Biomimetic cellulose-based superabsorbent hydrogels for treating obesity.

In the treatment of obesity, nutritional and behavioral modifications are difficult to implement and maintain. Since vegetable consumption is a fundamental part of many dietary interventions and daily nutrient requirements, we developed a novel cellulose-based superabsorbent hydrogel (CB-SAH) platform, inspired by the composition and mechanical properties of raw vegetables, as a mechanobiological therapy. The CB-SAHs properties were studied in a simulated gastrointestinal environment, while their impact on gut tissue was investigated by an ex vivo organ culture (EVOC) model. Functional fibers and raw vegetables were used as reference. CB-SAHs demonstrated orders of magnitude higher elasticity in comparison to the tested functional fibers, however performed similar to the tested raw vegetables. Notably, the biomimetic CB-SAHs with elasticity levels similar to raw vegetables showed benefits in preserving and regulating the gut tissue in the EVOC model. Non-systemic oral mechanotherapeutics based on this technology were advanced through clinical studies, with a first product cleared as an aid for weight management in the US and Europe.

Pretreatment Fasting Glucose and Insulin as Determinants of Weight Loss on Diets Varying in Macronutrients and Dietary Fibers-The POUNDS LOST Study.

Efforts to identify a preferable diet for weight management based on macronutrient composition have largely failed, but recent evidence suggests that satiety effects of carbohydrates may depend on the individual's insulin-mediated cellular glucose uptake. Therefore, using data from the POUNDS LOST trial, pre-treatment fasting plasma glucose (FPG), fasting insulin (FI), and homeostatic model assessment of insulin resistance (HOMA-IR) were studied as prognostic markers of long-term weight loss in four diets differing in carbohydrate, fat, and protein content, while assessing the role of dietary fiber intake. Subjects with FPG <100 mg/dL lost 2.6 (95% CI 0.9;4.4, p = 0.003) kg more on the low-fat/high-protein (n = 132) compared to the low-fat/average-protein diet (n = 136). Subjects with HOMA-IR ≥4 lost 3.6 (95% CI 0.2;7.1, p = 0.038) kg more body weight on the high-fat/high-protein (n = 35) compared to high-fat/average-protein diet (n = 33). Regardless of the randomized diet, subjects with prediabetes and FI below the median lost 5.6 kg (95% CI 0.6;10.6, p = 0.030) more when consuming ≥35 g (n = 15) compared to <35 g dietary fiber/10 MJ (n = 16). Overall, subjects with normal glycemia lost most on the low-fat/high-protein diet, subjects with high HOMA-IR lost most on the high-fat/high protein diet, and subjects with prediabetes and low FI had particular benefit from dietary fiber in the diet.

A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Personalized nutrition: pretreatment glucose metabolism determines individual long-term weight loss responsiveness in individuals with obesity on low-carbohydrate versus low-fat diet.

BACKGROUND/OBJECTIVES: The interaction between fasting plasma glucose (FPG) and fasting insulin (FI) concentrations and diets with different carbohydrate content were studied as prognostic markers of weight loss as recent studies up to 6 months of duration have suggested the importance of these biomarkers. SUBJECTS/METHODS: This was a retrospective analysis of a clinical trial where participants with obesity were randomized to an ad libitum low-carbohydrate diet or a low-fat diet with low energy content (1200-1800 kcal/day [≈ 5.0-7.5 MJ/d]; ≤ 30% calories from fat) for 24 months. Participants were categorized (pretreatment) as normoglycemic (FPG < 5.6 mmol/L) or prediabetic (FPG ≥ 5.6-6.9 mmol/L) and further stratified by median FI. Linear mixed models were used to examine outcomes by FPG and FI values. RESULTS: After 2 years, participants with prediabetes and high FI lost 7.2 kg (95% CI 2.1;12.2, P = 0.005) more with the low-fat than low-carbohydrate diet, whereas those with prediabetes and low FI tended to lose 6.2 kg (95% CI -0.9;13.3, P = 0.088) more on the low-carbohydrate diet than low-fat diet [mean difference: 13.3 kg (95% CI 4.6;22.0, P = 0.003)]. No differences between diets were found among participants with normoglycemia and either high or low FI (both P ≥ 0.16). CONCLUSIONS: Fasting plasma glucose and insulin are strong predictors of the weight loss response to diets with different macronutrient composition and might be a useful approach for personalized weight management.

Effect of a nonsystemic, orally administered hydrogel, GS100, on metformin pharmacokinetics.

Overweight and obesity are major health concerns worldwide, and are major predisposing factors for type 2 diabetes. This single-centre, Phase I, randomised, open-label, single-dose, 4-arm crossover, device-drug interaction study on 24 healthy volunteers with a body mass index of 25-40 kg/m2 tested the effect of a novel, nonsystemic, orally administered hydrogel (GS100) on the pharmacokinetics of an oral antidiabetic drug, metformin. When administered in both the fed and fasted states, the effect of GS100 on metformin pharmacokinetic characteristics was found to be similar to that of food. The type, frequency, and intensity of adverse events observed when GS100 was co-administered with metformin were similar to those observed with metformin alone. This study demonstrates that GS100 can be taken by patients receiving metformin, without altering the administration of metformin.

Personalized Dietary Management of Overweight and Obesity Based on Measures of Insulin and Glucose.

During the past several decades, numerous trials have compared various diets for the management of overweight and obesity, assuming that a single dietary strategy would be appropriate for all individuals. These studies have failed to provide strong evidence for the efficacy of any particular diet, and it is likely that different people will have different levels of success on different diets. We identified studies investigating pretreatment glycemia or insulinemia status, or both, of the individual as prognostic markers of weight loss during periods in which the composition of a participant's diet was known. Overall, research suggests that providing specific diets for weight management based on pretreatment glycemia and insulinemia statuses holds great promise for advancing personalized nutrition.

Pretreatment fasting plasma glucose and insulin modify dietary weight loss success: results from 3 randomized clinical trials.

Background: Which diet is optimal for weight loss and maintenance remains controversial and implies that no diet fits all patients.Objective: We studied concentrations of fasting plasma glucose (FPG) and fasting insulin (FI) as prognostic markers for successful weight loss and maintenance through diets with different glycemic loads or different fiber and whole-grain content, assessed in 3 randomized trials of overweight participants.Design: After an 8-wk weight loss, participants in the DiOGenes (Diet, Obesity, and Genes) trial consumed ad libitum for 26 wk a diet with either a high or a low glycemic load. Participants in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) Supermarket intervention (SHOPUS) trial consumed ad libitum for 26 wk the New Nordic Diet, which is high in fiber and whole grains, or a control diet. Participants in the NUGENOB (Nutrient-Gene Interactions in Human Obesity) trial consumed a hypocaloric low-fat and high-carbohydrate or a high-fat and low-carbohydrate diet for 10 wk. On the basis of FPG before treatment, participants were categorized as normoglycemic (FPG <5.6 mmol/L), prediabetic (FPG 5.6-6.9 mmol/L), or diabetic (FPG ≥7.0 mmol/L). Modifications of the dietary effects of FPG and FI before treatment were examined with linear mixed models.Results: In the DiOGenes trial, prediabetic individuals regained a mean of 5.83 kg (95% CI: 3.34, 8.32 kg; P < 0.001) more on the high- than on the low-glycemic load diet, whereas normoglycemic individuals regained a mean of 1.44 kg (95% CI: 0.48, 2.41 kg; P = 0.003) more [mean group difference: 4.39 kg (95% CI: 1.76, 7.02 kg); P = 0.001]. In SHOPUS, prediabetic individuals lost a mean of 6.04 kg (95% CI: 4.05, 8.02 kg; P < 0.001) more on the New Nordic Diet than on the control diet, whereas normoglycemic individuals lost a mean of 2.20 kg (95% CI: 1.21, 3.18 kg; P < 0.001) more [mean group difference: 3.84 kg (95% CI: 1.62, 6.06 kg); P = 0.001]. In NUGENOB, diabetic individuals lost a mean of 2.04 kg (95% CI: -0.20, 4.28 kg; P = 0.07) more on the high-fat and low-carbohydrate diet than on the low-fat and high-carbohydrate diet, whereas normoglycemic individuals lost a mean of 0.43 kg (95% CI: 0.03, 0.83 kg; P = 0.03) more on the low-fat and high-carbohydrate diet [mean group difference: 2.47 kg (95% CI: 0.20, 4.75 kg); P = 0.03]. The addition of FI strengthened these associations.Conclusion: Elevated FPG before treatment indicates success with dietary weight loss and maintenance among overweight patients consuming diets with a low glycemic load or with large amounts of fiber and whole grains. These trials were registered at clinicaltrials.gov as NCT00390637 (DiOGenes) and NCT01195610 (SHOPUS), and at ISRNCT.com as ISRCTN25867281 (NUGENOB).