Association between Plasma Trimethylamine N-Oxide Levels and Type 2 Diabetes: A Case Control Study

Animal and human studies have reported conflicting results on the relationship between circulating trimethylamine N-oxide (TMAO) levels and risk of Type 2 diabetes (T2D). This study aimed to compare plasma TMAO levels in people with or without T2D and explore the association of TMAO and T2D. A prospective case-control study of 297 participants, 164 healthy controls and 133 patients with T2D, was conducted. TMAO levels were quantified by UPLC-MS/MS. Comorbidities, dietary patterns, physical activity, and blood biomarkers were assessed. Median (IQR) plasma TMAO levels were significantly higher in diabetes cases (4.95 (2.84–8.35) µmol/L) compared to healthy controls (3.07 (2.05–4.82) µmol/L) (p < 0.001). The association between TMAO and T2D was significant in the non-adjusted Model 1 (p < 0.001) and after adjusting for confounders of diabetes including age, BMI, and level of education in Model 2 (p = 0.04). When the association was further adjusted for physical activity and diet in Model 3, plasma TMAO levels at only the highest quartile (>6.40 µmol/L) were associated with the risk of diabetes (OR = 3.36, 95% CI [1.26, 9.04], p = 0.02). The results presented suggest an association between plasma TMAO levels and T2D. A significant correlation was found between red meat consumption and increased levels of TMAO in T2D patients. A longitudinal study is warranted to further evaluate the correlation between TMAO and T2D.     

Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.     

Bifidobacterium breve and Bifidobacterium longum Attenuate Choline-Induced Plasma Trimethylamine N-Oxide Production by Modulating Gut Microbiota in Mice

Atherosclerosis is the main cause of myocardial infarction and stroke, and the morbidity and mortality rates of cardiovascular disease are among the highest of any disease worldwide. Excessive plasma trimethylamine-N-oxide (TMAO), an intestinal metabolite, promotes the development of atherosclerosis. Therefore, effective measures for reducing plasma TMAO production can contribute to preventing atherosclerosis. Probiotics are living microorganisms that are beneficial to the human body, and some of them can attenuate plasma TMAO production. To explore the effects of probiotic supplementation on plasma TMAO in choline-fed mice, we intragastrically administered eight strains of Bifidobacterium breve and eight strains of Bifidobacterium longum to mice for 6 weeks. B. breve Bb4 and B. longum BL1 and BL7 significantly reduced plasma TMAO and plasma and cecal trimethylamine concentrations. However, hepatic flavin monooxygenase (FMO) activity, flavin-containing monooxygenase 3 (FMO3), farnesoid X receptor (FXR) protein expression and TMAO fractional excretion were not significantly affected by Bifidobacterium supplementation. The treatment of Bifidobacterium strains modulated the abundances of several genera such as Ruminococcaceae UCG-009, Ruminococcaceae UCG-010, which belong to the Firmicutes that has been reported with cut gene clusters, which may be related to the reduction in intestinal TMA and plasma TMAO. Additionally, a reduction in Ruminococcaceae indicates a reduction in circulating glucose and lipids, which may be another pathway by which Bifidobacterium strains reduce the risk of atherosclerosis. The effect of Bifidobacterium strains on Bacteroides also suggests a relationship between the abundance of this genus and TMA concentrations in the gut. Therefore, the mechanism underlying these changes might be gut microbiota regulation. These Bifidobacterium strains may have therapeutic potential for alleviating TMAO-related diseases.     

Association of the Modified Mediterranean Diet Score (mMDS) with Anthropometric and Biochemical Indices in US Career Firefighters

The Mediterranean diet is associated with multiple health benefits, and the modified Mediterranean Diet Score (mMDS) has been previously validated as a measure of Mediterranean diet adherence. The aim of this study was to examine associations between the mMDS and anthropometric indices, blood pressure, and biochemical parameters in a sample of career firefighters. The participants were from Indiana Fire Departments, taking part in the “Feeding America’s Bravest” study, a cluster-randomized controlled trial that aimed to assess the efficacy of a Mediterranean diet intervention. We measured Mediterranean diet adherence using the mMDS. Anthropometric, blood pressure, and biochemical measurements were also collected. Univariate and multivariate linear regression models were used. In unadjusted analyses, many expected favorable associations between the mMDS and cardiovascular disease risk factors were found among the 460 firefighters. After adjustment for age, gender, ethnicity, physical activity, and smoking, a unitary increase in the mMDS remained associated with a decrease of the total cholesterol/HDL ratio (β-coefficient −0.028, p = 0.002) and an increase of HDL-cholesterol (β-coefficient 0.254, p = 0.004). In conclusion, greater adherence to the Mediterranean diet was associated with markers of decreased cardiometabolic risk. The mMDS score is a valid instrument for measuring adherence to the Mediterranean diet and may have additional utility in research and clinical practice.     

Sexual Dimorphism in Body Weight Loss,Improvements in Cardiometabolic Risk Factors and Maintenance of Beneficial Effects 6 Months after a Low-Calorie Diet: Results from the Randomized Controlled DiOGenes Trial

A low-calorie diet (LCD) is an effective strategy to lose weight and improve cardiometabolic risk factors, however, sexual dimorphism may be present. This study aims to investigate sexual dimorphism in cardiometabolic risk factors following weight loss and after weight maintenance. 782 overweight/obese participants (65% women) of the DiOGenes trial followed an 8-week LCD (~800 kcal/day), with a 6-months follow-up weight maintenance period on ad libitum diets varying in protein content and glycemic index. Men lost more body weight during the LCD period (−12.8 ± 3.9 vs. −10.1 ± 2.8 kg, respectively, p < 0.001), but regained more weight during the follow-up period than women (1.5 ± 5.4 vs. −0.5 ± 5.5 kg, respectively, p < 0.001). Even though beneficial LCD-induced changes in cardiometabolic risk factors were found for both sexes, improvements in HOMA-IR, muscle and hepatic insulin sensitivity, triacylglycerol, HDL−, LDL− and total cholesterol, diastolic blood pressure, cholesterol esters, sphingomyelins and adiponectin were more pronounced in men than women (std. ß range: 0.073–0.144, all q < 0.05), after adjustment for weight change. During follow-up, women demonstrated a lower rebound in HDL-cholesterol, triacylglycerol and diacylglycerol (std. ß range: 0.114–0.164, all q < 0.05), independent of changes in body weight. Overall, we demonstrated sexual dimorphism in LCD-induced changes in body weight and cardiometabolic risk profile, which may be attributed to differences in body fat distribution and metabolic status.     

Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (−0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.     

Weight Loss Is More Important Than the Diet Type in Improving Adiponectin Levels Among Overweight/Obese Adults

Objective: The study objective was to compare the effect of a standard calorie- and fat-restricted diet (STD-D) and a calorie- and fat-restricted lacto-ovo-vegetarian diet (LOV-D) on total and high-molecular-weight (HMW) adiponectin levels after 6 months of behavioral intervention.

Design: This study is an ancillary study to a randomized clinical trial.

Subjects: Subjects included 143 overweight/obese adults (STD-D = 79; LOV-D = 64).

Intervention: Both groups received the same standard behavioral intervention; the only difference was that LOV-D participants were instructed to eliminate meat, poultry, and fish from their diet.

Measures: Weight, dietary intake with the 3-day food diary, and total and HMW adiponectin levels were measured.

Results: Both groups significantly increased total (STD-D +7.2 ± 17.8%; LOV-D +9.4 ± 21.8%) and HMW adiponectin levels (STD-D +18.5 ± 32.9%; LOV-D +15.8 ± 34.5%; ps < 0.05) with no significant differences between the groups. We found significant associations between weight loss and increases in total (β (SE) = ?.071(.27); p = 0.003) and HMW adiponectin (β (SE) = ?1.37(.47); p = 0.001) levels independent of the diet type. Weight loss at the higher quartile was associated with improvements of adiponectin levels (p < 0.05).

Conclusion: Weight loss was associated with increased total and HMW adiponectin levels regardless of the diet type. Enhancing weight loss may be a means to improve adiponectin levels.     

Changes in Quantity and Sources of Dietary Fiber from Adopting Healthy Low-Fat vs. Healthy Low-Carb Weight Loss Diets: Secondary Analysis of DIETFITS Weight Loss Diet Study

The daily intake of dietary fiber is well below the recommended levels in the US. The effect of adopting a low-fat vs. a low-carbohydrate weight loss diet on fiber intake is of interest but not well-documented, especially when both approaches promote high-quality food choices. The objective of this paper is to compare the quantity and sources of dietary fiber between a healthy low-fat (HLF) vs. healthy low-carbohydrate (HLC) diet group when consumed over 12 months in a weight loss diet study. In this secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study, the amount and sources of dietary fiber were examined in generally healthy adults, 18–50 years of age, Body Mass Index (BMI) 28–40 kg/m², randomized to HLF or HLC for 12 months, who had available 24-h recalls at 0 (n = 609), 3 (n = 549), 6 (n = 491), and 12 (n = 449) months. The dietary intake was estimated by the Nutrition Data System for Research (NDS-R). The sources of fiber were determined for the major food groups. Significantly more total dietary fiber was consumed by HLF at every post-randomization time point, and, at 12 m, was 23.04 ± 9.43 g vs. 18.61 ± 8.12 g for HLF vs. HLC, respectively, p < 0.0001. In both diet groups at 12 months, the highest amount of dietary fiber came from non-starchy vegetables (4.13 ± 3.05 g and 5.13 ± 3.59 g). The other primary sources of fiber at 12 months for the HLF group were from whole grains (3.90 ± 3.13 g) and fruits (3.40 ± 2.87 g), and, for the HLC group, were from plant protein and fat sources, such as nuts and seeds, their butters, and avocados (2.64 ± 2.64 g). In the DIETFITS study, the difference in the total fiber intake for the HLF vs. HLC groups was more modest than expected. The HLC group consumed reasonably high amounts of fiber from high-protein and high fat plant-based sources.     

A High-Protein and Low-Glycemic Formula Diet Improves Blood Pressure and Other Hemodynamic Parameters in High-Risk Individuals

Low-caloric formula diets can improve hemodynamic parameters of patients with type 2 diabetes. We, therefore, hypothesized that persons with overweight or obesity can benefit from a high-protein, low-glycemic but moderate-caloric formula diet. This post-hoc analysis of the Almased Concept against Overweight and Obesity and Related Health Risk- (ACOORH) trial investigated the impact of a lifestyle intervention combined with a formula diet (INT, n = 308) compared to a control group with lifestyle intervention alone (CON, n = 155) on hemodynamic parameters (systolic and diastolic blood pressure (SBP, DBP), resting heart rate (HR), and pulse wave velocity (PWV)) in high-risk individuals with prehypertension or hypertension. INT replaced meals during the first 6 months (1 week: 3 meals/day; 2–4 weeks: 2 meals/day; 5–26 weeks: 1 meal/day). Study duration was 12 months. From the starting cohort, 304 (68.3%, INT: n = 216; CON: n = 101) participants had a complete dataset. Compared to CON, INT significantly reduced more SBP (−7.3 mmHg 95% CI [−9.2; −5.3] vs. −3.3 mmHg [−5.9; −0.8], p < 0.049) and DBP (−3.7 mmHg [−4.9; −2.5] vs. −1.4 mmHg [−3.1; 0.2], p < 0.028) after 12 months. Compared to CON, INT showed a pronounced reduction in resting HR and PWV after 6 months but both lost significance after 12 months. Changes in SBP, DBP, and PWV were significantly associated positively with changes in body weight and fat mass (all p < 0.05) and resting HR correlated positively with fasting insulin (p < 0.001) after 12 months. Combining a lifestyle intervention with a high-protein and low-glycemic formula diet improves hemodynamic parameters to a greater extent than lifestyle intervention alone in high-risk individuals with overweight and obesity.     

Healthy Eating Index Diet Quality in Randomized Weight Loss Trials: A Systematic Review

BackgroundWeight loss interventions focus on dietary and physical activity changes to induce weight loss. Both through weight loss and independent of it, diet quality is important for reducing chronic disease risk. However, whether and how diet quality changes over the course of a behavioral intervention is unclear.ObjectiveTo systematically review the evidence from randomized controlled trials on the effect of behavioral interventions on diet quality as defined by the Healthy Eating Index (HEI) among adults with overweight and obesity.MethodsPubMed, Ebscohost CINAHL, Embase, OVID APA PsycInfo, Scopus, and Web of Science were searched through May 2021. Inclusion criteria comprised randomized controlled trial design, a primary or secondary aim of weight loss, a sample of US adults with overweight or obesity, measurement using the HEI-2005, 2010, or 2015, and assessment of the time by treatment effect. Interventions must have included behavioral components and lasted at least 3 months. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. The systematic review protocol was published on Open Science Framework.ResultsOf 3,707 citations retrieved, 18 studies met inclusion criteria. A wide array of behavioral interventions were assessed, including in-person and mobile health interventions as well as those prescribing intake of specific foods. Risk of bias in the included studies primarily arose from the measurement of the outcome variable. Sample sizes ranged from 34 to 413 participants. Nine studies used multiple dietary recalls, with few using the recommended method of Healthy Eating Index calculation. Changes in diet quality ranged from no improvement to a 20-point improvement. More often, improvement was in the 4- to 7-point range.ConclusionsThe evidence for the efficacy of behavioral weight loss interventions for improving diet quality among adults with overweight and obesity is limited. Modest improvements in HEI scores were observed in the reviewed studies.     

Changes in Circulating Metabolites during Weight Loss and Weight Loss Maintenance in Relation to Cardiometabolic Risk

(1) Background: There is a substantial lack of knowledge of the biochemical mechanisms by which weight loss and weight regain exert their beneficial and adverse effects, respectively, on cardiometabolic outcomes. We examined associations between changes in circulating metabolites and changes in cardiometabolic risk factors during diet-induced weight loss and weight loss maintenance. (2) Methods: This prospective analysis of data from the Satiety Innovation (SATIN) study involved adults living with overweight and obesity (mean age=47.5). One hundred sixty-two subjects achieving ≥8% weight loss during an initial 8-week low-calorie diet (LCD) were included in a 12-week weight loss maintenance period. Circulating metabolites (m=123) were profiled using a targeted multiplatform approach. Data were analyzed using multivariate linear regression models. (3) Results: Decreases in the concentrations of several phosphatidylcholines (PCs), sphingomyelins (SMs), and valine were consistently associated with decreases in total (TChol) and low-density lipoprotein cholesterol (LDL-C) levels during the LCD. Increases in PCs and SMs were significantly associated with increases in TChol and LDL-C during the weight loss maintenance period. Decreases and increases in PCs during LCD and maintenance period, respectively, were associated with decreases in the levels of triglycerides. (4) Conclusions: The results of this study suggest that decreases in circulating PCs and SMs during weight loss and the subsequent weight loss maintenance period may decrease the cardiovascular risk through impacting TChol and LDL-C.     

Serum time curve characteristics of a fixed dose of beta-carotene in young and old men.

The present study was designed to evaluate age-related differences in serum beta-carotene time curve response characteristics when a beta-carotene dose was given in conjunction with 1500 kcal over the course of a day. On two consecutive days, seven old (73 +/? 4 years) and six young (24 +/? 1 years) men were each fed three 500-kcal meals of an isotonic liquid formula diet containing only trace amounts of beta-carotene. On the first day of testing, no supplemental beta-carotene was given (baseline day). A 15 mg dose of beta-carotene was fed with the morning meal on the second day (test dose day). Fasting blood and hourly blood samples were obtained for 8 consecutive hours on both days. Additional blood was drawn 24 and 48 hours after the test beta-carotene dose. There were no statistical differences in baseline beta-carotene concentrations between the two age groups tested, but, because of high individual variability, serum time curve characteristics were adjusted for fasting beta-carotene levels. After adjustment, the postdose serum beta-carotene response was two to three times greater (p less than or equal to 0.04) in young subjects, as evaluated by peak concentration, area under the curve, or ascending slope of the serum response curve. Examination of factors besides age group that may have accounted for these results suggests that the serum response of the elderly may be more a function of body composition and/or serum lipid patterns than of age per se. However, in the present US population, it may not be valid to control for these factors, which are both closely related to aging.     

Circulating ALT Levels in Healthy Volunteers Over Life-Span: Assessing Aging Paradox and Nutritional Implications

Abstract

Background: Two facts are generally recognized: (1) development of nonalcoholic fatty liver disease (NAFLD) is consistently linked to insulin resistance which has dietary implications and (2) circulating alanine aminotransferase (ALT) levels are reasonable markers predicting NAFLD status. In a recent cross-sectional study employing nondiabetic subjects, ALT values rose steadily within a normal range early in the life cycle but begin decreasing steadily around age 65?years.

Objectives: Because of important nutritional implications, the association between ALT levels and aging in a significantly larger population of healthy volunteers was examined for corroborative purposes. A secondary goal was to gain further knowledge concerning mechanisms behind any age-related decline in ALT activity.

Methods: Baseline data from over 10,000 physician-approved, nondiabetic subjects (age 21–84?years) of both genders who had volunteered for previous clinical investigations were assessed.

Results: In this cross-sectional examination, the line of best fit (weighted) for average yearly circulating ALT levels displayed an upward surge from ages 21 to 64?years with a discernible steady downward decline around 65?years—mimicking earlier results. Examining linear lines of correlation in the younger and older age groups, the following calculations were determined: a significant positive slope for 21 to 64?years, r?=?0.42, n?=?44, p?<?0.005, and a trending negative slope for 65 and beyond, r = ?0.43, n?=?20, p?<?0.057. Using this same datum base, the correlations between age and fasting blood glucose (FBG) mimicked the ALT results by once more showing a similar upward rise in the younger and a steady decline the older group of volunteers.

Conclusions: A paradoxical downward age-related (≥ 65?years) decline of circulating ALT coinciding with a comparable steady decrease in FBG levels was replicated in a larger population of volunteers. The close association of these two chemistries along with other findings suggest that altered glucose-insulin metabolism may participate via “survivor bias” in the ubiquitously found age-related decline of serum ALT—suggesting that nutritional measures could advance optimal health over the life-span.     

A Health Care Professional Delivered Low Carbohydrate Diet Program Reduces Body Weight,Haemoglobin A1c,Diabetes Medication Use and Cardiovascular Risk Markers—A Single-Arm Intervention Analysis

This study examined the effectiveness of a health care professional delivered low-carbohydrate diet program (Diversa Health Program) aiming to improve obesity/type-2-diabetes management for people living in Australia. 511 adults (Age:57.1 ± 13.7 [SD] yrs) who participated between January 2017–August 2021 for ≥30 days with pre-post data collected for ≥1 key outcome variable (body weight and HbA1c) were included in the analysis. Average participation duration was 218 ± 207 days with 5.4 ± 3.9 reported consultation visits. Body weight reduced from 92.3 ± 23.0 to 86.3 ± 21.1 kg (n = 506, p < 0.001). Weight loss was 0.9 ± 2.8 kg (1.3%), 4.5 ± 4.3 kg (5.7%) and 7.9 ± 7.2 kg (7.5%), respectively, for those with a classification of normal weight (n = 67), overweight (n = 122) and obese (n = 307) at commencement. HbA1c reduced from 6.0 ± 1.2 to 5.6 ± 0.7% (n = 212, p < 0.001). For members with a commencing HbA1c of <5.7% (n = 110), 5.7–6.4% (n = 55), and ≥6.5% (n = 48), HbA1c reduced −0.1 ± 0.2%, −0.3 ± 0.3%, and −1.4 ± 1.3%, respectively. For members with a commencing HbA1c ≥6.5%, 90% experienced a HbA1c reduction and 54% achieved a final HbA1c < 6.5%. With inclusion and exclusion of metformin, respectively, 124 and 82 diabetes medications were prescribed to 63 and 42 members that reduced to 82 and 35 medications prescribed to 51 and 26 members at final visit. A health care professional delivered low-carbohydrate diet program can facilitate weight loss and improve glycaemic control with greatest improvements and clinical relevance in individuals with worse baseline parameters.     

Influence of Diet and Levels of Zonulin,Lipopolysaccharide and C-Reactive Protein on Cardiometabolic Risk Factors in Young Subjects

A western diet and increased intestinal permeability may contribute to systemic inflammation and the development of cardio-metabolic alterations. The aim of this study was to assess the relationship between diet, biomarkers of intestinal permeability, and chronic low-grade inflammation on the cardiometabolic profile. A cross-sectional study was carried out in 238 young subjects aged 18–29 years, divided into two groups: with <3 cardiometabolic risk factors (CRF) and ≥3 risk factors. Anthropometric parameters, biochemical profile, and serum levels of zonulin, lipopolysaccharide (LPS), and high-sensitivity C-reactive protein (hs-CRP) were measured, and the macronutrient intake was evaluated. Interaction models showed elevated glucose levels in the presence of high biomarker levels: zonulin ≥51.6 ng/mL plus LPS ≥ 1.35 EU/mL (β = 1.1, p = 0.006), and LPS ≥1.35 EU/mL plus hs-CRP ≥ 4.3 mg/L (β = 1.2, p = 0.007). In addition, triglyceride levels increased in the presence of LPS ≥ 1.35 EU/mL and hs-CRP ≥ 4.3 mg/L (β = 3.9, p = 0.01). Despite having increased biomarker levels, a higher consumption of water (≥2100 mL), polyunsaturated fatty acids (≥6.0 g), or fiber (≥30 g) decreased triglyceride (β = −9.6, p = 0.03), total cholesterol (β = −5.1, p = 0.01), and LDL-C levels (β = −7.7, p = 0.01). These findings suggest that the increased consumption of water, PUFA and fiber may improve lipid profile in subjects with intestinal permeability dysfunction or low-grade systemic inflammation.     

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30–40 years, who were randomly assigned to two groups—a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.     

Differential Development of Glucose Intolerance and Pancreatic Islet Adaptation in Multiple Diet Induced Obesity Models

Background: The C57BL/6 mouse fed a high fat diet is a common and valuable model in experimental studies of obesity and type 2 diabetes (T2D). Different high fat diets are used and in order to determine which diet produces a model most accurately resembling human T2D, they need to be compared head-to-head. Methods: Four different diets, the 60% high fat diet (HFD) and the 58% high fat-high sucrose Surwit diet (HFHS) and their respective controls, were compared in C57BL/6J mice using glucose tolerance tests (IVGTT) and the euglycemic clamp. Results: Mice fed a HFD gained more weight than HFHS fed mice despite having similar energy intake. Both high fat diet models were glucose intolerant after eight weeks. Mice fed the HFD had elevated basal insulin, which was not seen in the HFHS group. The acute insulin response (AIR) was unchanged in the HFD group, but slightly increased in the HFHS diet group. The HFHS diet group had a threefold greater total insulin secretion during the IVGTT compared to its control, while no differences were seen in the HFD group. Insulin sensitivity was decreased fourfold in the HFD group, but not in the HFHS diet group. Conclusion: The HFD and HFHS diet models show differential effects on the development of insulin resistance and beta cell adaptation. These discrepancies are important to acknowledge in order to select the appropriate diet for specific studies.     

Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss,Glucose Metabolism,Insulin Kinetics and β-Cell Function in Morbidly Obese Individuals

Low-calorie Mediterranean-style or low-carbohydrate dietary regimens are widely used nutritional strategies against obesity and associated metabolic diseases, including type 2 diabetes. The aim of this study was to compare the effectiveness of a balanced Mediterranean diet with a low-carbohydrate diet on weight loss and glucose homeostasis in morbidly obese individuals at high risk to develop diabetes. Insulin secretion, insulin clearance, and different β-cell function components were estimated by modeling plasma glucose, insulin and C-peptide profiles during 75-g oral glucose tolerance tests (OGTTs) performed at baseline and after 4 weeks of each dietary intervention. The average weight loss was 5%, being 58% greater in the low-carbohydrate-group than Mediterranean-group. Fasting plasma glucose and glucose tolerance were not affected by the diets. The two dietary regimens proved similarly effective in improving insulin resistance and fasting hyperinsulinemia, while enhancing endogenous insulin clearance and β-cell glucose sensitivity. In summary, we demonstrated that a low-carbohydrate diet is a successful short-term approach for weight loss in morbidly obese patients and a feasible alternative to the Mediterranean diet for its glucometabolic benefits, including improvements in insulin resistance, insulin clearance and β-cell function. Further studies are needed to compare the long-term efficacy and safety of the two diets.