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Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.
Yoshino, M, Yoshino, J, Kayser, BD, Patti, GJ, Franczyk, MP, Mills, KF, Sindelar, M, Pietka, T, Patterson, BW, Imai, SI, et al
Science (New York, N.Y.). 2021;372(6547):1224-1229
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Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for NAD+-consuming enzymes that are essential in the regulation of diverse biological processes. The aim of this study was to determine the effects of nicotinamide mononucleotide (NMN) supplementation on i) body composition, ii) skeletal muscle insulin sensitivity, and insulin signalling; and iii) muscle NAD+ content and global gene expression profile. This study is a 10-week, randomized, placebo-controlled, double-blind trial in postmenopausal women with prediabetes who were overweight or obese. Twenty-five postmenopausal women with prediabetes were randomised to the placebo group (n=12) or the NMN group (n=13). Results show that 10 weeks of NMN supplementation increases muscle insulin signalling and muscle insulin sensitivity in postmenopausal women with prediabetes who are overweight or obese. Authors conclude that the precise mechanism(s) responsible for these metabolic effects and the potential metabolic benefits of NMN supplementation in other patient populations remain to be explored.
Abstract
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese (clinicaltrial.gov NCT03151239).
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A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.
Bittel, AJ, Bittel, DC, Mittendorfer, B, Patterson, BW, Okunade, AL, Abumrad, NA, Reeds, DN, Cade, WT
Medicine and science in sports and exercise. 2021;53(4):694-703
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Prediabetes is a metabolic condition defined by elevated fasting (impaired fasting glucose) and/or postprandial (impaired glucose tolerance) plasma glucose. The aim of this study was to determine the effects of a single bout of resistance exercise on postprandial glucose metabolism following a mixed meal in obese, sedentary men with prediabetes. This study is a randomised, cross-over study design which enrolled ten participants. Participants were aged 39-62 years, obese, and demonstrated insulin resistance with compensatory increases in beta cell function. Results show that a single bout of resistance exercise performed 4.5 hours before a mixed meal (as opposed to an oral glucose tolerance test) reduced total postprandial glucose appearance, increased insulin sensitivity, and reduced the glycaemic response to a mixed meal. However, it did not have effect on glucose oxidation in obese men with prediabetes. Improvements in insulin sensitivity were complemented by reduced postprandial insulin concentration. Authors conclude that further investigation is needed to elucidate how resistance exercise affects exogenous (meal) vs endogenous postprandial glucose metabolism, and if additional bouts of exercise (i.e. training) produce superior outcomes for this population.
Abstract
INTRODUCTION Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes. METHODS We studied 10 sedentary men with obesity (body mass index, 33 ± 3 kg·m-2) and prediabetes by using a randomized, cross-over study design. After an overnight fast, participants completed either a single bout of whole-body RE (seven exercises, 3 sets of 10-12 repetitions at 80% one-repetition maximum each) or an equivalent period of rest. Participants subsequently completed a mixed meal test in conjunction with an intravenous [6,6-2H2]glucose infusion to determine basal and postprandial glucose rate of appearance (Ra) and disappearance (Rd) from plasma, insulin sensitivity, and the insulinogenic index (a measure of beta cell function). Skeletal muscle biopsies were obtained 90 min postmeal to evaluate pyruvate-supported and maximal mitochondrial respiration. Whole-body carbohydrate oxidation was assessed using indirect calorimetry. RESULTS RE significantly reduced the postprandial rise in glucose Ra and plasma glucose concentration. Postprandial insulin sensitivity was significantly greater after RE, whereas postprandial plasma insulin concentration was significantly reduced. RE had no effect on the insulinogenic index, postprandial pyruvate respiration, or carbohydrate oxidation. CONCLUSION/INTERPRETATION A single bout of RE has beneficial effects on postprandial glucose metabolism in men with obesity and prediabetes by increasing postprandial insulin sensitivity, reducing the postprandial rise in glucose Ra, and reducing postprandial plasma insulin concentration.
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The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE.
Lee, AK, Woodward, M, Wang, D, Ohkuma, T, Warren, B, Sharrett, AR, Williams, B, Marre, M, Hamet, P, Harrap, S, et al
The Journal of clinical endocrinology and metabolism. 2020;105(1)
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Type 2 diabetes is characterized by metabolic dysregulation resulting in an increased risk of cardiovascular disease The objectives of this study were: a. to determine whether weight change over 2 years was associated with subsequent cardiovascular outcomes and death in adults with diabetes, and b. to examine whether this association was modified by baseline body mass index (BMI), age, or type of glucose-lowering medications. This study is a large prospective study of adults with type 2 diabetes. One arm tested the effects of intensive glucose lowering versus standard glucose control. Whereas the second arm tested the effects of blood pressure-lowering medication versus a placebo. Results showed that that >10% weight loss was associated with >2 times higher risk of cardiovascular and all-cause mortality and was associated with 75% greater risk of major macrovascular events, compared with adults with stable weight. These associations were not significantly modified by metformin use, age, or baseline BMI. Authors conclude that unless patients specifically report lifestyle changes to lose weight, even modest weight loss may be a marker of declining health for which further clinical investigation is merited.
Abstract
CONTEXT Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN AND SETTING The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. CONCLUSIONS In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.
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Honey does not adversely impact blood lipids of adult men and women: a randomized cross-over trial.
Al-Tamimi, AM, Petrisko, M, Hong, MY, Rezende, L, Clayton, ZS, Kern, M
Nutrition research (New York, N.Y.). 2020;74:87-95
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Restriction of sugar intake is among the most commonly advocated public health strategies, as it is believed to prevent the development of chronic diseases. Unlike sugar, honey has been shown to have various positive health benefits from increasing antioxidant status to lowering postprandial [after a meal] glycaemia and insulinaemia in healthy subjects when compared to responses of more highly refined sugar mixtures. The aim of this study was to assess responses to both short-term (1 week) and relatively long-term (1 month) ingestion of clover honey consumption versus sucrose on changes in dietary intake and serum lipid concentrations in young to middle-aged adults. This study is a crossover design randomised controlled study for which 40 participants were recruited (male [n = 21] and female [n = 19]) with an age range between 25 and 57 years. Results indicate that consumption of clover honey (1.2 g of carbohydrate per kilogram body weight) for up to 1 month produced modestly positive dietary and triglyceride effects compared to sucrose. - there were no positive lipid effects within the clover honey trial. - compared to sucrose, clover honey consumption resulted in a significantly lower intake of energy, carbohydrate, sugars and fat as well as lower triglycerides concentrations at the end of 4 weeks. Authors conclude that honey produces limited, modest health benefits relative to sucrose. Future studies are needed to investigate the possible mechanisms by which honey influences triglyceride production and/or clearance and the metabolic and hormonal regulators of food intake.
Abstract
Consumption of added sugars in the US is estimated to be approximately 1.5 times recommended levels and has been linked to increased risk for developing chronic diseases. We hypothesized that relative to sugar, honey would reduce energy intake and improve serum lipid profiles. To test this, we assessed the short-term (1-week) and relatively long-term (1-month) effects of honey versus sucrose on changes in dietary intake and serum lipid concentrations. Thirty-seven apparently healthy subjects (21 males; 16 females) aged 24-57 years (BMI = 17.6-37.2 kg/m2) completed two 4-week trials in a randomized, cross-over design separated by ≥4-week washout. During each trial, subjects consumed either clover honey or sucrose providing 1.2 g/kg/day of carbohydrate under free-living conditions with instructions to avoid changing their habitual food intake. Serum triglyceride (TG) concentrations were elevated (P < .05) after 1 week for both trials but only remained elevated (P < .05) at the 4-week time-point during sucrose consumption. The elevation after 1 week during the honey trial was concurrent with a transient increase (P < .05) in body weight. No effects on serum concentrations of insulin, total cholesterol, low density lipoprotein-cholesterol, or high density lipoprotein-cholesterol were detected for either trial. Subjects consumed significantly less energy (P < .05), carbohydrate (P < .005), sugars (P < .05), and saturated fat (P < .05) during the honey trial. These data suggest that honey may serve as a favorable substitute for sucrose with regard to reduced energy intake, carbohydrate and sugars, without negatively influencing serum lipid concentrations.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study.
Runchey, SS, Pollak, MN, Valsta, LM, Coronado, GD, Schwarz, Y, Breymeyer, KL, Wang, C, Wang, CY, Lampe, JW, Neuhouser, ML
European journal of clinical nutrition. 2012;66(10):1146-52
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Dietary intervention studies have shown detrimental metabolic effects of high-glycaemic load diets. The glycaemic index (GI) is the numerical classification of a particular food’s blood glucose-raising effect. The aim of this study was to evaluate the effect of a high-glycaemic load diet on circulating levels of insulin-like growth factor-1 (IGF-1) [hormone] and insulin-like growth factor-binding protein 3 (IGFBP-3) [protein] compared to a low-glycaemic load diet. The study is a randomised controlled crossover study which enrolled 84 normal weight and overweight-obese healthy individuals. The study included two 28-day weight-maintaining high- and low-glycaemic load diets. Results indicate that consumption of a low-glycaemic load diet resulted in lower post-prandial [after a meal] insulin and glucose responses and modestly lower fasting IGF-1 and IGF-1/IGFBP-3 concentrations. However, there were no observable effects of glycaemic load on insulin resistance or glucose-adjusted post-prandial insulin responses in these healthy participants. Authors conclude that further intervention studies are required in order to weigh the impact of dietary glycaemic load on risk for chronic disease.
Abstract
BACKGROUND/OBJECTIVES The effect of a low glycemic load (GL) diet on insulin-like growth factor-1 (IGF-1) concentration is still unknown but may contribute to lower chronic disease risk. We aimed to assess the impact of GL on concentrations of IGF-1 and IGF-binding protein-3 (IGFBP-3). SUBJECTS/METHODS We conducted a randomized, controlled crossover feeding trial in 84 overweight obese and normal weight healthy individuals using two 28-day weight-maintaining high- and low-GL diets. Measures were fasting and post-prandial concentrations of insulin, glucose, IGF-1 and IGFBP-3. In all 80 participants completed the study and 20 participants completed post-prandial testing by consuming a test breakfast at the end of each feeding period. We used paired t-tests for diet component and linear mixed models for biomarker analyses. RESULTS The 28-day low-GL diet led to 4% lower fasting concentrations of IGF-1 (10.6 ng/ml, P=0.04) and a 4% lower ratio of IGF-1/IGFBP-3 (0.24, P=0.01) compared with the high-GL diet. The low-GL test breakfast led to 43% and 27% lower mean post-prandial glucose and insulin responses, respectively; mean incremental areas under the curve for glucose and insulin, respectively, were 64.3±21.8 (mmol/l/240 min; P<0.01) and 2253±539 (μU/ml/240 min; P<0.01) lower following the low- compared with the high-GL test meal. There was no effect of GL on mean homeostasis model assessment for insulin resistance or on mean integrated post-prandial concentrations of glucose-adjusted insulin, IGF-1 or IGFBP-3. We did not observe modification of the dietary effect by adiposity. CONCLUSIONS Low-GL diets resulted in 43% and 27% lower post-prandial responses of glucose and insulin, respectively, and modestly lower fasting IGF-1 concentrations. Further intervention studies are needed to weigh the impact of dietary GL on risk for chronic disease.
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Plasma ghrelin concentrations are lower in binge-eating disorder.
Geliebter, A, Gluck, ME, Hashim, SA
The Journal of nutrition. 2005;135(5):1326-30
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Binge Eating Disorder (BED) is characterised by eating a large quantity of food (objectively) at least 2 times a week for 6 months, and is associated with a loss of feelings of self control. It is found it around 30% of obese individual who participate in weight loss programs. There may be a biological element to this disorder with possible mechanisms including heritability, an enlarged stomach capacity and genetic mutations. Hormones may also play a role in BED. This study aimed to establish whether obese individuals had higher fasting and post feeding ghrelin levels, and slower gastric emptying compared to a non-obese BED control group. 38 overweight and obese women were recruited and classified into one of three groups; non binge eaters (12), binge eaters but not meeting full BED criteria (14) and BED syndrome (11). 10 of the 11 BED women were randomly allocated to a 6 week treatment of either a) cognitive behavioural therapy (CBT) and a diet or b) a non treatment wait-list control. The study found that the BED women had a lower fasting ghrelin level and that ghrelin also declined less after a meal for this group. The authors stated that this appeared to be counterintuitive because ghrelin (which stimulates hunger) was expected to be higher for overweight and obese people. They suggest that binge eating may down-regulate ghrelin and be a response to over-eating (often when not hungry). They also suggested that ghrelin declining less for overweight and obese BED women may suggest that the magnitude of the ghrelin fall may be linked to higher satiation (so they have lower satiation and continue eating compared to other individuals).
Abstract
Binge-eating disorder (BED), characterized by binge meals without purging afterward, is found in about 30% of obese individuals seeking treatment. The study objective was to ascertain abnormalities in hormones influencing appetite in BED, especially ghrelin, an appetite-stimulating peptide, which was expected to be elevated. Measurements were made of plasma insulin, leptin, glucagon, cholecystokinin, and ghrelin, as well as glucose following an overnight 12-h fast, prior to and after ingestion (from 0 to 5 min) of a nutritionally complete liquid meal (1254 kJ) at 0830 h, at -15, 0, 5, 15, 30, 60, 90, and 120 min. Appetite ratings including hunger and fullness were also obtained. An acetaminophen tracer was used to assess gastric emptying rate. Three groups of comparably obese women (BMI = 35.9 +/- 5.5; % body fat = 44.9 +/- 4.7) participated: 12 nonbinge eating normals (NB), 14 subthreshold BED, and 11 BED. The BED subjects, compared to NB subjects, had lower baseline ghrelin concentrations prior to the meal, a lower area under the curve (AUC), with lower levels at 5, 15, 30, 90, and 120 min, and a smaller decline in ghrelin postmeal (all P < 0.03). The other blood values did not differ among groups, and neither did gastric emptying rate nor ratings of fullness. The BED subjects were then randomly assigned to treatment with cognitive-behavior therapy and diet (n = 5) or to a wait-list control (n = 4). Baseline ghrelin (P = 0.01) and AUC increased (P = 0.02), across both conditions, in which most subjects (7 of 9) stopped binge eating. The lower fasting and postmeal plasma ghrelin levels in BED are consistent with lower ghrelin levels in obese compared to lean individuals and suggests downregulation by binge eating.