Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes

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.

Effects of intragastric administration of L-tryptophan on the glycaemic response to a nutrient drink in men with type 2 diabetes — impacts on gastric emptying, glucoregulatory hormones and glucose absorption

Background The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D). Methods Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m2) received, on three separate occasions, 3 g (‘Trp-3’) or 1.5 g (‘Trp-1.5’) tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound. Results Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15–30 min and from t = 30–45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments. Conclusions In people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.

Effect of Treatment of Periodontitis on Incretin Axis in Obese and Nonobese Individuals: A Cohort Study

Context Periodontitis confers an increased risk of developing type 2 diabetes and, in patients with obesity, it might interfere with the incretin axis. The effect of periodontal treatment on glucoregulatory hormones remains unknown. Objective To evaluate the effect of periodontal treatment on incretin axis in obese and lean nondiabetic individuals. Setting King’s College Dental Hospital and Institute, London, UK. Participants and Methods The metabolic profile of obese and normal-body-mass-index individuals affected by periodontitis was studied at baseline, 2, and 6 months after intensive periodontal treatment, by measuring plasma insulin, glucagon, glucagon-like peptide-1(GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) and markers of systemic inflammation and oxidative stress. Main Outcome Measure(s) Circulating levels of incretins and inflammatory markers. Results At baseline, periodontal parameters were worse for obese than nonobese; this was accompanied by higher levels of circulating high-sensitivity C-reactive protein (hs-CRP), insulin, and GLP-1. The response to periodontal treatment was less favorable in the obese group, without significant variations of hs-CRP or malondialdehyde. Glucoregulatory hormones changed differently after treatment: while insulin and glucagon did not vary at 2 and 6 months, GLP-1 and GIP significantly increased at 6 months in both groups. In particular, GLP-1 increased more rapidly in obese participants, while the increase of GIP followed similar trends across visits in both groups. Conclusions Nonsurgical treatment of periodontitis is associated with increased GLP-1 and GIP levels in nonobese and obese patients; changes in GLP-1 were more rapid in obese participants. This might have positive implications for the metabolic risk of these individuals.

Role of Amino Acids in Blood Glucose Changes in Young Adults Consuming Cereal with Milks Varying in Casein and Whey Concentrations and Their Ratio

ABSTRACT Background Increasing the total protein content and reducing the casein to whey ratio in milks consumed with breakfast cereal reduce postprandial blood glucose (BG). Objectives We aimed to explore associations between plasma amino acids (AAs), BG, and glucoregulatory hormones. Methods In this repeated-measures design, 12 healthy adults consumed cereal (58 g) and milks (250 mL) with 3.1 wt% or high 9.3 wt% protein concentrations and with casein to whey ratios of either 80:20 or 40:60. Blood was collected at 0, 30, 60, 120, 140, 170, and 200 min for measurement of the primary outcome, BG, and for the exploratory outcomes such as plasma AA, gastric emptying, insulin (INS), and glucoregulatory hormones. Measures were made prior to and after an ad libitum lunch at 120 min. Exploratory correlations were conducted to determine associations between outcomes. Results Pre-lunch plasma AA groups [total (TAA), essential (EAA), BCAA, and nonessential (NEAA)] were higher after 9.3 wt% than 3.1 wt% milks by 12.7%, 21.4%, 20.9%, and 7.6%, respectively (P ≤ 0.05), while post-lunch AA groups were higher by 10.9%, 19.8%, 18.8%, and 6.0%, respectively (P ≤ 0.05). Except for NEAA, pre-lunch AAs were higher after 40:60 than 80:20 ratio milks by 4.5%, 8.3%, and 9.3% (P ≤ 0.05). When pooled by all treatments, pre-lunch AA groups associated negatively with BG (r/ρ ≥ −0.45, P ≤ 0.05), but post-lunch only TAA and NEAA correlated (r ≥ −0.37, P &lt; 0.05). Pre-lunch BG was inversely associated with Leu, Ile, Lys, Met, Thr, Cys-Cys, Asn, and Gln (r/ρ ≥ −0.46, P ≤ 0.05), but post-lunch, only with Thr, Ala, and Gly (r ≥ −0.50, P ≤ 0.05). Pre-lunch associations between AA groups and INS were not found. Conclusions Protein concentration and the ratio of casein to whey in milks consumed at breakfast with cereal affect plasma AA concentrations and their associations with decreased BG. The decrease in BG could be explained by INS-independent mechanisms. This trial was registered at www.clinicaltrials.gov as NCT02471092.

A ketone monoester drink reduces the glycemic response to an oral glucose challenge in individuals with obesity: a randomized trial

ABSTRACT Background Exogenous ketones make it possible to reach a state of ketosis that may improve metabolic control in humans. Objectives The main objective of this study was to determine whether the ingestion of a ketone monoester (KE) drink before a 2-h oral-glucose-tolerance test (OGTT) would lower blood glucose concentrations. Secondary objectives were to determine the impact of KE on nonesterified fatty acid (NEFA) concentration and glucoregulatory hormones. Methods We conducted a randomized controlled crossover experiment in 15 individuals with obesity (mean ± SD age: 47 ± 10 y; BMI: 34 ± 5 kg/m2). After an overnight fast, participants consumed a KE drink [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate; 0.45 mL/kg body weight] or taste-matched control drink 30 min before completing a 75-g OGTT. Participants and study personnel performing laboratory analyses were blinded to each condition. Results The KE increased d-β-hydroxybutyrate to a maximum of ∼3.4 mM (P < 0.001) during the OGTT. Compared with the control drink, KE reduced glucose (−11%, P = 0.002), NEFA (−21%, P = 0.009), and glucagon-like peptide 1 (−31%, P = 0.001) areas under the curve (AUCs), whereas glucagon AUC increased (+11%, P = 0.030). No differences in triglyceride, C-peptide, and insulin AUCs were observed after the KE drink. Mean arterial blood pressure decreased and heart rate increased after the KE drink (both P < 0.01). Conclusions A KE drink consumed before an OGTT lowered glucose and NEFA AUCs with no increase in circulating insulin. Our results suggest that a single drink of KE may acutely improve metabolic control in individuals with obesity. Future research is warranted to examine whether KE could be used safely to have longer-term effects on metabolic control. This trial was registered at clinicaltrials.gov as NCT03461068.

The Effect of Exercise on Glucoregulatory Hormones: A Countermeasure to Human Aging: Insights from a Comprehensive Review of the Literature

Hormones are secreted in a circadian rhythm, but also follow larger-scale timetables, such as monthly (hormones of the menstrual cycle), seasonal (i.e., winter, summer), and, ultimately, lifespan-related patterns. Several contexts modulate their secretion, such as genetics, lifestyle, environment, diet, and exercise. They play significant roles in human physiology, influencing growth of muscle, bone, and regulating metabolism. Exercise training alters hormone secretion, depending on the frequency, duration, intensity, and mode of training which has an impact on the magnitude of the secretion. However, there remains ambiguity over the effects of exercise training on certain hormones such as glucoregulatory hormones in aging adults. With advancing age, there are many alterations with the endocrine system, which may ultimately alter human physiology. Some recent studies have reported an anti-aging effect of exercise training on the endocrine system and especially cortisol, growth hormone and insulin. As such, this review examines the effects of endurance, interval, resistance and combined training on hormones (i.e., at rest and after) exercise in older individuals. We summarize the influence of age on glucoregulatory hormones, the influence of exercise training, and where possible, examine masters’ athletes’ endocrinological profile.