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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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Metformin action over gut microbiota is related to weight and glycemic control in gestational diabetes mellitus: A randomized trial.
Molina-Vega, M, Picón-César, MJ, Gutiérrez-Repiso, C, Fernández-Valero, A, Lima-Rubio, F, González-Romero, S, Moreno-Indias, I, Tinahones, FJ
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112465
Abstract
BACKGROUND Metformin, which is known to produce profound changes in gut microbiota, is being increasingly used in gestational diabetes mellitus (GDM). The aim of this study was to elucidate the differences in gut microbiota composition and function in women with GDM treated with metformin compared to those treated with insulin. METHODS From May to December 2018, 58 women with GDM were randomized to receive insulin (INS; n = 28) or metformin (MET; n = 30) at the University Hospital Virgen de la Victoria, Málaga, Spain. Basal visits, with at least 1 follow-up visit and prepartum visit, were performed. At the basal and prepartum visits, blood and stool samples were collected. The gut microbiota profile was determined through 16S rRNA analysis. RESULTS Compared to INS, women on MET presented a lower mean postprandial glycemia and a lower increase in weight and body mass index (BMI). Firmicutes and Peptostreptococcaceae abundance declined, while Proteobacteria and Enterobacteriaceae abundance increased in the MET group. We found inverse correlations between changes in the abundance of Proteobacteria and mean postprandial glycemia (p = 0.023), as well as between Enterobacteriaceae and a rise in BMI and weight gain (p = 0.031 and p = 0.036, respectively). Regarding the metabolic profile of gut microbiota, predicted metabolic pathways related to propionate degradation and ubiquinol biosynthesis predominated in the MET group. CONCLUSION Metformin in GDM affects the composition and metabolic profile of gut microbiota. These changes could mediate, at least in part, its clinical effects. Studies designed to assess how these changes influence metabolic control during and after pregnancy are necessary.
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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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Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT).
Thom, G, Messow, CM, Leslie, WS, Barnes, AC, Brosnahan, N, McCombie, L, Al-Mrabeh, A, Zhyzhneuskaya, S, Welsh, P, Sattar, N, et al
Diabetic medicine : a journal of the British Diabetic Association. 2021;(8):e14395
Abstract
AIM: To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial). METHODS Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m2 , and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA1c <48 mmol/mol [<6.5%], without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m2 ) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss. RESULTS Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA1c was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non-remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C-peptide and diabetes duration did not predict remission. CONCLUSIONS Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target.
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Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial.
Yang, L, Liang, H, Liu, X, Wang, X, Cheng, Y, Zhao, Y, Liu, L, Huang, G, Wang, X, Zhou, Z
The Journal of clinical endocrinology and metabolism. 2021;(4):e1529-e1541
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CONTEXT The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. OBJECTIVE To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin. DESIGN AND SETTING A randomized controlled trial at the Second Xiangya Hospital. METHODS Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months. MAIN OUTCOME MEASURES Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP - FCP), and updated homeostatic model assessment of β-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals. RESULTS During the 24-month follow-up, there were no significant changes in β-cell function in the SITA group, whereas the levels of 2hCP and △CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P < .001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P < .01 vs baseline), which were higher than in the CONT group. CONCLUSION Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.
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Is the stepping-down approach a better option than multiple daily injections in obese patients with poorly controlled Type 2 diabetes on advanced insulin therapy?
Naing, S, Ramesh, G, Garcha, J, Poliyedath, A, Khandelwal, S, Mills, PK
Endocrinology, diabetes & metabolism. 2021;(2):e00204
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AIM: To determine whether de-escalating from advanced insulin therapy (AIT) to the combined use of metformin, an SGLT2 inhibitor, a GLP1 receptor agonist and basal insulin is the better option than multiple daily insulin injections (MDI) in obese patients with poorly controlled T2DM. METHODS This was a 16-week, prospective, randomized, controlled trial. Twenty-two obese patients with T2DM on AIT were randomized to intervention (step-down) or control (MDI) group. In the intervention group, all prandial insulin injections were discontinued, but the patient remained on basal insulin and metformin, to which an SGLT2i and a GLP1 RA were added. In the control group, the patient remained on MDI. RESULTS Compared to control group (n = 8), A1c was significantly lower at week 4 (9.54% vs 8.25%; p = .0088) and week 16 (9.7% vs 7.31%; p < .001) in intervention group (n = 10). In intervention group, compared to baseline, there was a significant decrease in weight (-16.38 pounds; p = .003), BMI (-3.06; p < .001), LDL cholesterol (-15.7 mg/dl; p = .0378), total cholesterol (-18.5 mg/dl; p = .0386), total daily insulin dose (-57.3 units; p < .001) and a significant improvement in DM-SAT patient satisfaction 0-100 scores: total score (+45.3; p < .001) and subscale scores (Convenience + 35.28, p = .019; Lifestyle + 35.8, p = .0052; Medical control + 51.3, p < .001; Wellbeing + 47.2, p = .0091) at week 16. CONCLUSION De-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin in obese patients with poorly controlled T2DM on MDI resulted in significant improvement in glycaemic control, weight loss and significantly higher patient satisfaction. This stepping-down approach may be the better option than continuing MDI in these patients.
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The effect of a 6-month ketogenic medium-chain triglyceride supplement on plasma cardiometabolic and inflammatory markers in mild cognitive impairment.
Myette-Côté, É, St-Pierre, V, Beaulieu, S, Castellano, CA, Fortier, M, Plourde, M, Bocti, C, Fulop, T, Cunnane, SC
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102236
Abstract
INTRODUCTION Mild cognitive impairment (MCI) is often accompanied by metabolic abnormalities and inflammation that might play a role in the development of cognitive impairment. The use of ketogenic medium-chain triglycerides (kMCT) to improve cognition in this population has shown promising results but remains controversial because of the potentially detrimental effect of elevated intake of saturated fatty acids on cardiovascular (CV) health and perhaps inflammatory processes. The primary aim of this secondary data analysis report is to describe changes in cardiometabolic markers and peripheral inflammation during a 6-month kMCT intervention in MCI. METHODS Thirty-nine participants with MCI completed the intervention of 30 g/day of either a kMCT drink or calorie-matched placebo (high-oleic acid) for 6 months. Plasma concentrations of cardiometabolic and inflammatory markers were collected before (fasting state) and after the intervention (2 h following the last drink). RESULTS A mixed model ANOVA analysis revealed a time by group interaction for ketones (P < 0.001), plasma 8:0 and 10:0 acids (both P < 0.001) and IL-8 (P = 0.002) with follow up comparison revealing a significant increase in the kMCT group (+48%, P = 0.005), (+3,800 and +4,900%, both P < 0.001) and (+147%, P < 0.001) respectively. A main effect of time was observed for insulin (P = 0.004), triglycerides (P = 0.011) and non-esterified fatty acids (P = 0.036). CONCLUSION Under these study conditions, 30 g/d of kMCT taken for six months and up to 2-hour before post-intervention testing had minimal effect on an extensive profile of circulating cardiometabolic and inflammatory markers as compared to a placebo calorie-matched drink. Our results support the safety kMCT supplementation in individuals with MCI. The clinical significance of the observed increase in circulating IL-8 levels is presently unknown and awaits future studies.
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The comparison of two mealtime insulin dosing algorithms for high and low glycaemic index meals in adolescents with type 1 diabetes.
Erdal, B, Caferoglu, Z, Hatipoglu, N
Diabetic medicine : a journal of the British Diabetic Association. 2021;(3):e14444
Abstract
AIMS: Postprandial glycaemic variability carries on being a clinical challenge in optimizing glucose control in type 1 diabetes. The aim of this study was to compare the postprandial glycaemic effects of carbohydrate counting and food insulin index algorithms following the consumption of protein-rich, high-fat meals with different glycaemic index (GI) in adolescents with type 1 diabetes. METHODS A randomized, single-blind and crossover trial included 15 adolescents aged 14-18 years with type 1 diabetes. Participants consumed two different test meals with similar energy, macronutrients and food insulin index but the approximately twofold difference in GI, in random order on four consecutive mornings at their home. Insulin dose for high- and low-GI test meals was determined by using the carbohydrate counting and food insulin index algorithms. Four-hour postprandial glycaemia was assessed by the continuous glucose monitoring system. RESULTS Compared with carbohydrate counting, the food insulin index algorithm significantly decreased peak glucose excursion (-57%, p = 0.02), incremental area under the curve (-65%, p = 0.02) and coefficient variation of blood glucose (-37%, p = 0.03) in the high-GI meal, though there was no difference between the two algorithms in the low-GI meal. The occurrence of hypoglycaemia did not significantly differ between insulin dosing algorithms for the high-GI (p = 0.58) and low-GI (p = 0.20) meals. CONCLUSIONS The food insulin index algorithm may be beneficial for postprandial glycaemic control after the consumption of high-GI meals in adolescents with type 1 diabetes.
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Insulin/IGF-1 Signaling Is Downregulated in Barrett's Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial.
Arcidiacono, D, Zaramella, A, Fabris, F, Sánchez-Rodríguez, R, Nucci, D, Fassan, M, Nardi, M, Benna, C, Cristofori, C, Morbin, T, et al
Nutrients. 2021;(10)
Abstract
Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett's esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions.