Sex differences in adipose insulin resistance are linked to obesity, lipolysis and insulin receptor substrate 1.

BACKGROUND/OBJECTIVE: Insulin resistance is more prominent in men than women. If this involves adipose tissue is unknown and was presently examined. SUBJECTS/METHODS: AdipoIR (in vivo adipose insulin resistance index) was measured in 2344 women and 787 men. In 259 of the women and 54 of the men, insulin induced inhibition of lipolysis (acylglycerol breakdown) and stimulation of lipogenesis (glucose conversion to acylglycerols) were determined in subcutaneous adipocytes; in addition, basal (spontaneous) lipolysis was also determined in the fat cells. In 234 women and 115 men, RNAseq expression of canonical insulin signal genes were measured in subcutaneous adipose tissue. Messenger RNA transcripts of the most discriminant genes were quantified in 175 women and 109 men. RESULTS: Men had higher AdipoIR values than women but only when obesity (body mass index 30 kg/m2 or more) was present (p < 0.0001). The latter sex dimorphism was found among physically active and sedentary people, in those with and without cardiometabolic disease and in people using nicotine or not (p = 0.0003 or less). In obesity, adipocyte insulin sensitivity (half maximum effective hormone concentration) and maximal antilipolytic effect were tenfold and 10% lower, respectively, in men than women (p = 0.005 or less). Basal rate of lipolysis was two times higher in men than women (p > 0.0001). Sensitivity and maximum effect of insulin on lipogenesis were similar in both sexes (p = 0.26 and p = 0.18, respectively). When corrected for multiple comparison only RNAseq expression of insulin receptor substrate 1 (IRS1) was lower in men than women (p < 0.0001). The mRNA transcript for IRS1 was 60% higher in women than men (p < 0.0001). CONCLUSIONS: In obesity, adipose tissue insulin resistance is more pronounced in men than in women. The mechanism involves less efficient insulin-mediated inhibition of adipocyte lipolysis, increased basal rate of lipolysis and decreased adipose expression of a key element of insulin signaling, IRS1.

Post-intervention Adherence to the New Nordic Renal Diet among patients with chronic kidney disease, stages 3 and 4.

The New Nordic Renal Diet (NNRD) is a meal pattern reduced in phosphorus, protein, and sodium for patients with moderate chronic kidney disease. The NNRD showed improvements in metabolic, and physiological outcomes after 26-weeks intervention. In the original study, participants were randomized to NNRD (n = 30), or control (habitual diet) (n = 30). The aim of this study was to explore adherence to the NNRD 3 months after cessation of intervention (follow-up). Fifty-seven participants completed the follow-up visit, which consisted of fasting blood samples and 24 h urine samples. At follow-up, there was no longer a significant reduction in 24 h urine phosphorus excretion in the NNRD group. From intervention to follow-up, 24 h urine phosphorus increased by 63 mg in the NNRD group, vs. -24.1 mg in the control group, between-group difference 87.1 mg (-10.1, 184.3, p = 0.08). Our findings show that more active intervention is needed to support adherence and maintain beneficial effects of the NNRD.

Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Risk assessment of nutrients: There must be a threshold for their effects.

Nutrients serve physiological functions in a dose-dependent manner and that needs to be recognized in risk assessment. An example of the consequences of not properly considering this can be seen in a recent assessment by the European Food Safety Authority (EFSA). EFSA concluded in 2022 that the intake of added and free sugars should be "as low as possible in the context of a nutritionally adequate diet". That conclusion of EFSA is based on the effects on two surrogate endpoints for an adverse effect found in randomized controlled trials with high sugars intake levels: fasting glucose and fasting triglycerides. The lowest intake levels in these trials were around 10 energy% and at this intake level there were no adverse effects on the two outcomes. This indicates that the adverse effects of sugars have an observable threshold value for these two endpoints. The most appropriate interpretation from the vast amount of data is that currently no definitive conclusion can be drawn on the tolerable upper intake level for dietary sugars. Therefore, EFSA's own guidance would lead to the conclusion that the available data do not allow the setting of an upper limit for added sugars and hence, that more robust data are required to identify the threshold value for intake of sugars.

A high protein low glycemic index diet has no adverse effect on blood pressure in pregnant women with overweight or obesity: a secondary data analysis of a randomized clinical trial.

Objectives: The objective of this analysis was to evaluate the effect of a diet rich in animal protein and low in glycemic index on blood pressure during pregnancy. Design: This post hoc, secondary data analysis of a randomized controlled trial, evaluated blood pressure in pregnant participants who were randomized either to an ad libitum diet with high protein and low glycemic index, rich in dairy and seafood, or an ad libitum control diet according to national recommendations. Setting: The study occurred in pregnant women in Copenhagen, Denmark. Sample: A total of 279 pregnant females with overweight or obesity were enrolled. Methods and outcome measure: Blood pressure was measured at 5 timepoints during pregnancy from gestational week 15 through week 36, and blood pressure between groups was compared. Results: There were no differences between diet arms in systolic or diastolic blood pressure over time. There were also no differences in most blood-pressure-related pregnancy complications, including the prevalence of premature birth, preeclampsia, or hypertension, but the frequency of total cesarean sections was lower in the active than the control group (16 out of 104 vs. 30 out of 104) (p = 0.02). Conclusion: Increased animal protein intake was not associated with changes in blood pressure in pregnant women with overweight or obesity. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT01894139].

Health effects of the New Nordic Renal Diet in patients with stage 3 and 4 chronic kidney disease, compared with habitual diet: a randomized trial.

BACKGROUND: Chronic kidney disease (CKD) leads to an accumulation of waste products and causes adverse cardiometabolic effects. OBJECTIVES: We investigated the health effects of the New Nordic Renal Diet (NNRD), a novel meal pattern reduced in phosphorus, protein, and sodium. METHODS: A 26-wk randomized trial compared the NNRD with a habitual diet. The NNRD group received weekly home deliveries of food and recipes. Monthly study visits included fasting blood samples, 24-h urine samples, blood pressure, and anthropometric measurements. Intention-to-treat analysis used linear mixed-effects models. RESULTS: Sixty patients, mean estimated glomerular filtration rate (eGFR) 34 mL/min/1.73 m2 and body mass index of 25-27 kg/m2, were included and 58 completed. Metabolic syndrome was present in 53% (NNRD group) and 57% (control group). The NNRD group (n = 30) reduced their 24-h urine phosphorus excretion by 19% (-153 mg; 95% confidence interval [CI]: -210, -95), control group (n = 30) (no change), between-group difference -171 mg (95% CI: -233, -109; P < 0.001). Proteinuria was reduced by 39% in the NNRD group (-0.33 g/d; 95% CI: -0.47, -0.18), control group (no change), between-group difference -0.34 g/d (95% CI: -0.52, -0.17; P < 0.001). Plasma urea was reduced by -1.5 mmol/L in the NNRD group (95% CI: -2.1, -0.9), control group (no change), between-group difference -1.4 mmol/L (95% CI: -2.0, -0.7; P < 0.001). Systolic blood pressure fell by -5.2 mmHg in the NNRD group (95% CI: -8.4, -2.1), control group (no change), between-group difference -3.9 mmHg (95% CI; -7.6, -0.2; P = 0.04). The NNRD group lost -1.7 kg (95% CI: -2.6, -0.8), control group (no change), between-group difference -2.0 kg (95% CI: -3.0, -1.0; P < 0.001). There were no effects on eGFR during the 26-wk intervention. CONCLUSION: NNRD in moderate CKD reduces phosphorus excretion, proteinuria, systolic blood pressure, and weight, mainly by reducing abdominal fat. This trial was registered at clinicaltrials.gov as NCT04579315.

Predicting weight loss success on a new Nordic diet: an untargeted multi-platform metabolomics and machine learning approach.

Background and aim: Results from randomized controlled trials indicate that no single diet performs better than other for all people living with obesity. Regardless of the diet plan, there is always large inter-individual variability in weight changes, with some individuals losing weight and some not losing or even gaining weight. This raises the possibility that, for different individuals, the optimal diet for successful weight loss may differ. The current study utilized machine learning to build a predictive model for successful weight loss in subjects with overweight or obesity on a New Nordic Diet (NND). Methods: Ninety-one subjects consumed an NND ad libitum for 26 weeks. Based on their weight loss, individuals were classified as responders (weight loss ≥5%, n = 46) or non-responders (weight loss <2%, n = 24). We used clinical baseline data combined with baseline urine and plasma untargeted metabolomics data from two different analytical platforms, resulting in a data set including 2,766 features, and employed symbolic regression (QLattice) to develop a predictive model for weight loss success. Results: There were no differences in clinical parameters at baseline between responders and non-responders, except age (47 ± 13 vs. 39 ± 11 years, respectively, p = 0.009). The final predictive model for weight loss contained adipic acid and argininic acid from urine (both metabolites were found at lower levels in responders) and generalized from the training (AUC 0.88) to the test set (AUC 0.81). Responders were also able to maintain a weight loss of 4.3% in a 12 month follow-up period. Conclusion: We identified a model containing two metabolites that were able to predict the likelihood of achieving a clinically significant weight loss on an ad libitum NND. This work demonstrates that models based on an untargeted multi-platform metabolomics approach can be used to optimize precision dietary treatment for obesity.

Harnessing the Magic of the Dairy Matrix for Next-Level Health Solutions: A Summary of a Symposium Presented at Nutrition 2022.

An emerging body of scientific evidence demonstrates that the food matrix-the interaction among nutrients, bioactive components, and physical structure of a food-can affect health in significant, unexpected ways beyond its individual nutrients. In particular, research suggests that consumption of dairy foods such as milk, yogurt, and cheese may affect human health in a matrix-dependent fashion. To disseminate and discuss the growing body of evidence surrounding the role of the dairy food matrix on cardiometabolic health, 3 expert researchers on the topic of the food matrix shared the latest science in a session entitled "Next-Level Health Solutions: The Magic of the Matrix" at the American Society for Nutrition's 2022 LIVE ONLINE Conference. This article is a summary of the literature presented and discussed during that session. A substantial body of literature demonstrates that full-fat dairy foods, particularly fermented dairy foods, may beneficially modulate cardiometabolic outcomes depending on an individual's health status. These findings have important implications for current authoritative dietary guidance that recommends the consumption of low-fat or fat-free dairy foods. Furthermore, this evidence may inform practical applications of harnessing dairy's unique profile of bioactives for health promotion and disease prevention at the individual and community levels.

Human blood plasma biomarkers of diet and weight loss among centrally obese subjects in a New Nordic Diet intervention.

Scope: The New Nordic Diet (NND) has been shown to promote weight loss and lower blood pressure amongst obese people. This study investigates blood plasma metabolite and lipoprotein biomarkers differentiating subjects who followed Average Danish Diet (ADD) or NND. The study also evaluates how the individual response to the diet is reflected in the metabolic differences between NND subjects who lost or maintained their pre-intervention weight. Methods: Centrally obese Danes (BMI >25) followed NND (90 subjects) or ADD (56 subjects) for 6 months. Fasting blood plasma samples, collected at three time-points during the intervention, were screened for metabolites and lipoproteins (LPs) using proton nuclear magnetic resonance spectroscopy. In total, 154 metabolites and 65 lipoproteins were analysed. Results: The NND showed a relatively small but significant effect on the plasma metabolome and lipoprotein profiles, with explained variations ranging from 0.6% for lipoproteins to 4.8% for metabolites. A total of 38 metabolites and 11 lipoproteins were found to be affected by the NND. The primary biomarkers differentiating the two diets were found to be HDL-1 cholesterol, apolipoprotein A1, phospholipids, and ketone bodies (3-hydroxybutyric acid, acetone, and acetoacetic acid). The increased levels of ketone bodies detected in the NND group inversely associated with the decrease in diastolic blood pressure of the NND subjects. The study also showed that body weight loss among the NND subjects was weakly associated with plasma levels of citrate. Conclusion: The main plasma metabolites associated with NND were acetate, methanol and 3-hydroxybutyrate. The metabolic changes associated with the NND-driven weight loss are mostly pronounced in energy and lipid metabolism.

Prevention and management of obesity in a lifetime perspective.

The prevalence of obesity is increasing across all geographies. Obesity develops due to a disruption of the energy balance regulation. However, the cause is not well understood. Identification of causal factors that may be modified is crucial to reduce the prevalence of obesity. However, the interventions needed will likely differ between life stages. Hence, obesity research should span from pre-conception to adulthood. In this review, we point to gaps and limitations in existing research, highlight recently initiated studies from which we are awaiting results and point to future directions.

Gestational weight gain in women with pre-pregnancy overweight or obesity and anthropometry of infants at birth.

Objective: To examine the association of gestational weight gain (GWG) among women with pre-pregnancy overweight or obesity with infant weight and BMI z-score at birth. Methods: This study is a secondary analysis of a randomized controlled trial including data from 208 infants at birth born by mothers with pre-pregnancy BMI between 28 and 45 kg/m2 who completed the APPROACH study (randomized to a high-protein low-glycemic index diet or a moderate-protein moderate-glycemic index diet). This analysis pooled the two diet treatment groups together and data were analyzed using a linear mixed model. Results: Limiting GWG by 1 kg was associated with lower birthweight (-16 g, P = 0.003), BMI z-score (-0.03SD, P = 0.019), weight z-score (-0.03SD, P = 0.004), and infant abdominal circumference (-0.06 cm, P = 0.039). Infants born by mothers whose GWG was ≤9 kg weighed less (122 g, 95% CI: 6-249, P = 0.040), had similar BMI z-score (0.2SD, 95% CI: -0.06 to 0.55, P = 0.120), and lower incidence of emergency cesarean deliveries (11.5% vs. 23.1%, P = 0.044) compared to infants born by mothers whose GWG was >9 kg. When women were classified into GWG quartiles, women in Q1 (GWG range: -7.0 to 3.2 kg) gave birth to smaller infants (3,420 g, P = 0.015) with lower BMI z-score (-0.5SD, P = 0.041) than women in Q2 (3.3-7.1 kg), Q3 (7.2-10.9 kg) and Q4 (11.1-30.2 kg). Conclusions: Limiting GWG among women with pre-pregnancy overweight or obesity was associated with lower infant weight, BMI z-score, weight z-score, and abdominal circumference at birth. Moreover, GWG below the Institute of Medicine guideline of a maximum of 9 kg was associated with lower birthweight and fewer emergency cesarean deliveries.

Weight loss relapse associated with exposure to perfluorinated alkylate substances.

OBJECTIVE: The purpose of this study was to test the hypothesis that perfluorinated alkylate substance (PFAS) exposures are associated with body weight increases in a dietary intervention study. METHODS: In the DioGenes trial, adults with obesity first lost at least 8% of their body weight and then completed at least 26 weeks on a specific diet. Concentrations of five major PFASs were assessed in plasma samples from study baseline. RESULTS: In 381 participants with complete data, plasma concentrations averaged 2.9 ng/mL and 1.0 ng/mL for perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), respectively. A doubling in plasma PFOA was associated with an increase in weight at 26 weeks by 1.50 kg (95% CI: 0.88-2.11), with an increase of 0.91 kg (95% CI: 0.54-1.27) for PFHxS, independent of diet groups and sex. Associations for other PFASs were in the same direction and significant, although not after adjustment for PFOA and PFHxS. Weight changes associated with elevated PFAS exposures were similar to or larger than average changes ascribed to the different diet groups. CONCLUSIONS: Elevated plasma concentrations of PFOA and PFHxS were associated with increased weight gain that exceeded those related to the diets. Obesogenic PFASs may cause weight gain and thus contribute to the obesity pandemic.

Baseline gene expression in subcutaneous adipose tissue predicts diet-induced weight loss in individuals with obesity.

Background: Weight loss effectively reduces cardiometabolic health risks among people with overweight and obesity, but inter-individual variability in weight loss maintenance is large. Here we studied whether baseline gene expression in subcutaneous adipose tissue predicts diet-induced weight loss success. Methods: Within the 8-month multicenter dietary intervention study DiOGenes, we classified a low weight-losers (low-WL) group and a high-WL group based on median weight loss percentage (9.9%) from 281 individuals. Using RNA sequencing, we identified the significantly differentially expressed genes between high-WL and low-WL at baseline and their enriched pathways. We used this information together with support vector machines with linear kernel to build classifier models that predict the weight loss classes. Results: Prediction models based on a selection of genes that are associated with the discovered pathways 'lipid metabolism' (max AUC = 0.74, 95% CI [0.62-0.86]) and 'response to virus' (max AUC = 0.72, 95% CI [0.61-0.83]) predicted the weight-loss classes high-WL/low-WL significantly better than models based on randomly selected genes (P < 0.01). The performance of the models based on 'response to virus' genes is highly dependent on those genes that are also associated with lipid metabolism. Incorporation of baseline clinical factors into these models did not noticeably enhance the model performance in most of the runs. This study demonstrates that baseline adipose tissue gene expression data, together with supervised machine learning, facilitates the characterization of the determinants of successful weight loss.

An integrated single cell and spatial transcriptomic map of human white adipose tissue.

To date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.

Physical Activity and Insulin Sensitivity Independently Attenuate the Effect of FTO rs9939609 on Obesity.

OBJECTIVE: The association between FTO rs9939609 and obesity is modified by physical activity (PA) and/or insulin sensitivity (IS). We aimed to assess whether these modifications are independent, to assess whether PA and/or IS modify the association between rs9939609 and cardiometabolic traits, and to elucidate underlying mechanisms. RESEARCH DESIGN AND METHODS: Genetic association analyses comprised up to 19,585 individuals. PA was self-reported, and IS was defined based on inverted HOMA insulin resistance index. Functional analyses were performed in muscle biopsies from 140 men and in cultured muscle cells. RESULTS: The BMI-increasing effect of the FTO rs9939609 A allele was attenuated by 47% with high PA (ß [SE], -0.32 [0.10] kg/m2, P = 0.0013) and by 51% with high IS (-0.31 [0.09] kg/m2, P = 0.00028). Interestingly, these interactions were essentially independent (PA, -0.20 [0.09] kg/m2, P = 0.023; IS, -0.28 [0.09] kg/m2, P = 0.0011). The rs9939609 A allele was also associated with higher all-cause mortality and certain cardiometabolic outcomes (hazard ratio, 1.07-1.20, P > 0.04), and these effects tended to be weakened by greater PA and IS. Moreover, the rs9939609 A allele was associated with higher expression of FTO in skeletal muscle tissue (0.03 [0.01], P = 0.011), and in skeletal muscle cells, we identified a physical interaction between the FTO promoter and an enhancer region encompassing rs9939609. CONCLUSIONS: Greater PA and IS independently reduced the effect of rs9939609 on obesity. These effects might be mediated through altered expression of FTO in skeletal muscle. Our results indicated that PA and/or other means of increasing insulin sensitivity could counteract FTO-related genetic predisposition to obesity.

The New Nordic Renal Diet Induces a Pronounced Reduction of Urine Acid Excretion and Uremic Toxins in Chronic Kidney Disease Patients (Stage 3 and 4).

OBJECTIVE: Metabolic acidosis and the uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with increased risks of kidney disease progression, muscle catabolism, cardiovascular disease, and mortality in patients with chronic kidney disease (CKD). The New Nordic Renal Diet (NNRD) is a plant-focused meal pattern, with reduced phosphorus and protein content compared to an average Danish diet. Due to a higher amount of plant-based products, we hypothesized that NNRD would reduce renal excretion of acids and uremic toxins. Thus, we evaluated the effects of NNRD on metabolic acidosis and uremic toxins in patients with moderate CKD, stages 3-4. DESIGN AND METHODS: This post hoc analysis is based on a randomized controlled crossover trial comparing 1 week of the NNRD to a control 1-week period of an average Danish diet, in patients with CKD stages 3 and 4. Urine pH and urine excretion of bicarbonate, ammonium, titratable acids, IS, and PCS alongside plasma total CO2 (tCO2) were measured at days 1, 4, and 7 in 18 patients. RESULTS: After 7 days on NNRD 24-hour urine net acid excretion was decreased by 80% (P < .001), 24-hour urine excretion of ammonium and bicarbonate decreased by 34% (P < .001), and increased by 678% (P < .001), respectively, compared with the control period. Plasma tCO2 was increased by 8% (P = .005). Moreover, 24-hour urine excretion of PCS and IS were reduced by 31% (P = .018) and 29% (P < .001), respectively. CONCLUSION: One week of NNRD in patients suffering from moderate CKD effectively improved metabolic acidosis with a marked reduction in urine net acid excretion that included a large increase in urine bicarbonate excretion. In addition, NNRD reduced urinary excretion of the uremic toxins PCS and IS. These results encourage further investigations of the long-term effects of NNRD on renal protection in patients with CKD.

Effects of Carbohydrate Restriction on Body Weight and Glycemic Control in Individuals with Type 2 Diabetes: A Randomized Controlled Trial of Efficacy in Real-Life Settings.

A fully provided, hypocaloric, carbohydrate-reduced high-protein (CRHP) diet compared to a hypocaloric conventional diabetes (CD) diet for 6 weeks improved glycemic control to a greater extent in face of an intended 6% weight loss in individuals with type 2 diabetes mellitus (T2DM). The present 24-week extension of that study reports on the efficacy of CRHP and CD diets in a real-life setting. Sixty-five individuals with T2DM who completed the initial 6-week fully provided diet period (% energy from carbohydrate, protein, and fat was 30/30/40 in CRHP, and 50/17/33 in CD) continued a free-living, dietician guided 24-week period of which 59 individuals completed. The CRHP compared to CD group reported a 4% lower carbohydrate intake and had higher urea excretion by 22% (both p ≤ 0.05) at week 30, suggesting less difference in carbohydrate and protein intake between groups during the 24-week extension compared to week 6. The loss of body weight during the initial 6 weeks was maintained in both groups during the 24-week extension (-5.5 ± 4.5 and -4.6 ± 4.8 kg) as well as HbA1c (-8.4 ± 6.2 and -8.4 ± 6.9 mmol/mol) with no significant differences between groups. The additional benefits on glucoregulation harnessed by carbohydrate restriction under full diet provision for 6 weeks combined with titrated weight loss could not be maintained in a real-life setting of self-prepared diet aiming on similar diets for 6 months.

Susceptibility of Human Plasma N-glycome to Low-Calorie and Different Weight-Maintenance Diets.

Aberrant plasma protein glycosylation is associated with a wide range of diseases, including diabetes, cardiovascular, and immunological disorders. To investigate plasma protein glycosylation alterations due to weight loss and successive weight-maintenance diets, 1850 glycomes from participants of the Diogenes study were analyzed using Ultra-High-Performance Liquid Chromatography (UHPLC). The Diogenes study is a large dietary intervention study in which participants were subjected to a low-calorie diet (LCD) followed by one of five different weight-maintenance diets in a period of 6 months. The most notable alterations of the plasma glycome were 8 weeks after the subjects engaged in the LCD; a significant increase in low-branched glycan structures, accompanied by a decrease in high-branched glycan structures. After the LCD period, there was also a significant rise in N-glycan structures with antennary fucose. Interestingly, we did not observe significant changes between different diets, and almost all effects we observed immediately after the LCD period were annulled during the weight-maintenance diets period.

Impact of a Weight-Loss Rehabilitation Program on Sleep Apnea Risk and Subjective Sleepiness in Patients with Overweight/Obesity: The DietSleep Study.

Obstructive sleep apnea (OSA) is one of the most frequent chronic diseases, and comorbid obesity occurs in more than 60% of cases. Variations in body weight influence both OSA severity and OSA-related symptoms. We prospectively assessed the impact of a weight-loss program using the Berlin score to reflect OSA risk, and we also used the Epworth Sleepiness Scale (ESS) to assess daytime sleepiness. DietSleep was a prospective multicentric cohort study investigating OSA risk and daytime sleepiness before and after weight-loss intervention. One hundred and twenty-seven patients were included (initial OSA risk 36%), most of whom were women (85.8%) with a median body mass index (BMI) of 29.7 kg/m2, and the interquartile range was (27.6; 34). The diet-based weight-loss program induced a median decrease in BMI of 3.7 kg/m2 (−5; −2.9) (body weight~12.1% (−16.0; −8.8)) over a period of 171 days (114; 269). Changes in anthropometric values were similar regarding OSA risk after adjusting for initial values. Berlin scores significantly improved from 3 (1; 5) to 1 (0; 2), p < 0.01; the proportion of patients with a Berlin score ≥2 decreased from 36% to 7% after the intervention. The proportion of patients with ESS ≥11 decreased from 13% to 2%. These results confirm that a weight-loss program produces clinically relevant weight loss and a significant improvement in both OSA and subjective daytime sleepiness.