Ketone production and excretion even during mild hyperglycemia and the impact of sodium-glucose co-transporter inhibition in type 1 diabetes.

AIMS: We aimed to determine if ketone production and excretion are increased even at mild fasting hyperglycemia in type 1 diabetes (T1D) and if these are modified by ketoacidosis risk factors, including sodium-glucose co-transporter inhibition (SGLTi) and female sex. METHODS: In secondary analysis of an 8-week single-arm open-label trial of empagliflozin (NCT01392560) we evaluated ketone concentrations during extended fasting and clamped euglycemia (4-6 mmol/L) and mild hyperglycemia (9-11 mmol/L) prior to and after treatment. Plasma and urine beta-hydroxybutyrate (BHB) concentrations and fractional excretion were analyzed by metabolomic analysis. RESULTS: Forty participants (50 % female), aged 24 ± 5 years, HbA1c 8.0 ± 0.9 % (64 ± 0.08 mmol/mol) with T1D duration of 17.5 ± 7 years, were studied. Increased BHB production even during mild hyperglycemia (median urine 6.3[3.5-13.6] vs. 3.5[2.2-7.0] µmol/mmol creatinine during euglycemia, p < 0.001) was compensated by increased fractional excretion (0.9 % [0.3-1.6] vs. 0.4 % [0.2-0.9], p < 0.001). SGLTi increased production and attenuated the increased BHB fractional excretion (decreased to 0.3 % during mild hyperglycemia, p < 0.001), resulting in higher plasma concentrations (increased to 0.21 [0.05-0.40] mmol/L, p < 0.001), particularly in females (interaction p < 0.001). CONCLUSIONS: Even mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion, in T1D. However, SGLTi exaggerates production and partially reduces compensatory excretion, particularly in women.

Minimal Effective Dose of Beans Required to Elicit a Significantly Lower Glycemic Response Than Commonly Consumed Starchy Foods: Predictions Based on In Vitro Digestion and Carbohydrate Analysis.

Beans elicit lower glycemic responses (GRs) than other starchy foods, but the minimum effective dose (MED) to reduce GR is unknown. We sought to determine the MED of beans compared to common starchy foods. Overnight-fasted healthy volunteers consumed »c (phase 1, n = 24) or ½c (phase 2, n = 18) of black, cranberry, great northern, kidney, navy and pinto beans and corn, rice, pasta and potato (controls), with blood glucose measured before and for 2 h after eating. GRs (incremental areas under the curves, iAUCs) after beans were consumed were compared to those of controls by ANOVA followed by Dunnett's test. To qualify for MED, beans had to elicit an effective reduction in GR, defined as a statistically significant reduction in iAUC of ≥20% (i.e., a relative glycemic response, RGR, ≤80). Outcomes from in vitro digestion were compared with in vivo RGR. Both doses of all six beans effectively reduced GR versus all four starchy controls, except for »c and ½c cranberry and pinto vs. corn, »c great northern and navy vs. corn and »c navy and pinto vs. potato. MED criteria were met for 18 comparisons of the »c servings, with four of the remaining six met by the ½c servings. The overall mean ± SEM RGR vs. controls was similar for the »c and ½c servings: 53 ± 4% and 56 ± 3%, respectively. By multiple regression analysis, RGR = 23.3 × RDS + 8.3 × SDS - 20.1 × RS + 39.5 × AS - 108.2 (rapidly digested starch, p < 0.001; slowly digested starch, p = 0.054; resistant starch, p = 0.18; available sugars, p = 0.005; model r = 0.98, p = 0.001). RGR correlated with in vitro glucose release (r = 0.92, p < 0.001). The MED of beans is » cup. For n = 30 comparisons (n = 24 beans vs. controls, n = 6 controls vs. each other), an effective reduction in GR was predicted from in vitro carbohydrate analysis with 86% sensitivity and 100% specificity.

Fructose-containing food sources and blood pressure: A systematic review and meta-analysis of controlled feeding trials.

Whether food source or energy mediates the effect of fructose-containing sugars on blood pressure (BP) is unclear. We conducted a systematic review and meta-analysis of the effect of different food sources of fructose-containing sugars at different levels of energy control on BP. We searched MEDLINE, Embase and the Cochrane Library through June 2021 for controlled trials ≥7-days. We prespecified 4 trial designs: substitution (energy matched substitution of sugars); addition (excess energy from sugars added); subtraction (excess energy from sugars subtracted); and ad libitum (energy from sugars freely replaced). Outcomes were systolic and diastolic BP. Independent reviewers extracted data. GRADE assessed the certainty of evidence. We included 93 reports (147 trial comparisons, N = 5,213) assessing 12 different food sources across 4 energy control levels in adults with and without hypertension or at risk for hypertension. Total fructose-containing sugars had no effect in substitution, subtraction, or ad libitum trials but decreased systolic and diastolic BP in addition trials (P<0.05). There was evidence of interaction/influence by food source: fruit and 100% fruit juice decreased and mixed sources (with sugar-sweetened beverages [SSBs]) increased BP in addition trials and the removal of SSBs (linear dose response gradient) and mixed sources (with SSBs) decreased BP in subtraction trials. The certainty of evidence was generally moderate. Food source and energy control appear to mediate the effect of fructose-containing sugars on BP. The evidence provides a good indication that fruit and 100% fruit juice at low doses (up to or less than the public health threshold of ~10% E) lead to small, but important reductions in BP, while the addition of excess energy of mixed sources (with SSBs) at high doses (up to 23%) leads to moderate increases and their removal or the removal of SSBs alone (up to ~20% E) leads to small, but important decreases in BP in adults with and without hypertension or at risk for hypertension. Trial registration: Clinicaltrials.gov: NCT02716870.

Cross-linked phosphorylated RS4 wheat starch reduces glucose and insulin responses after 3 days of pre-feeding in healthy adults: an acute, double-blind, randomized controlled clinical trial.

When this project was designed, there was no evidence that adding resistant starch to available carbohydrate (avCHO) reduced glycaemic and insulinaemic responses (GIR). We compared GIR elicited by a cookie containing cross-linked phosphorylated RS4 wheat starch (Fibersym®) (RS4XL) versus an avCHO-matched control-cookie (CC) after n = 15 adults had consumed RS4XL or CC daily for 3-days using a double-blind, randomised, cross-over design. The difference in glucose iAUC over 0-2 h (primary endpoint) (mmol × min/L) after RS4XL, (mean ± SEM) 106 ± 16, versus CC, 124 ± 16, was not significant (p = 0.087). However, RS4XL reduced 0-90 min glucose iAUC (72 ± 9 vs 87 ± 9, p = 0.022), peak glucose concentration (6.05 ± 0.36 vs 6.57 ± 0.31 mmol/L, p = 0.017) and 0-2 h insulin iAUC (189 ± 21 vs 246 ± 24 nmol × h/L, p = 0.020). These results show that RS4XL reduced postprandial glycaemic and insulinaemic responses when added to avCHO, but do not prove that the products of its colonic fermentation are required for this effect.

The importance of molecular weight in determining the minimum dose of oat ß-glucan required to reduce the glycaemic response in healthy subjects without diabetes: a systematic review and meta-regression analysis.

To determine the minimum amount of oat ß-glucan (OBG) required to reduce glycaemic responses (MinDose), we conducted a systematic review and meta-regression analysis of acute, crossover, single-meal feeding trials that examined the effects of adding OBG or oat bran to a carbohydrate-containing test-meal versus a control test-meal containing an equivalent amount of available-carbohydrate (avCHO) from the same or similar source. Medline, Embase, and Cochrane Library were searched up to 18 August 2021. The primary outcome was glucose incremental-area-under-the-curve (iAUC). Secondary outcomes included insulin iAUC, and glucose and insulin incremental peak-rise (iPeak). Two independent reviewers extracted data. Results were expressed as ratio-of-means (RoM) with 95% confidence intervals (CIs). Linear associations were assessed by random effects meta-regression. MinDose was defined as the dose at which the upper 95% CI of the regression line cut the line of no effect (i.e., RoM = 1). Fifty-nine comparisons (n = 340) were included; 57 in healthy subjects without diabetes and two in subjects with diabetes; 24 high-MW (>1000 kg/mol), 22 medium-MW (300-1,000 kg/mol), and 13 low-MW (<300 kg/mol). In healthy subjects without diabetes the associations between OBG dose and glucose iAUC and iPeak were linear (non-linear p value >0.05). MinDoses for glucose iAUC for high-MW, medium-MW and low-MW OBG, respectively, were estimated to be 0.2 g, 2.2 g and 3.2 g per 30 g avCHO; MinDoses for glucose iPeak were less than those for iAUC. Insufficient data were available to assess MinDose for insulin, however, there was no evidence of a disproportionate increase in insulin. More high-quality trials are needed to establish MinDose in individuals with diabetes.

Effect of Important Food Sources of Fructose-Containing Sugars on Inflammatory Biomarkers: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Fructose-containing sugars as sugar-sweetened beverages (SSBs) may increase inflammatory biomarkers. Whether this effect is mediated by the food matrix at different levels of energy is unknown. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials on the effect of different food sources of fructose-containing sugars on inflammatory markers at different levels of energy control. METHODS: MEDLINE, Embase, and the Cochrane Library were searched through March 2022 for controlled feeding trials ≥ 7 days. Four trial designs were prespecified by energy control: substitution (energy matched replacement of sugars); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced). The primary outcome was C-reactive protein (CRP). Secondary outcomes were tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Independent reviewers extracted data and assessed risk of bias. GRADE assessed certainty of evidence. RESULTS: We identified 64 controlled trials (91 trial comparisons, n = 4094) assessing 12 food sources (SSB; sweetened dairy; sweetened dairy alternative [soy]; 100% fruit juice; fruit; dried fruit; mixed fruit forms; sweetened cereal grains and bars; sweets and desserts; added nutritive [caloric] sweetener; mixed sources [with SSBs]; and mixed sources [without SSBs]) at 4 levels of energy control over a median 6-weeks in predominantly healthy mixed weight or overweight/obese adults. Total fructose-containing sugars decreased CRP in addition trials and had no effect in substitution, subtraction or ad libitum trials. No effect was observed on other outcomes at any level of energy control. There was evidence of interaction/influence by food source: substitution trials (sweetened dairy alternative (soy) and 100% fruit juice decreased, and mixed sources (with SSBs) increased CRP); and addition trials (fruit decreased CRP and TNF-α; sweets and desserts (dark chocolate) decreased IL-6). The certainty of evidence was moderate-to-low for the majority of analyses. CONCLUSIONS: Food source appears to mediate the effect of fructose-containing sugars on inflammatory markers over the short-to-medium term. The evidence provides good indication that mixed sources that contain SSBs increase CRP, while most other food sources have no effect with some sources (fruit, 100% fruit juice, sweetened soy beverage or dark chocolate) showing decreases, which may be dependent on energy control. CLINICALTRIALS: gov: (NCT02716870).

Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

Decreasing the RAG:SAG ratio of granola cereal predictably reduces postprandial glucose and insulin responses: a report of four randomised trials in healthy adults.

Dietary starch contains rapidly (RAG) and slowly available glucose (SAG). To establish the relationships between the RAG:SAG ratio and postprandial glucose, insulin and hunger, we measured postprandial responses elicited by test meals varying in the RAG:SAG ratio in n 160 healthy adults, each of whom participated in one of four randomised cross-over studies (n 40 each): a pilot trial comparing six chews (RAG:SAG ratio 2·4-42·7) and three studies comparing a test granola (TG1-3, RAG:SAG ratio 4·5-5·2) with a control granola (CG1-3, RAG:SAG ratio 54·8-69·3). Within studies, test meals were matched for fat, protein and available carbohydrate. Blood glucose, serum insulin and subjective hunger were measured for 3 h. Data were subjected to repeated-measures analysis of variance (ANOVA). The relationships between the RAG:SAG ratio and postprandial end points were determined by regression analysis. In the pilot trial, 0-2 h glucose incremental areas under the curve (iAUC0-2; primary end point) varied across the six chews (P = 0·014) with each 50 % reduction in the RAG:SAG ratio reducing relative glucose response by 4·0 %. TGs1-3 elicited significantly lower glucose iAUC0-2 than CGs1-3 by 17, 18 and 17 %, respectively (similar to the 15 % reduction predicted by the pilot trial). The combined means ± sem (n 120) for TC and CG were glucose iAUC0-2, 98 ± 4 v. 118 ± 4 mmol × min/l (P < 0·001), and insulin iAUC0-2, 153 ± 9 v. 184 ± 11 nmol × h/l (P < 0·001), respectively. Neither postprandial hunger nor glucose or hunger increments 2 h after eating differed significantly between TG and CG. We concluded that TGs with RAG:SAG ratios <5·5 predictably reduced glycaemic and insulinaemic responses compared with CGs with RAG:SAG ratios >54. However, compared with CG, TG did not reduce postprandial hunger or delay the return of glucose or hunger to baseline.

Canned Beans Decrease Serum Total and LDL Cholesterol in Adults with Elevated LDL Cholesterol in a 4-wk Multicenter, Randomized, Crossover Study.

BACKGROUND: Practical risk reduction strategies are needed to address cardiovascular disease. Beans can decrease LDL cholesterol; however, research into different daily amounts and varieties is warranted. OBJECTIVES: To examine the effects of canned beans (daily rotation of black, navy, pinto, dark red kidney, white kidney) in 1-cup (1CB, 180 g) and ½-cup (½CB, 90 g) daily amounts compared with a 1-cup white rice (WR) control on serum lipid and glycemic biomarkers in adults with elevated LDL cholesterol. METHODS: Adults [n = 73, mean ± SD age: 48.1 ± 14.2 y; BMI (in kg/m2): 25.9 ± 4.22; fasting serum LDL cholesterol: 3.0-5.0 mmol/L] consumed 1CB, ½CB, and WR for 4-wk treatment periods separated by ≥4-wk washouts in a multicenter, randomized, crossover study. Fasting serum LDL cholesterol (primary outcome) and other lipids and glycemic biomarkers (secondary outcomes) were measured on study days 1 and 29 of each treatment period with study day 29 values compared using repeated-measures ANCOVA, including study day 1 values as covariates. RESULTS: Treatment completion was n = 66 for 1CB, n = 68 for ½CB, and n = 64 for WR. Total cholesterol on study day 29 was lower for 1CB (P = 0.04) but not ½CB (P = 0.77) compared with WR (-5.46%, -2.74%, -0.65% changes from study day 1, respectively) and did not differ between 1CB and ½CB (P = 0.17). LDL cholesterol on study day 29 was also lower for 1CB (P = 0.002) but not ½CB (P = 0.30) compared with WR (-8.08%, -3.84%, +0.49% changes from study day 1, respectively) and did not differ between 1CB and ½CB (P = 0.11). Other lipids and glycemic biomarkers did not differ among treatments. CONCLUSIONS: Consumption of 1 cup (180 g) of canned beans of multiple varieties decreased total and LDL cholesterol in adults with elevated LDL cholesterol, supporting a practical strategy for cardiovascular disease risk reduction. This trial was registered at clinicaltrials.gov as NCT03830970.

Dietary Glycaemic Index Labelling: A Global Perspective.

The glycaemic index (GI) is a food metric that ranks the acute impact of available (digestible) carbohydrates on blood glucose. At present, few countries regulate the inclusion of GI on food labels even though the information may assist consumers to manage blood glucose levels. Australia and New Zealand regulate GI claims as nutrition content claims and also recognize the GI Foundation's certified Low GI trademark as an endorsement. The GI Foundation of South Africa endorses foods with low, medium and high GI symbols. In Asia, Singapore's Healthier Choice Symbol has specific provisions for low GI claims. Low GI claims are also permitted on food labels in India. In China, there are no national regulations specific to GI; however, voluntary claims are permitted. In the USA, GI claims are not specifically regulated but are permitted, as they are deemed to fall under general food-labelling provisions. In Canada and the European Union, GI claims are not legal under current food law. Inconsistences in food regulation around the world undermine consumer and health professional confidence and call for harmonization. Global provisions for GI claims/endorsements in food standard codes would be in the best interests of people with diabetes and those at risk.

Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Library searched up to 13 May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. OUTCOME AND MEASURES: The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. RESULTS: 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. CONCLUSIONS: This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. STUDY REGISTRATION: ClinicalTrials.gov NCT04045938.

Neither low salivary amylase activity, cooling cooked white rice, nor single nucleotide polymorphisms in starch-digesting enzymes reduce glycemic index or starch digestibility: a randomized, crossover trial in healthy adults.

BACKGROUND: It was suggested that low salivary-amylase activity (SAA) and cooling or stir-frying cooked starch decreases its digestibility and glycemic index. OBJECTIVE: We determined the effects of SAA, cooling, and single-nucleotide polymorphisms (SNPs) in the salivary amylase (AMY1), pancreatic amylase (AMY2A, AMY2B), maltase-glucoamylase (MGAM), and sucrase-isomaltase (SI) genes on starch digestibility and glycemic index of cooked polished rice. METHODS: Healthy subjects [pilot, n = 12; main, n = 20 with low-SAA (<50 U/mL), and n = 20 with high-SAA (>105 U/mL)] consumed test meals containing 25 g (pilot) or 50 g (main) available carbohydrate at a contract research organization using open-label (pilot) or assessor-blinded (main), randomized, crossover, Latin-square designs (trial registration: NCT03667963). Pilot-trial test meals were dextrose, freshly cooked polished rice, cooked rice cooled overnight, stir-fried hot rice, or stir-fried cold rice. Main-trial test meals were dextrose, dextrose plus 10 g lactulose, plain hot rice, or plain cold rice. In both trials, blood glucose was measured fasting and at intervals over 2 h. In the main trial, breath hydrogen was measured fasting and hourly for 6 h to estimate in vivo starch digestibility. Data were analyzed by repeated-measures ANOVA for the main effects of temperature and stir-frying (pilot trial) or the main effects of SAA and temperature (main trial) and their interactions. Effects of 24 single nucleotide polymorphisms (SNPs) were assessed separately. Means were considered to be equivalent if the 95% CI of the differences were within ±20% of the comparator mean for glucose response/glycemic index or ±7% for digestibility. RESULTS: Pilot: neither temperature nor stir-frying significantly affected glucose incremental AUC (primary endpoint, n = 12). Main: mean ± SEM glycemic index (primary endpoint, n = 40) was equivalent for low-SAA compared with high-SAA (73 ± 3 vs. 75 ± 4) and cold rice compared with hot rice (75 ± 3 vs. 70 ± 3). Estimated starch digestibility (n = 39) was equivalent for low-SAA compared with high-SAA (95% ± 1% vs. 92% ± 1%) and hot rice compared with cold rice (94% ± 1% vs. 93% ± 1%). No meaningful associations were observed between genotypes and starch digestibility or glycemic index for any of the SNPs. CONCLUSIONS: The results do not support the hypotheses that low-SAA, cooling, and common genetic variations in starch-digesting enzymes affect the glycemic index or in vivo carbohydrate digestibility of cooked polished rice. This trial was registered at clinicaltrials.gov as NCT03667963.

Effect of Oat ß-Glucan on Affective and Physical Feeling States in Healthy Adults: Evidence for Reduced Headache, Fatigue, Anxiety and Limb/Joint Pains.

The gastrointestinal (GI) side-effects of dietary fibers are recognized, but less is known about their effects on non-GI symptoms. We assessed non-GI symptoms in a trial of the LDL-cholesterol lowering effect of oat ß-glucan (OBG). Participants (n = 207) with borderline high LDL-cholesterol were randomized to an OBG (1 g OBG, n = 104, n = 96 analyzed) or Control (n = 103, n = 95 analyzed) beverage 3-times daily for 4 weeks. At screening, baseline, 2 weeks and 4 weeks participants rated the severity of 16 non-GI symptoms as none, mild, moderate or severe. The occurrence and severity (more or less severe than pre-treatment) were compared using chi-squared and Fisher's exact test, respectively. During OBG treatment, the occurrence of exhaustion and fatigue decreased versus baseline (p < 0.05). The severity of headache (2 weeks, p = 0.032), anxiety (2 weeks p = 0.059) and feeling cold (4 weeks, p = 0.040) were less on OBG than Control. The severity of fatigue and hot flashes at 4 weeks, limb/joint pain at 2 weeks and difficulty concentrating at both times decreased on OBG versus baseline. High serum c-reactive-protein and changes in c-reactive-protein, oxidized-LDL, and GI-symptom severity were associated with the occurrence and severity of several non-GI symptoms. These data provide preliminary, hypothesis-generating evidence that OBG may reduce several non-GI symptoms in healthy adults.

The effect of oat ß-glucan on postprandial blood glucose and insulin responses: a systematic review and meta-analysis.

To determine the effect of oat ß­glucan (OBG) on acute glucose and insulin responses and identify significant effect modifiers we searched the MEDLINE, EMBASE, and Cochrane databases through October 27, 2020 for acute, crossover, controlled feeding trials investigating the effect of adding OBG (concentrate or oat-bran) to carbohydrate-containing test-meals compared to comparable or different carbohydrate-matched control-meals in humans regardless of health status. The primary outcome was glucose incremental area-under-the-curve (iAUC). Secondary outcomes were insulin iAUC, and glucose and insulin incremental peak-rise (iPeak). Two reviewers extracted the data and assessed risk-of-bias and certainty-of-evidence (GRADE). Data were pooled using generic inverse-variance with random-effects model and expressed as ratio-of-means with [95% CIs]. We included 103 trial comparisons (N = 538). OBG reduced glucose iAUC and iPeak by 23% (0.77 [0.74, 0.81]) and 28% (0.72 [0.64, 0.76]) and insulin by 22% (0.78 [0.72, 0.85]) and 24% (0.76 [0.65, 0.88]), respectively. Dose, molecular-weight, and comparator were significant effect modifiers of glucose iAUC and iPeak. Significant linear dose-response relationships were observed for all outcomes. OBG molecular-weight >300 kg/mol significantly reduced glucose iAUC and iPeak, whereas molecular-weight <300 kg/mol did not. Reductions in glucose iAUC (27 vs 20%, p = 0.03) and iPeak (39 vs 25%, p < 0.01) were significantly larger with different vs comparable control-meals. Outcomes were similar in participants with and without diabetes. All outcomes had high certainty-of-evidence. In conclusion, current evidence indicates that adding OBG to carbohydrate-containing meals reduces glycaemic and insulinaemic responses. However, the magnitude of glucose reduction depends on OBG dose, molecular-weight, and the comparator.

Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes.

AIM: Omega-3 (n-3) polyunsaturated fatty-acids are essential for the development and maintenance of nerve function, but the relationship of plasma n-3 to the presence of diabetic distal-symmetric-polyneuropathy (DSP) and the effect of n-3 therapy on plasma levels and small nerve fibre morphology in T1D are unknown. METHODS: Participants with T1D (n = 40, 53% female, aged (mean ±â€¯SD) 48 ±â€¯14 years, BMI 28.1 ±â€¯5.8 kg/m2, diabetes duration 27 ±â€¯18 years), 23 of whom had DSP, took seal-oil (10 mL/day; 750 mg eicosapentaenoic acid (EPA), 560 mg docosapentaenoic acid (DPAn-3), and 1020 mg docosahexaenoic acid (DHA)) for 12-months in a single-arm open-label study. The improvement in corneal nerve fibre length (CNFL) (primary outcome) was previously reported. In this secondary analysis, plasma n-3s were measured at baseline, 4, 8 and 12-months. RESULTS: At baseline, participants with DSP had lower DHA than those without (1.73 ±â€¯0.89 vs. 2.27 ±â€¯0.70%, p = 0.049). Twelve-months seal-oil therapy increased mean plasma EPA by 185%, DPA by 29%, DHA by 79% (p < 0.001) and CNFL by 29% (p = 0.001). Change in CNFL was positively associated with higher baseline total n-3 (Spearman's correlation coefficient r = 0.41, p = 0.013), DPA (r = 0.33, p = 0.047) and DHA (r = 0.42, p = 0.012). CONCLUSION: In conclusion, low plasma DHA was associated with prevalent DSP, n-3 therapy increased blood n-3 levels and higher baseline n-3s were associated with greater nerve regeneration.

Effect of Varying Molecular Weight of Oat ß-Glucan Taken just before Eating on Postprandial Glycemic Response in Healthy Humans.

To see if the molecular weight (MW) and viscosity of oat ß-glucan (OBG) when taken before eating determine its effect on postprandial glycemic responses (PPRG), healthy overnight-fasted subjects (n = 16) were studied on eight separate occasions. Subjects consumed 200 mL water alone (Control) or with 4 g OBG varying in MW and viscosity followed, 2-3 min later, by 113 g white-bread. Blood was taken fasting and at 15, 30, 45, 60, 90, and 120 min after starting to eat. None of the OBG treatments differed significantly from the Control for the a-priori primary endpoint of glucose peak-rise or secondary endpoint of incremental area-under-the-curve (iAUC) over 0-120 min. However, significant differences from the Control were seen for glucose iAUC over 0-45 min and time to peak (TTP) glucose. Lower log(MW) and log(viscosity) were associated with higher iAUC 0-45 (p < 0.001) and shorter TTP (p < 0.001). We conclude that when 4 g OBG is taken as a preload, reducing MW does not affect glucose peak rise or iAUC0-120, but rather accelerates the rise in blood glucose and reduces the time it takes glucose to reach the peak. However, this is based on post-hoc calculation of iAUC0-45 and TTP and needs to be confirmed in a subsequent study.

Dietary Fibre Consensus from the International Carbohydrate Quality Consortium (ICQC).

Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.

Effect of a Snack Bar Optimized to Reduce Alcohol Bioavailability: A Randomized Controlled Clinical Trial in Healthy Individuals.

Alcohol intoxication impairs judgment and reaction times and the level of blood alcohol concentration (BAC) is highly correlated with accidents and injury. We hypothesized that a food optimized to delay gastric emptying, a reduced alcohol bioavailability bar (RABB), would decrease postprandial BAC and alcohol bioavailability with greater caloric-efficiency than control foods. Therefore, we evaluated the RABB in a randomized, crossover trial in 21 overnight fasted healthy adults (10 male, 11 female). Just before consuming a moderate dose of alcohol (0.3-0.35 g/kg body weight), participants ate either (1) no food (NF, 0 kcal), (2) the RABB (210 kcal), (3) a savory snack mix (SSM, 210 kcal), or (4) a multicomponent meal (MCM, 635 kcal) and their BAC was measured over 90 minutes using a breathalyzer, the primary endpoint being peak BAC (pBAC). pBACs were analyzed by repeated measures analysis of variance (ANOVA) (F = 107.5, P < .0001) with the differences between means assessed using Tukey's honestly significant difference test. The pBAC of each group was different (P < .001) from all other groups (NF = 0.064 ± 0.003, SSM = 0.047 ± 0.002, RABB = 0.031 ± 0.002, MCM = 0.020 ± 0.002%; mean ± standard error of the mean). Furthermore, the bioavailability of alcohol over 90 minutes (BA90) was reduced compared to the NF group by similar margins (SSM = 22.0 ± 2.2, RABB = 45.0 ± 3.8, MCM = 67.9 ± 3.1%) with the mean BA90 of each group different from all other groups (P < .001). Compared to the NF condition, the average reduction of pBAC per 100 calories of food consumed was higher for the RABB (24.0%) than either the SSM (11.8%) or the MCM (10.7%). This study demonstrates that the RABB can reduce both pBAC and alcohol bioavailability with high caloric-efficiency.

Increasing oat ß-glucan viscosity in a breakfast meal slows gastric emptying and reduces glycemic and insulinemic responses but has no effect on appetite, food intake, or plasma ghrelin and PYY responses in healthy humans: a randomized, placebo-controlled, crossover trial.

BACKGROUND: The viscosity of oat ß-glucan (OBG) determines its effect on serum cholesterol and glycemic responses, but whether OBG viscosity affects gastric emptying, appetite, and ad libitum food intake is unknown. OBJECTIVES: We aimed to determine the effect of altering the amount or molecular weight (MW) and, hence, viscosity of OBG in a breakfast meal on the primary endpoint of food intake at a subsequent meal. METHODS: Overnight-fasted males (n = 16) and nonpregnant females (n = 12) without diabetes, aged 18-60 y, with BMI 20.0-30.0 kg/m² who were unrestrained eaters participated in a double-blind, randomized, crossover study at a contract research organization. Participants consumed, in random order, breakfast meals equivalent in weight, energy, and macronutrients consisting of white-bread, butter, jam, and 2% milk plus hot cereal [Cream of Rice (CR), or instant-oatmeal plus either 3 g oat-bran (2gOBG), 10 g oat-bran (4gOBG), or 10 g oat-bran plus ß-glucanase (4gloMW) to reduce OBG MW and viscosity compared with 4gOBG]. Gastric emptying, subjective appetite, and glucose, insulin, ghrelin, and peptide tyrosine tyrosine (PYY) responses were assessed for 3 h and then subjects were offered an ad libitum lunch (water and pizza). RESULTS: Pizza intakes (n = 28) after CR, 2gOBG, 4gOBG, and 4gloMW (mean ± SEM: 887 ± 64, 831 ± 61, 834 ± 78, and 847 ± 68 kcal, respectively) were similar (nonsignificant). Compared with CR, 4gOBG significantly reduced glucose (78 ± 10 compared with 135 ± 15 mmol × min/L) and insulin (14.0 ± 1.6 compared with 26.8 ± 3.5 nmol × min/L) incremental area-under-the-curve and delayed gastric-emptying half-time (geometric mean: 285; 95% CI: 184, 442, compared with geometric mean: 105; 95% CI: 95, 117 min), effects not seen after 4gloMW. Subjective appetite, PYY, and ghrelin responses after 2gOBG, 4gOBG, and 4gloMW were similar to those after CR. CONCLUSIONS: The results demonstrate that OBG viscosity determines its effect on postprandial glucose, insulin, and gastric emptying. However, we were unable to demonstrate a significant effect of OBG on appetite or food intake, regardless of its viscosity.This trial was registered at clinicaltrials.gov as NCT03490851.