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Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients.
Göbl, C, Morettini, M, Salvatori, B, Alsalim, W, Kahleova, H, Ahrén, B, Tura, A
Nutrients. 2022;(2)
Abstract
BACKGROUND glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. METHODS thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants' cohort. RESULTS in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. CONCLUSIONS glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.
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Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes.
Harray, AJ, Binkowski, S, Keating, BL, Horowitz, M, Standfield, S, Smith, G, Paramalingam, N, Jones, T, King, BR, Smart, CEM, et al
The Journal of clinical endocrinology and metabolism. 2022;(1):e205-e213
Abstract
CONTEXT Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. OBJECTIVE Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. METHODS 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. RESULTS Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. CONCLUSION The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.
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Impact of isoenergetic intake of irregular meal patterns on thermogenesis, glucose metabolism, and appetite: a randomized controlled trial.
Alhussain, MH, Macdonald, IA, Taylor, MA
The American journal of clinical nutrition. 2022;(1):284-297
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Abstract
BACKGROUND Evidence is emerging that interdaily meal pattern variability potentially affects response such as thermic effect of food (TEF), macronutrient metabolism, and appetite. OBJECTIVES To investigate the effect of irregular meal pattern on TEF, glucose, insulin, lipid profile, and appetite regulation in women who are overweight or with obesity and confirmed insulin resistance. DESIGN In a randomized crossover trial, 9 women [mean ± SD BMI (in kg/m2): 33.3 ± 3.1] with confirmed insulin resistance consumed a regular (14 d; 6 meals/d) and an irregular (14 d; 3-9 meals/d) meal pattern separated by a 14-d washout interval. Identical foods were provided during the interventions, and at the start and end of each meal pattern, participants attended the laboratory after an overnight fast. Energy expenditure, glucose, insulin, lipids, adiponectin, leptin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin were measured at baseline and for 3 h after consumption of a test drink, after which an ad libitum test meal was offered. Subjective appetite ratings were recorded before and after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 7 consecutive days during each intervention. RESULTS TEF (over 3 h) was significantly lower postirregular intervention compared with postregular (97.7 ± 19.2 kJ*3 h in postregular visit and 76.7 ± 35.2 kJ*3 h in postirregular visit, paired t test, P = 0.048). Differences in HOMA-IR between the 2 interventions (3.3 ± 1.7 and 3.6 ± 1.6 in postregular and postirregular meal pattern, respectively) were not significant. Net incremental AUC for GLP-1 concentrations (over 3 h) for the postregular meal pattern were higher (864.9 ± 456.1 pmol/L*3 h) than the postirregular meal pattern (487.6 ± 271.7 pmol/L*3 h, paired t test, P = 0.005). CONCLUSIONS Following a 14-d period of an irregular meal pattern, TEF was significantly less than following a regular meal pattern, potentially compromising weight management if sustained long term. This study was registered at www.clinicaltrials.gov as NCT02582606.
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Impact of food processing on postprandial glycaemic and appetite responses in healthy adults: a randomized, controlled trial.
Hafiz, MS, Campbell, MD, Orsi, NM, Mappa, G, Orfila, C, Boesch, C
Food & function. 2022;(3):1280-1290
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Abstract
Chickpeas are among the lowest glycaemic index carbohydrate foods eliciting protracted digestion and enhanced satiety responses. In vitro studies suggest that mechanical processing of chickpeas significantly increases starch digestion. However, there is little evidence regarding the impact of processing on postprandial glycaemic response in response to chickpea intake in vivo. Therefore, the aim of this study was to determine the effect of mechanical processing on postprandial interstitial glycaemic and satiety responses in humans. In a randomised crossover design, thirteen normoglycaemic adults attended 4 separate laboratory visits following an overnight fast. On each occasion, one of four test meals, matched for available carbohydrate content and consisting of different physical forms of chickpeas (whole, puree, and pasta) or control (mashed potato), was administered followed by a subsequent standardised lunch meal. Continuous glucose monitoring captured interstitial glucose responses, accompanied by periodic venous blood samples for retrospective analysis of C-peptide, glucagon like peptide-1 (GLP-1), ghrelin, leptin, resistin, and cortisol. Subjective appetite responses were measured by Visual Analogue Scale (VAS). Postprandial glycaemic responses were comparable between chickpea treatments albeit significantly lower than the control (p < 0.001). Similarly, all chickpea treatments elicited significantly lower C-peptide and GLP-1 responses compared to the control (p < 0.05), accompanied by enhanced subjective satiety responses (p < 0.05), whilst no significant differences in satiety hormones were detected among different intervention groups (p > 0.05). Chickpea consumption elicits low postprandial glycaemic responses and enhanced subjective satiety responses irrespective of processing methods.
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The relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio required to maintain glycaemia is non-linear in young people with type 1 diabetes: A randomized crossover trial.
Cordon, NM, Smart, CEM, Smith, GJ, Davis, EA, Jones, TW, Seckold, R, Burckhardt, MA, King, BR
Diabetic medicine : a journal of the British Diabetic Association. 2022;(2):e14675
Abstract
OBJECTIVE To determine if the relationship between meal carbohydrate quantity and the insulin to carbohydrate ratio (ICR) required to maintain glycaemia is linear in people with type 1 diabetes. METHODS We used an open labelled randomized four-arm cross-over study design. Participants (N = 31) aged 12-27 years, HbA1c ≤ 64 mmol/mol (8.0%) received insulin doses based on the individual's ICR and the study breakfast carbohydrate quantity and then consumed four breakfasts containing 20, 50, 100 and 150 g of carbohydrate over four consecutive days in randomized order. The breakfast fat and protein percentages were standardized. Postprandial glycaemia was assessed by 5 h continuous glucose monitoring. The primary outcome was percent time in range (TIR) and secondary outcomes included hypoglycaemia, glucose excursion and incremental area under the curve. Statistical analysis included linear mixed modelling and Wilcoxon signed rank tests. RESULTS The 20 g carbohydrate breakfast had the largest proportion of TIR (0.74 ± 0.29 p < 0.04). Hypoglycaemia was more frequent in the 50 g (n = 13, 42%) and 100 g (n = 15, 50%) breakfasts compared to the 20 g (n = 6, 20%) and 150 g (n = 7, 26%) breakfasts (p < 0.029). The 150 g breakfast glucose excursion pattern was different from the smaller breakfasts with the lowest glucose excursion 0-2 h and the highest excursion from 3.5 to 5 h. CONCLUSIONS A non-linear relationship between insulin requirement and breakfast carbohydrate content was observed, suggesting that strengthened ICRs are needed for meals with ≤20 and ≥150 g of carbohydrate. Meals with ≥150 g of carbohydrate may benefit from dual wave bolusing.
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Safflower (Carthamus tinctorius L.) oil could improve abdominal obesity, blood pressure, and insulin resistance in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial.
Ruyvaran, M, Zamani, A, Mohamadian, A, Zarshenas, MM, Eftekhari, MH, Pourahmad, S, Abarghooei, EF, Akbari, A, Nimrouzi, M
Journal of ethnopharmacology. 2022;:114590
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Carthamus tinctorius L. (Safflower) has been widely recommended to treat metabolic disorders in traditional herbal medicine in Persia, China, Korea, Japan, and other East-Asian countries. The anti-hypercholesterolemic and antioxidant effects of this plant have been well documented, but its protective effects against Metabolic Syndrome (MetS) have not been fully illustrated. AIM OF THE STUDY The present study aimed to evaluate the effects of safflower oil on MetS risk factors. MATERIALS AND METHODS In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with MetS were administered either divided 8 g safflower oil or placebo daily for 12 weeks. All patients were advised to follow their previous diets and physical activities. RESULTS Safflower oil resulted in a significant reduction in waist circumference (-2.42 ± 3.24 vs. 0.97 ± 2.53, p<0.001), systolic blood pressure (-8.80 ± 9.77 vs. -2.26 ± 8.56, p = 0.021), diastolic blood pressure (-3.53 ± 7.52 vs. -0.70 ± 6.21, p = 0.041), fasting blood sugar (-5.03 ± 10.62 vs. 2.94 ± 7.57, p = 0.003), and insulin resistance (-0.59 ± 1.43 vs. 0.50 ± 1, p = 0.012), but an increase in adiponectin level (0.38 ± 0.99 vs. -0.09 ± 0.81, p = 0.042) in the treatment group in comparison to the placebo group. The results revealed a direct relationship between leptin level and Body Mass Index (BMI) in both groups (p<0.001). In addition, increase in BMI resulted in a non-significant decrease in adiponectin level in both groups. Moreover, no significant difference was observed between the two groups regarding lipid profiles, leptin serum level, serum creatinine concentration, and other outcomes. CONCLUSION Safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with MetS.
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A Comparative Study of Health Efficacy Indicators in Subjects with T2DM Applying Power Cycling to 12 Weeks of Low-Volume High-Intensity Interval Training and Moderate-Intensity Continuous Training.
Li, J, Cheng, W, Ma, H
Journal of diabetes research. 2022;:9273830
Abstract
This study is aimed at comparing the effects of different exercise intensities, namely, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on body composition, heart and lung fitness, and blood glucose, and blood pressure indices in patients with type 2 diabetes mellitus (T2DM), using power cycling. A total of 96 T2DM volunteers who met the inclusion criteria were recruited from a hospital in Yangpu, Shanghai. Based on the blood index data of their medical examination results which comprised blood pressure, fasting blood glucose, hemoglobin A1c (HbA1c), and insulin, 37 volunteers were included in the study. Exercise prescription was determined based on T2DM exercise guidelines combined with medical diagnosis and exercise test results, and the patients were randomly assigned to three groups: HIIT group, MICT group, and control (CON) group. HIIT involved one-minute power cycling (80%-95% maximal oxygen uptake (VO2max)), one-minute passive or active rest (25%-30% VO2max), and two-minute rounds of eight groups. MICT required the use of a power bike for 30 minutes of continuous training (50%-70% VO2max) five times a week. The CON group was introduced to relevant medicine, exercise, and nutrition knowledge. The exercise interventions were completed under the supervision of an exercise instructor and hospital doctors. The same indicators were measured after 12 weeks of intervention, and the results of the two tests within and between groups were analyzed for comparison. The weight index of the MICT intervention showed statistically significant within-group differences (difference = 3.52, 95% CI = 2.11-4.92, p = 0.001 < 0.01); group differences for the MICT and CON groups were also statistically significant (difference = 3.52 ± 2.09, Cd1 = -0.39 ± 1.25, p = 0.004 < 0.01). Body mass index (BMI) analysis revealed that the overall means of BMI indicators were not statistically different between groups (F = 0.369, p = 0.694 > 0.05) and the before and after values of the MICT and CON (difference = -1.30 ± 0.79, Cd1 = -0.18 ± 0.45, p = 0.001 < 0.01). No statistically significant difference was observed in the overall mean VO2max index between the groups after the 12-week intervention (F = 2.51, p = 0.100 > 0.05). A statistically significant difference was found in the overall means of the data between the two groups (difference = 0.32, 95% CI = 0.23-0.40, p = 0.001 < 0.01). Analysis of fasting blood glucose (FBG) indicators revealed statistically significant differences between the MICT and control groups (p = 0.028 < 0.05). Analysis of HbA1c and fasting insulin (FI) indicators revealed no statistically significant difference in the overall HbA1c index after the 12-week exercise intervention (F = 0.523, p = 0.598 > 0.05), and the overall difference before and after the experiment between the groups was statistically significant (F = 6.13, p = 0.006 < 0.01). No statistically significant difference was found in the FI index overall after the 12-week exercise intervention (F = 2.50, p = 0.1 > 0.05). Analysis of systolic blood pressure (SBP) revealed statistically significant difference before and after the HIIT and CON interventions (Hd7 = -1.10 ± 1.79, Cd7 = 1.2 ± 1.31, p = 0.018 < 0.05) and statistically significant difference before and after the MICT and CON interventions (Md7 = -0.99 ± 0.91, Cd7 = 1.40 ± 1.78, p = 0.02 < 0.05). The diastolic blood pressure (DBP) revealed no statistically significant within-group differences before and after. Exercise interventions applying both low-volume HIIT and MICT, with both intensity exercises designed for power cycling, improved health-related indicators in the participants; low-volume HIIT had more time advantage. The current experiment compared HIIT with MICT in a safe manner: 50% of the exercise time produced similar benefits and advantages in the two indicators of VO2max and FI. However, MICT was superior to HIIT in the two indicators of body weight (weight) and BMI. The effect of power cycling on FI has the advantages of both aerobic and resistance exercise, which may optimize the type, intensity, and time of exercise prescription according to the individual or the type of exercise program. Our results provide a reference for the personalization of exercise prescription for patients with T2DM.
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Effect of Mori ramulus on the postprandial blood glucose levels and inflammatory responses of healthy subjects subjected to an oral high-fat/sucrose challenge: A double-blind, randomized, crossover clinical trial.
Park, SY, Kwon, O, Kim, JY
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112552
Abstract
Blood glucose is inadequately controlled in diabetes mellitus, causing various inflammation-related complications. This study aimed to investigate responses to an oral sucrose/lipid challenge in the context of glucose metabolism after consumption of Mori ramulus (MR) extract. In this study on healthy subjects, the optimal dose and safety of MR were confirmed in a preliminary pilot trial (n = 24), meanwhile, blood glucose, insulin, and inflammatory marker levels were detected via an oral sucrose/lipid tolerance test in the main trial (n = 36). In the main study, the blood glucose response was significantly decreased after 240 min in the MR group. Compared to the placebo group, the treatment group exhibited plasma insulin levels that were significantly increased at 120 min and decreased at 240 min. In conclusion, a single MR extract dose protects against inflammation induced by high-fat/sugar to maintain normal insulin secretion and thus helps to maintain postprandial blood glucose levels via an inflammatory mechanism.
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Single Ingestion of Trehalose Enhances Prolonged Exercise Performance by Effective Use of Glucose and Lipid in Healthy Men.
Hamada, N, Wadazumi, T, Hirata, Y, Kuriyama, M, Watanabe, K, Watanabe, H, Hongu, N, Arai, N
Nutrients. 2021;(5)
Abstract
Trehalose increases blood glucose levels slowly and induces a slight insulin response. The present study aimed to study the effect of trehalose on prolonged exercise performance. The participants were 12 healthy men (age: 21.3 ± 0.9 y). After an overnight fast (12 h), they first exercised with a constant load (intensity: 40% V˙O2peak) for 60 min using a bicycle ergometer. They continued to exercise with a constant load (40% V˙O2peak) for 30 min between four sets of the 30-s Wingate test. After the 1st set, each participant ingested 500 mL water (control), 8% glucose, or 8% trehalose in three trials. These three trials were at least one week apart and were conducted in a double-blind and randomized crossover manner. Blood was collected for seven biochemical parameters at 12 time points during the experiment. The area under the curve of adrenaline after ingestion of trehalose was significantly lower than that for water and tended to be lower than that for glucose in the later stage of the exercise. Lower secretion of adrenaline after a single dose of 8% trehalose during prolonged exercise reflected the preservation of carbohydrates in the body in the later stage of the exercise. In conclusion, a single ingestion of trehalose helped to maintain prolonged exercise performance.
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Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial.
Bharmal, SH, Cho, J, Alarcon Ramos, GC, Ko, J, Cameron-Smith, D, Petrov, MS
The Journal of nutrition. 2021;(4):921-929
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BACKGROUND The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown. OBJECTIVES The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides. METHODS This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time. RESULTS Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1. CONCLUSIONS Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.