Dietary modifications are crucial for managing newly diagnosed type 2 diabetes mellitus (T2DM) and preventing its health complications, but many patients fail to achieve clinical goals with diet ...alone. We sought to evaluate the clinical effects of a personalized postprandial-targeting (PPT) diet on glycemic control and metabolic health in individuals with newly diagnosed T2DM as compared to the commonly recommended Mediterranean-style (MED) diet.
We enrolled 23 adults with newly diagnosed T2DM (aged 53.5 ± 8.9 years, 48% males) for a randomized crossover trial of two 2-week-long dietary interventions. Participants were blinded to their assignment to one of the two sequence groups: either PPT-MED or MED-PPT diets. The PPT diet relies on a machine learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses (PPGR). We further evaluated the long-term effects of PPT diet on glycemic control and metabolic health by an additional 6-month PPT intervention (n = 16). Participants were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using a smartphone application.
In the crossover intervention, the PPT diet lead to significant lower levels of CGM-based measures as compared to the MED diet, including average PPGR (mean difference between diets, - 19.8 ± 16.3 mg/dl × h, p < 0.001), mean glucose (mean difference between diets, - 7.8 ± 5.5 mg/dl, p < 0.001), and daily time of glucose levels > 140 mg/dl (mean difference between diets, - 2.42 ± 1.7 h/day, p < 0.001). Blood fructosamine also decreased significantly more during PPT compared to MED intervention (mean change difference between diets, - 16.4 ± 37 μmol/dl, p < 0.0001). At the end of 6 months, the PPT intervention leads to significant improvements in multiple metabolic health parameters, among them HbA1c (mean ± SD, - 0.39 ± 0.48%, p < 0.001), fasting glucose (- 16.4 ± 24.2 mg/dl, p = 0.02) and triglycerides (- 49 ± 46 mg/dl, p < 0.001). Importantly, 61% of the participants exhibited diabetes remission, as measured by HbA1c < 6.5%. Finally, some clinical improvements were significantly associated with gut microbiome changes per person.
In this crossover trial in subjects with newly diagnosed T2DM, a PPT diet improved CGM-based glycemic measures significantly more than a Mediterranean-style MED diet. Additional 6-month PPT intervention further improved glycemic control and metabolic health parameters, supporting the clinical efficacy of this approach.
ClinicalTrials.gov number, NCT01892956.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background/Aims Weight loss is considered therapeutic for patients with NAFLD. However, there is no epidemiological evidence that dietary habits are associated with NAFLD. Dietary patterns associated ...with primary NAFLD were investigated. Methods A cross-sectional study of a sub-sample ( n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound, biochemical tests, dietary and anthropometric evaluations. A semi-quantitative food-frequency questionnaire was administered. Results After exclusion, 349 volunteers (52.7% male, mean age 50.7 ± 10.4, 30.9% primary NAFLD) were included. The NAFLD group consumed almost twice the amount of soft drinks ( P = 0.03) and 27% more meat ( P < 0.001). In contrast, the NAFLD group consumed somewhat less fish rich in omega-3 ( P = 0.056). Adjusting for age, gender, BMI and total calories, intake of soft drinks and meat was significantly associated with an increased risk for NAFLD (OR = 1.45, 1.13–1.85 95% CI and OR = 1.37, 1.04–1.83 95% CI, respectively). Conclusions NAFLD patients have a higher intake of soft drinks and meat and a tendency towards a lower intake of fish rich in omega-3. Moreover, a higher intake of soft drinks and meat is associated with an increased risk of NAFLD, independently of age, gender, BMI and total calories.
Background & Aims Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLD’s epidemiology in ...prospective follow-up of individuals sampled from the general population. Methods Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. Results Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8 ± 6.1 vs. 1.4 ± 5.5 kg, p <0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7 years. Weight loss of 2.7 ± 5.0 kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. Conclusions Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.
Summary Background Although colonoscopy is the accepted standard for detection of colorectal adenomas and cancers, many adenomas and some cancers are missed. To avoid interval colorectal cancer, the ...adenoma miss rate of colonoscopy needs to be reduced by improvement of colonoscopy technique and imaging capability. We aimed to compare the adenoma miss rates of full-spectrum endoscopy colonoscopy with those of standard forward-viewing colonoscopy. Methods We did an international, multicentre, randomised trial at three sites in Israel, one site in the Netherlands, and two sites in the USA between Feb 1, 2012, and March 31, 2013. Patients aged 18–70 years referred for colorectal cancer screening, polyp surveillance, or diagnostic assessment underwent same-day, back-to-back tandem colonoscopy with standard forward-viewing colonoscope and the full-spectrum endoscopy colonoscope. The patients were randomly assigned (1:1), via computer-generated randomisation with block size of 20, to which procedure was done first. The endoscopist was masked to group allocation until immediately before the start of colonoscopy examinations; patients were not masked. The primary endpoint was adenoma miss rates. We did per-protocol analyses. This trial is registered with ClinicalTrials.gov , number NCT01549535. Findings 197 participants were enrolled. 185 participants were included in the per-protocol analyses: 88 (48%) were randomly assigned to receive standard forward-viewing colonoscopy first, and 97 (52%) to receive full-spectrum endoscopy colonoscopy first. By per-lesion analysis, the adenoma miss rate was significantly lower in patients in the full-spectrum endoscopy group than in those in the standard forward-viewing procedure group: five (7%) of 67 vs 20 (41%) of 49 adenomas were missed (p<0·0001). Standard forward-viewing colonoscopy missed 20 adenomas in 15 patients; of those, three (15%) were advanced adenomas. Full-spectrum endoscopy missed five adenomas in five patients in whom an adenoma had already been detected with first-pass standard forward-viewing colonoscopy; none of these missed adenomas were advanced. One patient was admitted to hospital for colitis detected at colonoscopy, whereas five minor adverse events were reported including vomiting, diarrhoea, cystitis, gastroenteritis, and bleeding. Interpretation Full-spectrum endoscopy represents a technology advancement for colonoscopy and could improve the efficacy of colorectal cancer screening and surveillance. Funding EndoChoice.
AIM:To evaluate the effect of resistance training(RT)on non alcoholic liver disease(NAFLD)patients.METHODS:A randomized clinical trial enrolling NAFLD patients without secondary liver ...disease(e.g.,without hepatitis B virus,hepatitis C virus or excessive alcohol consumption).Patients were randomly allocated either to RT,three times weekly,for 3 mo or a control arm consisting of home stretching.The RT included leg press,chest press,seated rowing,latissimus pull down etc.with 8-12 repetitions,3 sets for each exercise,for a total duration of 40 min.Hepatic ultrasound,fasting blood tests,anthropometrics and body composition by dual energy X-ray absorptiometry were assessed.At baseline and follow-up,patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake.Steatosis was quantified by the hepatorenal-ultrasound index(HRI)representing the ratio between the brightness level of the liver and the right kidney.The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy.RESULTS:Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching.After dropout or exclusion from analysis because of protocol violation(weight change>3 kg),thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol.All baseline characteristics were similar for the two treatment groups with respect to demographics,anthropometrics and body composition,blood tests and liver steatosis on imaging.HRI score was reduced significantly in the RT arm as compared to the stretching arm(-0.25±0.37 vs-0.05±0.28,P=0.017).The RT arm had a significantly higher reduction in total,trunk and android fat with increase in lean body mass.There was no correlation between the reduction in HRI in the RT arm and weight change during the study,but it was positively correlated with the change in trunk fat(r=0.37,P=0.048).The RT arm had a significant reduction in serum ferritin and total cholesterol.There was no significant difference between arms in dietary changes and these did not correlate with HRI change.CONCLUSION:Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin.RT may serve as a complement to treatment of NAFLD.
Background and Aims The self-propelled disposable colonoscope (SPDC) with a 360° view is designed to enhance visualization, minimize risks of perforation and infection transmission, and shorten ...operator training time associated with conventional colonoscopy (CC). We evaluated SPDC efficacy for cecal intubation and safety. Methods Prospective patients presenting for colorectal cancer screening underwent SPDC immediately followed by CC. Initial patients necessary for SPDC operators to achieve proficiency comprised the training cohort. Subsequent enrolled patients comprised the study cohort. SPDC colonoscopy was performed up to the cecum, where anatomic landmarks were photographed and mucosal suction marks were placed. During SPDC withdrawal, polyps were recorded and similarly marked. On the second pass (by using CC), any potential mucosal damage and suction marks from the SPDC as well as polyps were recorded. Main endpoints included SPDC cecal intubation rates, confirmed by anatomic landmarks and residual marks seen on subsequent CC, and frequency and severity of adverse events and mucosal damage with SPDC. The secondary endpoint was subjective procedure proficiency, evaluated by the operator based on the training cohort. The tertiary endpoint was documenting pathologies visualized with SPDC. Results Fifty-six of 58 enrolled subjects completed the study. Proficiency with SPDC was attained after 8 to 10 procedures. Cecal intubation was successful in 98.2% (55/56 subjects; 95% confidence interval CI, 90.4%-99.9%), including 100% (95% CI, 90.7%-100%) of the study cohort and 94.4% (95% CI, 72.7%-99.9%) of the training cohort. No mucosal damage or adverse events were reported. SPDC detected 87.5% of polyps seen in tandem CC, including all polyps larger than 5 mm. Conclusions SPDC was highly successful, simple to use, and safe in achieving complete colonoscopy (cecal intubation). (Clinical trial registration number: 0692-12-TLV .)
Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study ...was to examine the association between PA and NAFLD. We conducted a cross‐sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty‐nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P ≤ 0.03). The SteatoTest was significantly lower among subjects engaging in any PA or resistance PA at least once a week (P ≤ 0.01). PA at least once a week in all categories was associated with a reduced risk for abdominal obesity. Adjusting for sex, engaging in any kind of sports (odds ratio OR 0.66, 95% confidence interval CI 0.44‐0.96 per 1 standard deviation increment in PA score) and resistance exercise (OR 0.61, 95% CI 0.38‐0.85) were inversely associated with NAFLD. These associations remained unchanged after adjusting for homeostasis model assessment, most nutritional factors, adiponectin, and resistin. Only the association with resistance PA remained significant with further adjustment for body mass index (OR 0.61, 95% CI 0.44‐0.85). Adding leptin or waist circumference to the model eliminated the statistical significance. Conclusion: Habitual leisure‐time PA, especially anaerobic, may play a protective role in NAFLD. This association appears to be mediated by a reduced rate of abdominal obesity. (HEPATOLOGY 2008;48:1791‐1798.)
Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune ...response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin.
Colorectal-cancer (CRC) research has greatly benefited from the availability of small animal tumor models. Spontaneous and chemically-induced CRC models are widely used yet limited in their ...resemblance to human disease and are often prolonged, not accurately repetitive, and associated with inflammatory side effects. In-situ murine or human tumor implantation in the gastrointestinal tract of mice is extremely challenging, and limited by inter-animal variability and procedure-related complications and mortality. As a result, in frequent studies CRC is implanted in distal sites, most commonly the subcutaneous region, an approach that is greatly limited by the absence of normal gastrointestinal tumor milieu and has substantial effects on tumor development.
In this study we aimed to develop a well-tolerated repetitive tool to study CRC in small animals by adapting the murine colonoscopy system to serve as a platform for colonic sub-mucosal orthotopic implantation of human and murine CRC tumor cells.
We report the establishment of a novel small-animal CRC model that is minimally invasive, rapid, well-tolerated, highly reproducible, and confers precise control of tumor number, location and growth rate. Moreover, we show that this model uniquely allows the side-by-side induction of distinct genetically manipulated tumors, enabling the mechanistic study of tumor interaction and cross-talk within the native intestinal microenvironment.
Employment of this new approach may represent a major technical advance for the in-vivo study of CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin ...resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog d-Ala(2)GIP. Administration of d-Ala(2)GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, d-Ala(2)GIP reduced adipose tissue infiltration of IFN-γ-producing CD8(+) and CD4(+) T cells. Furthermore, d-Ala(2)GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-α, IL-1β, IFN-γ) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, d-Ala(2)GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR.
PDF
