Ram Weiss

Ram Weiss
Hebrew University of Jerusalem | HUJI · Braun School of Public Health and Community Medicine

MD PhD

About

117
Publications
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Introduction

Publications

Publications (117)
Article
OBJECTIVE The carbohydrate-insulin model (CIM) claims that chronic exposure to hyperinsulinemia induced by dietary carbohydrates explains development of obesity via direct effects of insulin and/or low postprandial metabolic fuel levels. We aimed at testing whether indices of hyperinsulinemia and postprandial glucose levels can predict increases in...
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Background and objective Childhood obesity is associated with later development of significant renal morbidity. We evaluated the impact of the degree of insulin sensitivity on estimated glomerular filtration rate (eGFR) and determined the factors associated with eGFR in obese children. We further tested the relation of eGFR to clinical outcomes suc...
Article
Background: Severe obesity among adolescent shows a worrisome trend in regard of its increasing prevalence and poses a great challenge for treatment. Conservative measures have modest effects on weight loss, usually fail in achieving a sustainable weight loss and resolution of comorbidities. This has led to greater utilization of bariatric surgery...
Article
Childhood obesity is one of the most serious global public-health challenges of the twenty-first century. Over the past four decades, the number of children and adolescents with obesity has risen more than tenfold. Worldwide, an increasing number of youth are facing greater exposure to obesity throughout their lives, and this increase will contribu...
Article
We examined the relationship between insulin clearance, insulin sensitivity, and β-cell function and the longitudinal effect of insulin clearance on β-cell function in lean and obese insulin-sensitive and insulin-resistant adolescents. A hyperinsulinemic-euglycemic and a hyperglycemic clamp were performed in 110 youths to quantify hepatic and perip...
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Aims In this study, we investigated whether adipose tissue insulin resistance (IR) is affected by the degree of obesity during the fasting and post-prandial state, independent of glucose tolerance among obese children and adolescents. We also tested whether systemic subclinical inflammation is associated with adipose tissue IR. Methods Subjects we...
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Background: Type 2 diabetes is preceded by a prediabetic stage of impaired glucose tolerance that affects 10-23% of youth and is expected to double over the next decade. The natural history of impaired glucose tolerance and the determinants of β-cell dynamic response have never been investigated longitudinally in young people. We aimed to investig...
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Objective: To compare cardiovascular risk factor clustering (CVRFC) in severely obese youth with those with lower degrees of obesity. Study design: We divided a childhood obesity clinic derived cohort into the degrees of obesity (class I, II, and III) and added a "class IV" category corresponding to >160% of the 95th centile of body mass index (...
Chapter
Obesity during childhood is a key driver of the development of insulin resistance. This is mainly due to two mechanisms—lipid partitioning patterns favoring greater deposition of fat in the intra-abdominal compartment and within insulin-responsive tissues (such as the skeletal muscle and liver) and fat tissue-derived cytokine secretion which affect...
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Urban-dwelling Palestinians have been shown to have higher cardiovascular morbidity and mortality and prevalence of diabetes than urban Israelis. Inflammation is implicated in the etiology of these conditions. We hypothesized that increased inflammatory activation, manifested as increased GlycA, a novel biomarker of global inflammation, would be ev...
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Context Homeostatic energy balance is controlled via the hypothalamus, whereas regions controlling reward and cognitive decision-making are critical for hedonic eating. Eating varies across the menstrual cycle peaking at the midluteal phase. Objective To test responses of females with regular cycles during midfollicular and midluteal phase and of...
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Obesity has been estimated to decrease life expectancy by as little as 0·8 years to as much as 7 years, and is the second leading cause of preventable death—after smoking—in the USA. Alongside the increase in the prevalence of obesity, prediabetes and type 2 diabetes have become more common in adolescents. Yet, little is known about the pathogenesi...
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Context: Adipocytes represent an important insulin responsive tissue taking an active part in glucose metabolism. Objective: To assess adipose tissue insulin resistance across the spectrum of glucose tolerance and to test its relation with free fatty acid (FFA) suppression during an oral glucose tolerance test (OGTT) Design: Cross sectional anal...
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Childhood obesity is one of the greatest health challenges of the 21st century. The EASO COTF is convinced that classifying obesity as a chronic disease in children and adolescents is a crucial step for increasing individual and societal awareness, and for improving early diagnosis and intervention. Such a classification will enhance the developmen...
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ASPIRE In-Home randomized 247 subjects with type 1 diabetes to sensor-augmented pump therapy with or without the Threshold Suspend (TS) feature, which interrupts insulin delivery at a preset sensor glucose value. We studied the effects of TS on nocturnal hypoglycemia (NH) in relation to baseline hemoglobin A1c (A1C) and change in A1C during the stu...
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Hypoglycemia varies between patients with type 1 diabetes and is the main obstacle to therapy intensification. We investigated known and potential risk factors for hypoglycemia in subjects with type 1 diabetes. In the ASPIRE In-Home study (NCT01497938), a randomized trial of the threshold suspend (TS) feature of sensor-augmented insulin pump (SAP)...
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Nutritional deficiencies are common among morbidly obese patients. Data are scarce for patients who have undergone laparoscopic sleeve gastrectomy (LSG). The aim of the study is to clarify the prevalence of deficiencies and to identify risk factors for postoperative deficiencies. Hebrew University, Israel. Preoperative and 1-year postoperative data...
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To evaluate differences in the triglyceride to HDL-cholesterol ratio (TG/HDL), thought to be a proxy measure of insulin resistance, between Palestinian and Israeli adults in view of the greater incidence of coronary heart disease and high prevalence of diabetes in Palestinian Arabs. A population-based observational prevalence study of cardiovascula...
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Impaired glucose effectiveness (GE) plays a role in the deterioration of glucose metabolism. Our aim was to validate a surrogate of GE derived from an oral glucose tolerance test (OGTT), and to assess the impact of degrees of obesity and of glucose tolerance on it. The OGTT-derived surrogate of GE (oGE) was validated in obese adolescents who underw...
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Nonalcoholic fatty liver disease (NAFLD) is commonly found in adults and adolescents with type 2 diabetes (T2DM). The cause-effect relations of these 2 conditions are complex and it is difficult to decipher whether one drives the other or vice versa. Genetic predispositions, along with obesity, are probably shared culprits of both. NAFLD may preced...
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Aims/hypothesis With the increase in gestational diabetes mellitus (GDM), there is a growing need to understand the effects of intrauterine glucose exposure on the newborn at birth and later in life. The risk of developing impaired glucose tolerance (IGT) in individuals exposed to diabetes in utero has not been adequately investigated. Methods W...
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The purpose of this study was to compare the effects of two bariatric procedures on abdominal lipid partitioning and metabolic response. Fifty-one patients (RYGB 31(11 M/20 F); (SG) 20(8 M/12 F)) who met the criteria of metabolic syndrome before the operation were followed following Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Viscer...
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Some obese individuals have no cardiometabolic abnormalities; they are 'metabolically healthy, but obese' (MHO). Similarly, some non-obese individuals have cardiometabolic abnormalities, that is, 'metabolically at risk, normal weight' (MANW). Previous studies have suggested that early-onset obesity may be associated with MHO. We aimed to assess whe...
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Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB), has a rapid and drastic effect in obese patients with type 2 diabetes (T2D), many of whom show complete remission of the disease within days of the procedure. This has introduced the option of a surgical mode of diabetes therapy (1–3). The exact mechanisms by which RYGB drives clinica...
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Aims/hypothesis: Bariatric surgery is gaining acceptance as a 'metabolic surgical intervention' for patients with type 2 diabetes. The optimal form of surgery and the mechanism of action of these procedures are much debated. We compared two bariatric procedures for obese patients with type 2 diabetes and evaluated their effects on HbA1c and glucos...
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Metabolic syndrome comprises a cluster of cardiovascular risk factors (hypertension, altered glucose metabolism, dyslipidemia, and abdominal obesity) that occur in obese children. However, metabolic syndrome can also occur in lean individuals, suggesting that obesity is a marker for the syndrome, not a cause. Metabolic syndrome is difficult to defi...
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Paralleling the worldwide epidemic in childhood obesity, in the last decade we have observed a rise in the prevalence of metabolic syndrome (MetS) in pediatrics. The MetS comprises a cluster of cardiovascular risk factors. Multiple definitions have been proposed for the syndrome in the pediatric age group, but they are very difficult to test and va...
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Hypothalamic obesity is an intractable form of obesity syndrome that was initially described in patients with hypothalamic tumours and surgical damage. However, this definition is now expanded to include obesity developing after a variety of insults, including intracranial infections, infiltrations, trauma, vascular problems and hydrocephalus, in a...
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We sought to determine whether obese adolescents with high-"normal" 2-h post-oral glucose tolerance test glucose levels display defects in insulin secretion and sensitivity associated with future development of impaired glucose tolerance (IGT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and insulin secretion by applying m...
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Screening for acanthosis nigricans (AcN) in overweight children is repeatedly recommended. The significance of AcN, and its relation to central obesity in children, is unclear. To compare clinical and anthropometric parameters associated with adiposity, between overweight and obese children with and without AcN. One hundred and forty-nine overweigh...
Article
Liver steatosis, known as non-alcoholic fatty liver disease (NAFLD) is common among obese children. Deposition of lipid within the liver represents part of an abnormal lipid partitioning pattern, most commonly associated with increased intra-abdominal fat. Lipid deposition in the liver can be a cause of peripheral insulin resistance via local accel...
Article
We evaluated whether the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio is associated with insulin resistance (IR) in a large multiethnic cohort of obese youths. Obese youths (1,452) had an oral glucose tolerance test and a fasting lipid profile. Insulin sensitivity was estimated using the whole body insulin sensitivity index (WBISI) and homeosta...
Article
Bariatric surgery is gaining acceptance as an effective and well tolerated treatment of morbid obesity in adults yet experience in obese children is still lacking. The purpose of this review is to highlight recent findings in this exciting field and identify the knowledge gaps. One randomized controlled trial and several case series have been publi...
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To assess whether the fasting triglyceride-to-high-density lipoprotein (HDL)-cholesterol (TG/HDL) ratio in adolescence is predictive of a proatherogenic lipid profile in adulthood. A longitudinal follow-up of 770 Israeli adolescents 16 to 17 years of age who participated in the Jerusalem Lipid Research Clinic study and were reevaluated 13 years lat...
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The aim of this analysis was to evaluate glucagon and c-peptide concentrations in two scenarios: euglycemic hyperinsulinemia and hyperglycemic hyperinsulinemia. We postulated that worsening obesity and insulin resistance will be reflected as an up-regulated (less suppressible) islet secretion profile. Eighty-two [34 obese with normal glucose tolera...
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Many bariatric operations are associated with reduced food tolerance and frequent vomiting, which may cause nutritional deficiencies and influence quality of life. However, the impact of different bariatric procedures on quality of eating and food tolerance has not yet been studied enough. Two hundred and eighteen participants filled a quality of e...
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Recently, the deleterious metabolic effects of visceral fat [visceral adipose tissue (VAT)] deposition were challenged, and liver fat emerged as having a key independent role in the modulation of cardiometabolic risk factors. We explored the relation between liver fat content and VAT in 3 ethnic groups and evaluated whether the ethnic differences i...
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We evaluated the role of fatty liver in the alteration of insulin sensitivity and beta-cell function in two groups of obese adolescents, differing in hepatic fat content (hepatic fat fraction [HFF]) but with similar intrabdominal intramyocellular lipid content (IMCL) and overall degree of obesity. We studied 23 obese adolescents with high HFF (HFF...
Chapter
Obesity in children and adults is associated with resistance to the metabolic effects of insulin. The term “insulin resistance” is commonly used to describe the resistance of skeletal muscle and liver to insulin-dependent glucose metabolism: insulin resistance reduces myocellular glucose uptake and utilization, increases hepatic glucose production,...
Article
The metabolic syndrome defines the clustering of cardiovascular risk factors and is a driven by peripheral insulin resistance. The 'driving force' of the syndrome, i.e. insulin resistance, develops mainly in obese children due to a specific pattern of lipid partitioning characterized by increased deposition of fat in the visceral compartment as wel...
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The prevalence of obesity among children and adolescents is on the rise. The majority of overweight or obese children are treated by primary health care providers including paediatricians, family practitioners, dieticians, nurses, and school health services - and not by specialists. The majority of obese children have no underlying medical disorder...
Article
Along with the rise in the prevalence of obesity in childhood, a growing number of children and adolescents require treatment for severe obesity. The success rate of behavioral and pharmacological interventions to achieve sustainable weight loss and recovery from accompanying comorbidities in children with obesity (defined as BMI >95th percentile f...
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These are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, Summerbell CD. Interventions for treating obesity in children. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001872. DOI: 10.1002/14651858.CD001872.pub2. Fur...
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Participation of adolescents and young women in strenuous sports activity may lead to various metabolic and psychological derangements of clinical relevance to the endocrinologist. The most common manifestations encountered in practice are primary and secondary amenorrhea, reduced bone mineral density and eating disorders. The occurrence of all thr...
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To assess the prevalence of nutritional deficiencies amongst people who suffer from morbid obesity and are candidates for bariatric surgery and to evaluate the relations between pre-operative nutritional deficiencies and demographic data and co-morbidities. Preoperative blood tests of 114 patients (83 women and 31 men) were collected. The blood tes...
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Bariatric surgery is gaining acceptance as an efficient treatment modality for obese patients. Mechanistic explanations regarding the effects of bariatric surgery on body composition and fat distribution are still limited. Intra-abdominal and subcutaneous fat depots were evaluated using computed tomography in 27 obese patients prior to and 6 months...
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Pharmaceutical companies decide how much to invest in developing new drugs and promoting existing ones, thereby influencing the rate of drug discovery and the state of biomedical research funding¹. The relative emphasis on innovation compared with marketing depends on how these activities affect the short-term profitability and the long-term value...
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Adiponectin has been postulated to affect lipid and insulin signal transduction pathways. We evaluated the relationships of plasma adiponectin with lipoprotein mean particle size and subclass concentrations, independent of obesity and insulin sensitivity. A cross-sectional analysis of 884 young Israeli adults who participated in the population-base...
Article
Reducing postprandial hyperglycemia and hypoglycemia is a major challenge in the treatment of patients with diabetes. Studies suggest that heating the insulin injection site may accelerate insulin absorption. InsuPatch (InsuLine Medical Ltd., Petach-Tikva, Israel) is a device intended to accelerate subcutaneous insulin delivery using an insulin pum...
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Cross-sectional studies showed worsening of cardiovascular risk factors with increasing severity of childhood obesity. The aim of this study was to investigate the impact of obesity dynamics on cardiovascular risk factors and on the stability of the diagnosis of metabolic syndrome (MS) in obese youth. A longitudinal assessment of components of the...
Article
The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth. We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulat...
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The rise in the prevalence of obesity in the last few decades and its growing impact on health has driven the scientific community to investigate the physiological basis of energy homeostasis and mechanisms of satiety, and seek targets for intervention against this burgeoning epidemic. Recent findings highlight the role of gut-derived, hormonal sig...
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To evaluate the accumulation pattern of intramyocellular lipids (IMCLs) in striated muscle during the development and progression of diabetes, using a novel scanning electron microscopic method. Hyperglycemia was induced by feeding diabetes-prone (DP) Psammomys obesus a high-energy (HE) diet. Lipid accumulation within gastrocnemius muscle fibers wa...
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The growing number of obese children and adolescents across the world creates a diagnostic challenge to caregivers. The early clinical manifestations of abnormalities related to childhood obesity, attributed to obesity-driven insulin resistance, are impaired glucose metabolism and nonalcoholic fatty liver disease. Both have no symptoms and demand a...
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The fields of obesity, diabetes, and hypertension are gaining major attention in the last 2 decades, since the obesity epidemic is driving a parallel increase in related morbidity. Recent progress in the research of these inter-related conditions is bringing a tremendous expansion of basic and clinical data alongside a wealth of novel technologies...
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To explore whether an imbalance between the visceral and subcutaneous fat depots and a corresponding dysregulation of the adipokine milieu is associated with excessive accumulation of fat in the liver and muscle and ultimately with insulin resistance and the metabolic syndrome. We stratified our multi-ethnic cohort of 118 obese adolescents into ter...
Article
Obese youth are at significant risk for the development of altered glucose metabolism and other elements of the MS. The degree of obesity and the pattern of lipid partitioning are strongly related to the metabolic phenotype of the obese child. Lipid deposition in insulin-responsive tissues (such as liver and muscle) and secretion of cytokines from...
Article
Postnatal weight gain may predispose to the development of obesity during childhood. The aims of this study were to study the impact of weight gain during specific periods of the first year of life and of feeding patterns on the body mass index (BMI) of adolescents. Growth records during the first 24 months of life of 88 obese and 214 non-obese 12...
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The significant rise in the prevalence of obesity in children and adolescents over the past three decades has led to a rise in the incidence of severe insulin resistance and consequently of type 2 diabetes in this age group. Type 2 diabetes is caused by a combination of increased insulin resistance and decreased insulin secretion. Peripheral insuli...
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Ketoacidosis is a common condition in patients with new onset type 1 diabetes and remains a major reason for hospitalization of those with established disease. The major cause of mortality in ketoacidosis is cerebral edema. Although rarely diagnosed on a clinical basis, cerebral edema may have subtle manifestations and is probably under-diagnosed....
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Impaired glucose tolerance and impaired fasting glucose represent two potentially reversible prediabetes conditions. Previous reports from various regions across the globe indicate that both conditions may be relatively common in obese children and adolescents. The major factor driving the development of compromised glucose metabolism in obese yout...
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Obesity does not necessarily imply disease and similarly obese individuals may manifest obesity-related morbidity or seemingly be in reasonably good health. Recent studies have shown that patterns of lipid partitioning are a major determinant of the metabolic profile and not just obesity per se. The underlying mechanisms and clinical relevance of l...