Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients

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.

Comparison of aspartame- and sugar-sweetened soft drinks on postprandial metabolism

Aim: We compared the impact of artificially- and sugar-sweetened beverages co-ingested with a mixed meal on postprandial fat and carbohydrate oxidation, blood glucose, and plasma insulin and triglyceride concentrations. Methods: Eight college-aged, healthy males completed three randomly assigned trials, which consisted of a mixed macronutrient meal test with 20oz of Diet-Coke (AS), Coca-Cola (NS), or water (CON). One week separated each trial and each participant served as his own control. Resting energy expenditure (REE) via indirect calorimetry, blood pressure, and blood samples were obtained immediately before, 5, 10, 30, 60, 120, and 180 min after meal and beverage ingestion. A two-way (treatment × time) repeated-measures ANOVA was conducted to assess REE, fat and carbohydrate oxidation rates, blood glucose, and plasma insulin and triglyceride concentrations. Results: There was a significant main effect of treatment on total fat oxidation (P = 0.006), fat oxidation was significantly higher after AS (P = 0.006) and CON (P = 0.001) compared to following NS. There was a significant main effect of treatment on total carbohydrate oxidation (P = 0.005), carbohydrate oxidation was significantly lower after AS (P = 0.014) and CON (P = 0.001) compared to following NS. Plasma insulin concentration AUC was significantly lower after AS (P = 0.019) and trended lower in CON (P = 0.054) compared to following NS. Conclusion: Ingestion of a mixed meal with an artificially-sweetened beverage does not impact postprandial metabolism, whereas a sugar-sweetened beverage suppresses fat oxidation and increases carbohydrate oxidation compared to artificially-sweetened beverage and water.

Transorgan Short-Chain Fatty Acid Fluxes in the Fasted and Postprandial State in the Pig

The short-chain fatty acids (SCFAs) acetate, propionate, butyrate, isovalerate, and valerate are end products of intestinal bacterial fermentation and important mediators in the interplay between the intestine and peripheral organs. To unravel the transorgan fluxes and mass balance comparisons of SCFAs, we measured their net fluxes across several organs in a translational pig model. In multi-catheterized conscious pigs (n=12, 25.6 (95% CI [24.2, 26.9]) kg, 8-12 weeks old), SCFA fluxes across portal drained viscera (PDV), liver, kidneys, and hindquarter (muscle compartment) were measured after an overnight fast and in the postprandial state, 4 h after administration of a fiber-free, mixed meal. PDV was the main releasing compartment of acetate, propionate, butyrate, isovalerate, and valerate during fasting and in the postprandial state (all P=0.001). Splanchnic acetate release was high due to the absence of hepatic clearance. All other SCFAs were extensively taken up by the liver (all P<0.05). Even though only 7% [4, 10] (propionate), 42% [23, 60] (butyrate), 26% [12, 39] (isovalerate), and 3% [0.4, 5] (valerate) of PDV release were excreted from the splanchnic area in the fasted state, splanchnic release of all SCFAs was significant (all P≤0.01). Splanchnic propionate, butyrate, isovalerate and valerate release remained low but significant in the postprandial state (all P<0.01). We identified muscle and kidneys as main peripheral SCFA metabolizing organs, taking up the majority of all splanchnically released SCFAs in the fasted state and in the postprandial state. We conclude that the PDV is the main SCFA releasing and the liver the main SCFA metabolizing organ. Splanchnically released SCFAs appear to be important energy substrates to peripheral organs not only in the fasted but also in the postprandial state.

Effect of meal composition and alcohol consumption on postprandial glucose concentration in subjects with type 1 diabetes: a randomized crossover trial

IntroductionMeal composition is known to affect glycemic variability and glucose control in type 1 diabetes. The objective of this work was to evaluate the effect of high carbohydrate meals of different nutritional composition and alcohol on the postprandial glucose response in patients with type 1 diabetes.Research design and methodsTwelve participants were recruited to this randomized crossover trial. Following a 4-week run-in period, participants received a mixed meal on three occasions with the same carbohydrate content but different macronutrient composition: high protein-high fat with alcohol (0.7g/kg body weight, beer), high protein-high fat without alcohol, and low protein-low fat without alcohol at 2-week intervals. Plasma and interstitial glucose, insulin, glucagon, growth hormone, cortisol, alcohol, free fatty acids, lactate, and pH concentrations were measured during 6 hours. A statistical analysis was then carried out to determine significant differences between studies.ResultsSignificantly higher late postprandial glucose was observed in studies with higher content of fats and proteins (p=0.0088). This was associated with lower time in hypoglycemia as compared with the low protein and fat study (p=0.0179), at least partially due to greater glucagon concentration in the same period (p=0.04). Alcohol significantly increased lactate, decreased pH and growth hormone, and maintained free fatty acids suppressed during the late postprandial phase (p<0.001), without significant changes in plasma glucose.ConclusionsOur data suggest that the addition of proteins and fats to carbohydrates increases late postprandial blood glucose. Moreover, alcohol consumption together with a mixed meal has relevant metabolic effects without any increase in the risk of hypoglycemia, at least 6 hours postprandially.Trial registration numberNCT03320993.

Spontanhypoglykämien: Eine diagnostische Herausforderung

Zusammenfassung Anamnese Die Vorstellung einer 59-jährigen Frau erfolgte zur endokrinologischen Abklärung rezidivierender Spontanhypoglykämien. Die Beschwerden waren stets nach Kohlenhydrataufnahme regredient. Aufgrund eines klassischen adrenogenitalen Syndroms erhielt die Patientin seit jungen Jahren eine Substitutionstherapie mit Hydrocortison. Untersuchung Die Patientin präsentierte sich in einem altersentsprechenden Allgemein- und leicht übergewichtigen Ernährungszustand. Der Blutzucker lag zum Aufnahmezeitpunkt bei 87 mg/dl. Weiterhin konnten unter Substitution mit retardiertem Hydrocortison ein unauffälliges Cortisol sowie adrenokortikotropes Hormon (ACTH) nachgewiesen werden. Im Mixed-Meal-Tolerance-Test (MMTT, standardisierter Frühstückstest) zeigte sich keine reaktive Hypoglykämie. Im anschließenden 72-Stunden-Hungerversuch trat nach 36 Stunden eine symptomatische Hypoglykämie auf. Bei einem Blutzucker von 46 mg/dl (Referenzbereich: 74–106) fand sich ein vermindertes Insulin. Auffällig waren jedoch ein niedriges Cortisol sowie ein deutlich erhöhtes ACTH, hinweisend auf eine Unterversorgung mit Hydrocortison zum Zeitpunkt der Hypoglykämie. Therapie und Verlauf Aufgrund der vermuteten therapeutischen Lücke wurde mit der Patientin eine Dosiserhöhung des morgendlichen retardierten Hydrocortisons besprochen. Da dies keinen klinischen Erfolg hatte, wurde die Applikationsform auf morgens und abends geändert. Folgerung Die vorliegende Kasuistik demonstriert, dass nicht nur ein endogener Hyperinsulinismus ursächlich für Spontanhypoglykämien sein kann, sondern ebenfalls eine fehlerhafte Gegenregulation zu symptomatischen Unterzuckerungen führen kann. Der MMTT sowie der 72-Stunden-Hungerversuch sollten zur Diagnostik angewendet werden. Hierbei ist darauf zu achten, dass in der Hypoglykämie eine unmittelbare Hormonanalytik erfolgt. Durch das Verhältnis von Insulin, C-Peptid sowie Proinsulin zum Blutzucker und anhand der Konstellation der kontrainsulinären Hormone wie Cortisol, ACTH, Wachstumshormon, Insulin-like growth factor 1 (IGF-1) sowie der Katecholamine kann eine Aussage über die Ätiologie der Hypoglykämie getroffen werden.

Prolonged Honeymoon Period in a Thai Patient with Adult-Onset Type 1 Diabetes Mellitus

Context. The “honeymoon” phase among people with type 1 diabetes mellitus (T1DM) refers to the period (mostly less than 1 year) in which beta-cells remain functional and are able to produce insulin to maintain good glycemic control shortly following the development of diabetes. This phenomenon is still not completely understood. Previous studies have shown that the absence of diabetic ketoacidosis (DKA) at initial presentation, short duration of symptoms, older age at presentation, and strenuous exercise could be potential factors that influence the honeymoon phase. Objective. To describe a usual case of adult-onset T1DM with prolonged honeymoon period for more than 5 years. Methods. Repeated mixed meal stimulation tests for a period of 6–12 months together with monitoring pancreatic autoantibodies and laboratory data were followed following the onset of diagnosis. Results. We report a 24-year-old Thai patient with T1DM with sustained remission without antidiabetic medication for more than 5 years while maintaining low-carbohydrate intake and regular exercise. Repeated mixed meal stimulation tests for a period of 6–12 months revealed preserved beta-cell functions. Interestingly, repeated pancreatic autoantibodies at 5 years after diagnosis still showed positive anti-GAD, anti-IA2, and anti-ZnT8. Conclusion. Restored beta-cell function with complete insulin withdrawal in new-onset T1DM has been reported in very few cases with some common factors as in our patient (low-carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining the honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.

Plasma GDF15 levels are similar between subjects after bariatric surgery and matched controls and are unaffected by meals

Growth differentiating factor 15 (GDF15) is expressed in the intestine and is one of the most recently identified satiety peptides. The mechanisms controlling its secretion are unclear. The present study investigated whether plasma GDF15 concentrations are meal-related and if potential responses depend on macronutrient type or are affected by previous bariatric surgery. The study included: (1) volunteers ingesting rapidly vs. slowly digested carbohydrates (sucrose vs. isomaltose) (n=10), (2) volunteers who had undergone Roux-en-Y Gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery and unoperated matched controls ingesting a liquid mixed meal (n=9-10 in each group), and (3) individuals with previous RYGB compared with unoperated controls ingesting isocaloric glucose, fat or protein (n=6 in each group). Plasma was collected after an overnight fast and up to 6 h after ingestion (≥12 timepoints). In cohort 1, fasting GDF15 concentrations were ~480 pg/ml. Concentrations after sucrose or isomaltose intake did not differ from baseline (P=0.26-P>0.99) and total area-under-the-curves (tAUCs were similar between groups (P=0.77). In cohort 2, fasting GDF15 concentrations were (pg/ml): RYGB=540±41.4, SG=477±36.4, and controls=590±41.8, with no between-group differences (P=0.73). Concentrations did not increase at any postprandial time point (over all time factor: P=0.10) and tAUCs were similar between groups (P=0.73). In cohort 3, fasting plasma GDF15 was similar among the groups (P>0.99) and neither glucose, fat or protein intake consistently increased the concentrations. In conclusion, we find that plasma GDF15 was not stimulated by meal intake, and that fasting concentrations did not differ between RYGB, SG and BMI-matched controls when investigated during the weight stable phase after RYGB and SG.