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Purpose of Review: Drug-resistant epilepsy represents around one-quarter of epilepsies worldwide. Although ketogenic diets (KD) have been used for refractory epilepsy since 1921, the past 15 years have witnessed an explosion of KD use in the management of epilepsy. We aimed to review evidence from randomized controlled trials (RCTs) regarding the efficacy and safety of KD in drug-resistant epilepsy in children and adolescents. Recent Findings: A literature search was performed in the Pubmed, Cohrane, Scopus, ClinicalTrials.gov, and Google Scholar databases. Predefined criteria were implemented regarding data extraction and study quality. Data were extracted from 14 RCTs in 1114 children and adolescents aged from 6 months to 18 years. Primary outcome was seizure reduction after the intervention. In 6 out of the 14 studies, there was a statistical significant seizure reduction by > 50% in the KD-treated group compared with the control group over a follow-up of 3–4 months. Secondary outcomes were adverse events, seizure severity, quality of life, and behavior. Gastrointestinal symptoms were the most frequent adverse events. Serious adverse events were rare. Summary: We conclude that the KD is an effective treatment for drug-resistant epilepsy in children and adolescents. Accordingly, RCTs investigating long-term impact, cognitive and behavioral effects, and cost-effectiveness are much anticipated. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Purpose of Review: The COVID-19 pandemic has challenged public health to a significant extent by markedly increasing morbidity and mortality. Evidence suggests that obesity and hypovitaminosis D constitute important risk factors for SARS-CoV-2 infection, severity of disease, and poor outcomes. Due to their high prevalence globally, obesity and hypovitaminosis D are considered pandemics. This review presents current epidemiologic and genetic data linking obesity, hypovitaminosis D, and COVID-19, highlighting the importance of the convergence of three pandemics and their impact on public health. We also briefly summarize potential mechanisms that could explain these links. Recent Findings: Epidemiologic data have shown that obesity is an independent risk factor for COVID-19, severe disease and death, and genetic evidence has suggested a causal association between obesity-related traits and COVID-19 susceptibility and severity. Additionally, obesity is independently associated with hypovitaminosis D, which is highly prevalent in subjects with obesity. Hypovitaminosis D is independently associated with a higher risk for COVID-19, severity, hospitalization, infectious complications, acute respiratory distress syndrome, and poor outcomes. However, genome-wide association studies have not revealed any causal association between vitamin D levels and the risk for COVID-19, while there is no robust evidence for a beneficial role of vitamin D supplementation in the prevention and treatment of COVID-19. Summary: In the context of the ongoing COVID-19 pandemic, the epidemiologic impact of obesity and hypovitaminosis D is emphasized. Efforts to increase public awareness and reinforce preventive and therapeutic measures against obesity and hypovitaminosis D are strongly required. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Orthorexia nervosa (ON) is an unspecified feeding or eating disorder (USFED) characterized by an exaggerated, unhealthy obsession with healthy eating. Typical eating disorders (EDs) and USFEDs are common among patients with diabetes mellitus (DM), which complicates metabolic control and disease outcomes. The present systematic review summarizes the evidence on the prevalence of ON symptomatology among patients with DM. PubMed, Web of Science, Scopus, and grey literature were searched, and relevant observational studies were screened using the Rayyan software. The quality of the studies was assessed using the appraisal tool for cross-sectional studies (AXIS) and the Newcastle–Ottawa scale (NOS). Out of 4642 studies, 6 fulfilled the predefined criteria and were included in the qualitative synthesis. Most studies relied on the ORTO-15 or its adaptations to identify ON among patients with DM. No apparent sex or age differences exist regarding the prevalence of ON symptoms. None of the studies compared the prevalence of ON in patients with type 1 and type 2 DM. Most of the research was of average to good methodological quality. In conclusion, patients with DM often exhibit ON tendencies, although research is still limited regarding the etiology or mechanistic drivers behind ON and the characteristics of patients with a dual ON–DM diagnosis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Purpose of Review: Understanding the effects of dietary manipulations on intrahepatic triglyceride (IHTG) balance will have important implications for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). Recent Findings: Reducing calorie intake to induce weight loss is the most potent intervention to decrease IHTG. Carbohydrate restriction during the initial stages of weight loss may be particularly beneficial, but at later stages, the amount of weight loss predominates over diet composition. By contrast, during weight stability, restricting calories from fat seems to be optimal for depleting liver fat. The degree of dietary fat saturation and the glycemic index of the carbohydrate have inconsistent effects on IHTG. Recently, the matrix of some foods (e.g., dairy) has been inversely associated with NAFLD. Summary: Dietary macronutrients differ in their effects on liver fat depending on the energy balance and the matrix of the food in which they are consumed. Therefore, investigations into dietary approaches for managing NAFLD should shift their perspective from that of isolated nutrients to that of whole foods and diets and include useful mechanistic insights. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Purpose of Review: Evidence from observational studies suggests that obesity is associated with low vitamin D. As both obesity and hypovitaminosis D present an alarmingly increased prevalence worldwide, there is an intense research interest to clarify all aspects of this association. This review summarizes current evidence from meta-analyses investigating vitamin D status in obesity, including the effects of weight loss and bariatric surgery on vitamin D status and the outcomes of vitamin D supplementation on body weight. We also discuss potential pathophysiologic mechanisms and important controversies. Recent Findings: Data from meta-analyses consistently support an inverse association of vitamin D levels with body weight. However, the impact of weight loss on improving vitamin D status is small, while studies on the supplementation with vitamin D after bariatric surgery have shown conflicting results regarding vitamin D status. Moreover, interventional studies do not support a beneficial effect of vitamin D supplementation on body weight. These findings warrant a cautious interpretation due to important methodological limitations and confounding factors, such as high heterogeneity of studies, variable methods of determination of vitamin D and definition of deficiency/insufficiency, use of various adiposity measures and definitions of obesity, and inadequate adjustment for confounding variables influencing vitamin D levels. The underlying pathogenetic mechanisms associating low vitamin D in obesity include volumetric dilution, sequestration into adipose tissue, limited sunlight exposure, and decreased vitamin D synthesis in the adipose tissue and liver. Experimental studies have demonstrated that low vitamin D may be implicated in adipose tissue differentiation and growth leading to obesity either by regulation of gene expression or through modulation of parathyroid hormone, calcium, and leptin. Summary: Obesity is associated with low vitamin D status but weight loss has little effect on improving this; vitamin D supplementation is also not associated with weight loss. Evidence regarding vitamin D status after bariatric surgery is contradicting. The link between vitamin D and obesity remains controversial due to important limitations and confounding of studies. More research is needed to clarify the complex interplay between vitamin D and adiposity. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

The aims of the present study were to determine whether available "fasting" and oral glucose tolerance test-derived insulin sensitivity indices could effectively discriminate between individuals with higher than normal insulin sensitivity, and whether they would all provide similar information in clinical practice. Sprint runners (n = 8), endurance runners (n = 8) and sedentary controls (n = 7) received a 75-g oral glucose tolerance test. All participants were healthy lean males, aged 21-29 years. Besides glucose and insulin responses, a total of nine such indices were computed. Fasting as well as post-load glucose concentrations were similar in the three groups, while basal plasma insulin and the insulinaemic response to glucose were both higher in untrained individuals (at P < 0.05 and P < 0.02, respectively). There were no differences between endurance and sprint runners. The results for insulin sensitivity, however, were quite variable: three indices showed that both groups of athletes were more insulin-sensitive than controls; three indicated that this was the case for endurance runners only; one indicated that this was the case for sprint runners only; and two showed that sprint runners were more insulin-sensitive than either sedentary individuals or endurance runners (all differences were significant at P < 0.05). Controlling for total body weight or lean mass did not effectively resolve this disagreement. Apparently, the various insulin sensitivity indices examined provided different quantitative and qualitative information, despite insulin action being greater in both groups of athletes relative to controls, as reflected by their similar glucose tolerance with lower insulin concentrations. We suggest, therefore, that the use and interpretation of such indices among physically active individuals be made with caution. © 2005 Taylor & Francis.

During emergency situations in developing countries, young children have been identified as the most nutritionally vulnerable group. Comparatively less is known regarding nutritional risk of individuals in well-nourished societies hit by a major disaster. The aim of the present study, therefore, was to assess the nutritional status of Greek people who were left homeless after the Athens 1999 earthquake. A total of 225 volunteers from two camps were surveyed for dietary intake information and surrogate measures of nutritional status. Energy consumption and anthropometric indices of the children and adolescents revealed no sign of undernourishment. On the other hand, adults and the elderly consumed considerably less energy than that required for long-term preservation of health. Short-term energy and protein deficits, however, did not jeopardise their nutritional status as it might have expected, on the basis of high body mass indexes and normal haematological and biochemical profiles that were documented. In conclusion, the results of the present study indicate that nutritional risk in the acute phase after a major emergency in a previously well-nourished population is rather low. This is especially true for younger individuals, probably due to increased provision from the family and the community. Nevertheless, older persons may face increased risk as the situation is prolonged. © 2004 Taylor & Francis Ltd.

Insulin resistance in adipose tissue increases the release of free fatty acids into the circulation, which likely contributes to impaired insulin action in liver and skeletal muscle associated with obesity. However, reliable assessment of adipose tissue insulin resistance requires performing a hyperinsulinemic-euglycemic clamp procedure in conjunction with a fatty acid tracer infusion to determine insulin-mediated suppression of lipolytic rate. We developed a simpler method for evaluating adipose tissue insulin resistance in vivo, determined as the product of palmitate rate of appearance into the bloodstream and plasma insulin concentration during basal conditions. We validated our Adipose Tissue Insulin Resistance Index (ATIRI) by comparison with an assessment of adipose tissue insulin resistance determined by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with a palmitate tracer infusion in 47 obese nondiabetic subjects (body mass index: 40.1 ± 9.3 kg/m(2)). We found the ATIRI correlated closely with adipose tissue insulin resistance assessed during the clamp procedure (r =-0.854, P < 0.001). These results demonstrate that the ATIRI provides a reliable index of adipose tissue insulin resistance in obese subjects.

Background & Aims An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure. Methods We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4 + T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors. Results Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4 + T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes. Conclusions Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people.

Data from studies in animal models indicate that certain lipid metabolites, particularly diacylglycerol, ceramide, and acylcarnitine, disrupt insulin action. We evaluated the relationship between the presence of these metabolites in the liver (assessed by mass spectrometry) and hepatic insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp with stable isotope tracer infusion) in 16 obese adults (body mass index, 48 ± 9 kg/m 2 ). There was a negative correlation between insulin-mediated suppression of hepatic glucose production and intrahepatic diacylglycerol (r = −0.609; P = .012), but not with intrahepatic ceramide or acylcarnitine. These data indicate that intrahepatic diacylglycerol is an important mediator of hepatic insulin resistance in obese people with nonalcoholic fatty liver disease.

Increased adipose tissue lipolytic activity is considered an important factor in the pathogenesis of skeletal muscle insulin resistance associated with obesity.The objective of the study was to evaluate the relationship between the rate of release of free fatty acids (FFA) into plasma and skeletal muscle insulin sensitivity in human subjects.We determined the palmitate rate of appearance (Ra) per kilogram fat-free mass (an index of FFA availability to lean tissues) during basal conditions and during insulin infusion (to simulate postprandial insulin concentrations) and skeletal muscle insulin sensitivity, defined as the percent increase in the glucose rate of disappearance, in 110 nondiabetic women (body mass index 20.6-46.4 kg/m(2)) by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer methods.Basal (r(s) = -0.379, P0.001) and insulin-suppressed (r(s) = -0.631, P0.001) palmitate Ra correlated negatively with skeletal muscle insulin sensitivity. However, the strength of the correlation was greater for palmitate Ra during insulin infusion than palmitate Ra during basal conditions (P = 0.0007) when lipolytic rates and FFA availability were reduced to less than 20% of basal values. The relative suppression of palmitate Ra correlated directly with the relative stimulation of glucose rate of disappearance during insulin infusion (r(s) = 0.530, P0.001).These data suggest that the correlation between FFA kinetics and muscle glucose metabolism is due to multiorgan insulin resistance rather than a direct effect of FFA itself on skeletal muscle insulin action and challenge the view that increased adipose tissue lipolytic rate is an important cause of insulin resistance.

ObjectiveShort-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic–pituitary–peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified.MethodsIn this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5–38.0 kg/m2) were prescribed a hypocaloric diet (−500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months.ResultsMetreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (PP for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups.ConclusionsLeptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.

Purpose of review Intrahepatic fat content is increasingly being recognized as an integral part of metabolic dysfunction. This article reviews available methods for the assessment of hepatic steatosis. Recent findings Apart from liver biopsy, there are several noninvasive radiologic modalities for evaluating nonalcoholic fatty liver disease. Ultrasonography, computed tomography, and traditional MRI remain largely qualitative methods for detecting mild to severe degrees of steatosis rather than quantitative methods for measuring liver fat content, even though novel attempts to collect objective quantitative information have recently been developed. Still, their sensitivity at mild degrees of steatosis is poor. Undoubtedly, most methodological advances have occurred in the field of MRI and magnetic resonance spectroscopy, which currently enable the accurate quantification of intrahepatic fat even at normal or near normal levels. Xenon computed tomography was also recently shown to offer another objective tool for the quantitative assessment of steatosis, although more validation studies are required. Summary Several modalities can be used for measuring intrahepatic fat and assessing steatosis; the choice will ultimately depend on the intended use and available resources.