose tolerance and insulin resistance. Therefore, we suggest that patients using omalizumab should be followed up for glucose homeostasis and insulin resistance.
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Effects of ambient particulate matter on fasting blood glucose: A systematic review and meta-analysis.
Ma, R, Zhang, Y, Sun, Z, Xu, D, Li, T
Environmental pollution (Barking, Essex : 1987). 2020;:113589
Abstract
Studies have found that ambient particulate matter (PM) affects fasting blood glucose. However, the results are not consistent. We conducted a systematic review and meta-analysis to determine the relationship between PM with an aerodynamic diameter of 10 μm or less (PM10) and PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) and fasting blood glucose. We searched PubMed, Web of Science, the Wanfang Database and the China National Knowledge Infrastructure up to April 1, 2019. A total of 24 papers were included in the review, and 17 studies with complete or convertible quantitative information were included in the meta-analysis. The studies were divided into groups by PM size fractions (PM10 and PM2.5) and length of exposure. Long-term exposures were based on annual average concentrations, and short-term exposures were those lasting less than 28 days. In the long-term exposure group, fasting blood glucose increased 0.10 mmol/L (95% CI: 0.02, 0.17) per 10 μg/m3 of increased PM10 and 0.23 mmol/L (95% CI: 0.01, 0.45) per 10 μg/m3 of increased PM2.5. In the short-term exposure group, fasting blood glucose increased 0.02 mmol/L (95% CI: -0.01, 0.04) per 10 μg/m3 of increased PM10 and 0.08 mmol/L (95% CI: 0.04, 0.11) per 10 μg/m3 of increased PM2.5. Further prospective studies are needed to explore the relationship between ambient PM exposure and fasting blood glucose.
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Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.
Carter, S, Solomon, TPJ
Frontiers in endocrinology. 2020;:566548
Abstract
BACKGROUND Exercise improves glycemic control but the magnitude, and in some cases, the direction of this effect is variable. Ambient hyperglycemia has been implicated in this exercise response heterogeneity. The current study investigated whether pre-exercise hyperglycemia directly impacts the effect of exercise on glycemic control. METHODS Twelve healthy normal glucose-tolerant males completed four trials in a randomized, crossover design. Each trial consisted of 24-h pre-intervention monitoring, a 7-h intervention, and 24-h post-intervention monitoring. Glycemic control was measured throughout the study by continuous glucose monitoring. The four interventions were no exercise (CON) or 45 min of cycling exercise (70%HRmax) preceded by 3.5 h of either normoglycemia (NG-Ex), steady-state hyperglycemia induced by constant glucose infusion (HG-Ex) or fluctuating glycemia induced by repeated glucose bolus infusions (FG-Ex). RESULTS Physical activity and diet were similar between trials, and energy expenditure during exercise was matched between exercise trials (all P > 0.05). Mean glucose during the 3.5 h ± infusion period was higher in HG-Ex (mean ± SEM; 7.2 ± 0.4 mmol/L) and FG-Ex (7.3 ± 0.3 mmol/L) compared to CON (4.8 ± 0.2 mmol/L) and NG-Ex (5.0 ± 0.2 mmol/L) trials (P < 0.01). Glycemic variability was greatest in FG-Ex (P < 0.01). Following the interventions, the postprandial glucose response (iAUC) was reduced by exercise in NG-Ex compared to CON (321.1 ± 38.6 vs. 445.5 ± 49.7 mmol/L.8h, P < 0.05, d=0.81). This benefit was blunted when exercise was preceded by steady-state (HG-Ex, 425.3 ± 45.7 mmol/L.8h) and fluctuating (FG-Ex, 465.5 ± 39.3 mmol/L.8h) hyperglycemia (both P > 0.05 vs. CON). CONCLUSION Pre-exercise hyperglycemia blunted the glucoregulatory benefits of acute exercise upon postprandial glucose response, suggesting that exposure to hyperglycemia contributes to exercise response heterogeneity. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT03284216.
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Oleuropein-enriched chocolate by extra virgin olive oil blunts hyperglycaemia in diabetic patients: Results from a one-time 2-hour post-prandial cross over study.
Del Ben, M, Nocella, C, Loffredo, L, Bartimoccia, S, Cammisotto, V, Mancinella, M, Angelico, F, Valenti, V, Cavarretta, E, Carnevale, R, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(7):2187-2191
Abstract
BACKGROUND & AIMS Oleuropein, a component of extra virgin olive oil (EVOO), reduces post-prandial glycemia with a mechanism counteracting oxidative stress-mediated incretin down-regulation. In this study we evaluated if the intake of an oleuropein-enriched chocolate could have positive effects on glycaemia and insulin levels in patients with type 2 diabetes mellitus (T2DM) and healthy subjects (HS). METHODS Twenty-five consecutive T2DM patients and 20 HS were recruited. Participants were randomized to receive 40 g oleuropein-enriched chocolate by EVOO or 40 g control chocolate spread in a cross-over design. Serum glucose, insulin, glucagon-like peptide-1 (GLP1), and dipeptidyl-peptidase-4 (DPP4) were measured before and 2 h after chocolate intake. RESULTS In T2DM, the pairwise comparisons showed that intake of oleuropein-enriched chocolate was associated with a significantly less increase of blood glucose compared to control; GLM analysis showed a significant difference for treatments with respect to glucose (p = 0.04), GLP1 (p < 0.001) and DPP-4 activity (p = 0.01). In HS, the pairwise comparisons showed that, after oleuropein-enriched chocolate intake, blood glucose concentration and DPP4 activity did not change; conversely a significant increase was observed for insulin and GLP1. After control chocolate intake, a significant increase for blood glucose, insulin levels and DPP4 activity were observed while GLP1 did not change. CONCLUSION The study shows that using EVOO as source of oleuropein administration of 40 g oleuropein-enriched chocolate is associated with a modest increase or no change of glycemia in T2DM and HS respectively, via an incretin-mediated mechanism.
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An Acute, Placebo-Controlled, Single-Blind, Crossover, Dose-Response, Exploratory Study to Assess the Effects of New Zealand Pine Bark Extract (Enzogenol®) on Glycaemic Responses in Healthy Participants.
Lim, WXJ, Chepulis, L, von Hurst, P, Gammon, CS, Page, RA
Nutrients. 2020;(2)
Abstract
An acute, placebo-controlled, single-blind, crossover, dose-response, exploratory study was designed to investigate the hypoglycaemic effects of New Zealand pine bark extract (Enzogenol®). Twenty-five healthy participants categorised into having a monophasic or complex (biphasic or triphasic) glucose curve shape at the control visit consumed a placebo and Enzogenol® (50 and 400 mg) on three separate occasions before an oral glucose tolerance test (OGTT). In the monophasic group, 50 and 400 mg of Enzogenol® significantly reduced the mean glucose incremental area under the curve (iAUC) compared to control 241.3 ± 20.2 vs. 335.4 ± 34.0 mmol/L·min, p = 0.034 and 249.3 ± 25.4 vs. 353.6 ± 31.5 mmol/L·min, p = 0.012, respectively. The 400 mg dose further reduced the percentage increment of postprandial glucose (%PG) 31.4% ± 7.9% vs. 47.5% ± 8.6%, p = 0.010, glucose peak 7.9 ± 0.3 vs. 8.9 ± 0.3 mmol/L, p = 0.025 and 2h-OGTT postprandial glucose (2hPG) 6.1 ± 0.3 vs. 6.7 ± 0.3 mmol/L, p = 0.027. Glucose iAUC was not significantly different in the complex group, except for reductions in %PG 28.7% ± 8.2% vs. 43.4% ± 5.9%, p = 0.012 after 50 mg dose and 27.7% ± 5.4% vs. 47.3% ± 7.2%, p = 0.025 after 400 mg dose. The results suggest that Enzogenol® may have hypoglycaemic effects in healthy participants, especially those exhibiting monophasic shapes.
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9.
Understanding Metabolic Memory: A Tale of Two Studies.
Miller, RG, Orchard, TJ
Diabetes. 2020;(3):291-299
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Abstract
The results of the Diabetes Control and Complications Trial (DCCT) have given rise to much encouragement in the battle to stave off the complications of type 1 diabetes, showing dramatic declines in the development of severe retinopathy, nephropathy, and neuropathy in those treated intensively compared with conventional therapy. Particularly encouraging has been the continuing difference between the two groups despite both having similar HbA1c (∼8%) since the end of DCCT, when 96% of participants entered the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. This continuing relative benefit has been termed "metabolic memory," which implies altered metabolic regulation. Based on evidence from both the Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset type 1 diabetes and DCCT/EDIC, we show that the metabolic memory effect can be largely explained by lower cumulative glycemic exposure in the intensive therapy group, and, on average, the development of complications increases with greater glycemic exposure, irrespective of whether this results from a high exposure for a short time or a lower exposure for a longer time. Thus, there is no need for a concept like "metabolic memory" to explain these observations. Potential mechanisms explaining the cumulative glycemic effect are also briefly discussed.
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Effects of cultured dairy and nondairy products added to breakfast cereals on blood glucose control, satiation, satiety, and short-term food intake in young women.
Mather, K, Boachie, R, Anini, Y, Panahi, S, Anderson, GH, Luhovyy, BL
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2020;(10):1118-1126
Abstract
Breakfast cereals are often consumed with dairy products or nondairy alternatives; however, the effect of the combination on blood glucose and food intake control is not well investigated. In a randomized, crossover study, 24 healthy women (age: 22.7 ± 2.5 years; body mass index: 22.1 ± 1.5 kg/m2) consumed, to satiation, 1 of 3 treatments: Greek yogurt with granola (150 kcal, 9.2 g protein, 2.6 g fat, 2.0 g dietary fibre, and 21.5 g available carbohydrate/100 g); cultured coconut product with granola (146 kcal, 3.2 g protein, 3.2 g fat, 5.6 g dietary fibre, and 21.9 g available carbohydrate/100 g); or water control. The data were analyzed with repeated-measures ANOVA. The 2 h blood glucose iAUC was 52% lower after the dairy compared with nondairy treatment (P < 0.0001). While there were no differences in food intake between the caloric treatments consumed to satiation, protein intake was 3 times higher and fibre intake was 4 times lower after the dairy compared with nondairy treatment. Both caloric treatments resulted in similar suppression of ad libitum food intake at 2 h (P < 0.003) and subjective appetite over 2 h (P < 0.0001) compared with water. The cumulative food intake over 2 h was lower after water (P < 0.05). The 1.8-fold increase in postprandial insulin after dairy compared with nondairy treatment may explain the reduction in blood glucose without an increase in subsequent energy intake. Novelty Blood glucose in young females is lower after a breakfast with granola in a high-protein cultured dairy than when in a high-fibre nondairy cultured product. Subjective appetite over 2 h and food intake 2 h later was similarly lower after both breakfasts but cumulative intake was higher compared with breakfast skipping.