Predictors of weight loss in patients with obesity treated with a Very Low-Calorie Ketogenic Diet.

Introduction: The Very Low-Calorie Ketogenic Diet (VLCKD) has emerged as a safe and effective intervention for the management of metabolic disease. Studies examining weight loss predictors are scarce and none has investigated such factors upon VLCKD treatment. Among the molecules involved in energy homeostasis and, more specifically, in metabolic changes induced by ketogenic diets, Fibroblast Growth Factor 21 (FGF21) is a hepatokine with physiology that is still unclear. Methods: We evaluated the impact of a VLCKD on weight loss and metabolic parameters and assessed weight loss predictors, including FGF21. VLCKD is a severely restricted diet (<800 Kcal/die), characterized by a very low carbohydrate intake (<50 g/day), 1.2-1.5 g protein/kg of ideal body weight and 15-30 g of fat/day. We treated 34 patients with obesity with a VLCKD for 45 days. Anthropometric parameters, body composition, and blood and urine chemistry were measured before and after treatment. Results: We found a significant improvement in body weight and composition and most metabolic parameters. Circulating FGF21 decreased significantly after the VLCKD [194.0 (137.6-284.6) to 167.8 (90.9-281.5) p < 0.001] and greater weight loss was predicted by lower baseline FGF21 (Beta = -0.410; p = 0.012), male sex (Beta = 0.472; p = 0.011), and central obesity (Beta = 0.481; p = 0.005). Discussion: VLCKD is a safe and effective treatment for obesity and obesity related metabolic derangements. Men with central obesity and lower circulating FGF21 may benefit more than others in terms of weight loss obtained following this diet. Further studies investigating whether this is specific to this diet or to any caloric restriction are warranted.

Esophageal adenocarcinoma after sleeve gastrectomy: actual or potential threat? Italian series and literature review.

BACKGROUND: Sleeve gastrectomy (SG) leads to esophageal mucosal damage in an elevated percentage of cases, configuring a clinical condition of Barrett's esophagus (BE) in a proportion as high as 15-18.8%. BE may rarely evolve into esophageal adenocarcinoma (EAC). OBJECTIVES: To raise awareness of BE as a precancerous lesion which may progress toward malignancy after this popular bariatric procedure. SETTING: Bariatric referral centers, Italy. METHODS: All patients referred to our bariatric center who developed an EAC after SG between 2012 and 2019 were reviewed and consecutively included in this study. The available scientific literature regarding this complication is additionally reviewed. RESULTS: The 3 male patients comprised in this case series underwent laparoscopic SG between 2012 and 2015 in different bariatric referral centers. Age and body mass index at baseline ranged from 21-54 years and 43.1-75.6 kg/m2, respectively. All patients were lost to follow-up early after surgery (3.7 ± 1.4 months), and were diagnosed with EAC at a mean of 27.3 ± 7.6 months after SG. The 4 reported cases in the scientific literature developed an EAC at a mean of 32.5 ± 23 months from SG. Overall, a diagnosis of EAC was made approximately 30.3 ± 17.1 months postoperatively, which seems relatively and worryingly early after surgery. CONCLUSION: Although the rate and probability of progression from BE to EAC is still not well defined, assuming that the rising popularity and execution of SG leads to a growth in the BE incidence, then the preoperative identification and stratification of cancer risk factors in this subset of patients is strongly encouraged. Clinical and endoscopic follow-ups are essential to allow for prevention and early diagnosis and for epidemiologic data collection purposes.

Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. AIM: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. METHODS: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. RESULTS: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. CONCLUSIONS: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.

Scientific evidence underlying contraindications to the ketogenic diet: An update.

First identified as a feasible treatment for intractable epilepsy, the ketogenic diet (KD) has recently gained popularity thanks to growing evidence on applications such as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and chronic pain. As with any treatment, whether pharmacologic or not, the KD might not be an appropriate intervention for every individual, and a number of contraindications have been proposed, now deeply rooted into clinical practice, excluding de facto many patients that could benefit from its use. However, many of these concerns were expressed due to the absence of clinical studies conducted on fragile populations, and an assessment of lately emerged evidence relative to KD safety is currently lacking and much needed. We herein provide a critical revision of the literature behind each safety alert, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation. Based on available evidence, the possible use of this diet as a therapeutic intervention should be assessed on a patient-to-patient basis by adequately skilled medical doctors, keeping in mind current recommendations, but reading them through the knowledge of the current state of the art.

Blueberry-Based Meals for Obese Patients with Metabolic Syndrome: A Multidisciplinary Metabolomic Pilot Study.

A pilot study was carried out on five obese/overweight patients suffering from metabolic syndrome, with the aim to evaluate postprandial effects of high fat/high glycemic load meals enriched by blueberries. Postprandial urine samples were analyzed by 1H-NMR spectroscopy after 2 and 4 h from ingestion to identify potential markers of blueberry intake. Significant decrease of methylamines, acetoacetate, acetone and succinate, known indicators of type 2 diabetes mellitus, were observed after the intake of meals enriched with blueberries. On the other hand, an accumulation of p-hydroxyphenyl-acetic acid and 3-(3'-hydroxyphenyl)-3-hydropropionic acid originating from gut microbial dehydrogenation of proanthocyanidins and procyanidins was detected. Real-time PCR-analysis of mRNAs obtained from mononuclear blood cells showed significant changes in cytokine gene expression levels after meals integrated with blueberries. In particular, the mRNAs expression of interleukin-6 (IL-6) and Transforming Growth Factor-ß (TGF-ß), pro and anti-inflammation cytokines, respectively, significantly decreased and increased after blueberry supplementation, indicating a positive impact of blueberry ingestion in the reduction of risk of inflammation. The combined analysis of the urine metabolome and clinical markers represents a promising approach in monitoring the metabolic impact of blueberries in persons with metabolic syndrome.

Improving Weight Loss by Combination of Two Temporary Antiobesity Treatments.

BACKGROUND: It is generally accepted that the efficacy with an intragastric balloon decreases after the first 4 months of treatment. Aim of this study is to evaluate if the association of a very low-calorie ketogenic diet (VLCKD) can improve the results in terms of weight loss parameters and co-morbidities, as compared to usually prescribed low-calorie diet (LCD). METHODS: For the present study (January 2016-June 2017), 80 patients (20 M/60 F, mean age 37.8 ± 6.1 years; excess weight 56 ± 10 kg; mean BMI 37.2 ± 3.8 kg/m2) underwent Orbera positioning. After 4 months, they were randomized into two groups according to the type of treatment: group A (Bioenterics intragastric balloon - Orbera + VLCKD) (n = 40), and group B (Orbera + LCD) (n = 40). RESULTS: All patients completed the study with good adherence to diet therapy treatment allocation. After the 6-month treatment period, at time of Orbera removal, mean weight loss was 19 kg and 12 kg in groups A and B respectively (p < 0.05). Mean BMI was 28.9 ± 2.8 and 31.6 ± 3.1 kg/m2 (p < 0.05), and %EWL was 33.1 ± 3.3 and 21.1 ± 2.9 (p < 0.05) in groups A and B respectively. During the last 2 months in group A, the mean weight loss was 8 kg, while in Group B, the main weight loss was 3 kg (p < 0.001). The VLCKD treatment induced a more significant reduction of major comorbidities related to metabolic syndrome. CONCLUSIONS: This study clearly indicates the efficacy of the prescription of very low-calorie ketogenic diet improving the efficacy of intragastric balloon positioning.

Lack of correlation between gastroesophageal reflux disease symptoms and esophageal lesions after sleeve gastrectomy.

BACKGROUND: The postoperative development or worsening of gastroesophageal reflux disease (GERD) represents the major drawback of laparoscopic sleeve gastrectomy (SG). A GERD diagnosis is often based only on symptoms and proton pump inhibitors (PPI) intake, while objective tests like esophagogastroduodenoscopy and pH measurements are performed less frequently. OBJECTIVES: To evaluate the association between reflux symptoms and GERD-related esophageal lesions. SETTINGS: University hospital, Rome, Italy. METHODS: A comprehensive clinical control entailing GERD symptoms, PPI intake, and esophagogastroduodenoscopy was proposed to all patients who underwent SG between June 2007 and February 2011, irrespective of the presence of GERD symptoms. One hundred forty-four of 219 patients agreed to take part in the study (follow-up rate: 65.8%). RESULTS: After a mean follow-up of 66 months, GERD symptoms and PPI intake were recorded in 70.2% and 63.9% of patients, respectively. Mean visual analogue scale score was 2.9 ± 3.3. The overall frequency of erosive esophagitis was 59.8%, while nondysplastic Barrett's esophagus was detected in 13.1%. The frequency of esophageal biliary reflux was 68%. GERD symptoms and visual analogue scale score were not significantly associated with the development of erosive esophagitis and Barrett's esophagus and the severity of the esophageal lesions. Moreover, the frequency of erosive esophagitis and Barrett's esophagus in patients consuming PPI were similar to that of patients without PPI. CONCLUSION: Symptoms investigation alone is not a reliable tool to diagnose GERD after SG. The use of objective diagnostic tests, such as esophagogastroduodenoscopy, should be carefully considered in the postoperative follow-up schedule of SG patients.

Adherence to Mediterranean Diet and Non-Alcoholic Fatty Liver Disease: Effect on Insulin Resistance.

OBJECTIVES: The prevalence of cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD), is increasing in western countries, because of changes in lifestyle and dietary habits. Mediterranean Diet (Med-Diet) is effective for cardiovascular prevention, but its relationship with NAFLD has been scarcely investigated. METHODS: We included 584 consecutive outpatients presenting with one or more cardiovascular risk factor such as type 2 diabetes mellitus (T2DM), arterial hypertension, overweight/obesity, and dyslipidemia. Liver steatosis was assessed using ultrasonography. Med-Diet adherence was investigated by a validated semiquantitative nine-item dietary questionnaire; patients were divided into low, intermediate, and high adherence. Insulin resistance was defined by the 75th percentile of homeostasis model of insulin resistance (HOMA-IR; ≥3.8). RESULTS: The mean age was 56.2±12.4 years and 38.2% were women. Liver steatosis was present in 82.7%, and its prevalence decreased from low to high adherence group (96.5% vs. 71.4%, P<0.001). In a multiple logistic regression analysis, hypertriglyceridemia (odds ratio (OR): 2.913; P=0.002), log (ALT) (OR: 6.186; P<0.001), Med-Diet adherence (intermediate vs. low OR: 0.115; P=0.041, high vs. low OR: 0.093; P=0.030), T2DM (OR: 3.940; P=0.003), and high waist circumference (OR: 3.012; P<0.001) were associated with NAFLD. Among single foods, low meat intake (OR: 0.178; P<0.001) was inversely significantly associated with NAFLD. In 334 non-diabetic NAFLD patients, age (OR: 1.035, P=0.025), high waist circumference (OR: 7.855, P<0.001), hypertriglyceridemia (OR: 2.152, P=0.011), and Log (ALT) (OR: 2.549, P=0.002) were directly associated with HOMA-IR, whereas Med-Diet score was inversely associated (OR: 0.801, P=0.018). CONCLUSIONS: We found an inverse relationship between Med-Diet and NAFLD prevalence. Among NAFLD patients, good adherence to Med-Diet was associated with lower insulin resistance. Our findings suggest that Med-Diet may be a beneficial nutritional approach in NAFLD patients.

Rhinocerebral zygomycosis with pansinusitis in a 14-year-old girl with type 1 diabetes: a case report and review of the literature.

BACKGROUND: Zygomycosis is a rare life-threatening fungal infection affecting mostly patients with predisposing conditions such as diabetes mellitus, immunodeficiency, haemochromatosis or major trauma. METHODS: We describe a case of rhinocerebral zygomycosis in a girl with type 1 diabetes and review previous published cases and treatment options. RESULTS: A 14-year-old girl with type 1 diabetes mellitus occurred with dental pain, facial swelling, ecchymosis and left eye decreased visual acuity, unresponsive to antibiotic therapy. The cultures of the sinusal mucosa were positive for fungal species belonging to the Zygomycetes. She performed antifungal therapy with posaconazole (POS) with a very slow improvement and a poor glycemic control, leading to blindness of the left eye. CONCLUSION: Our report adds further awareness on rhinocerebral zygomycosis and emphasizes on urgent diagnosis and timely management of this potentially fatal fungal infection through an adequate treatment.