
Mechanism of Fatty Acid-Induced Impairment of Glucose-Stimulated Insulin Secretion
Insulin Resistance Syndrome XPancreatic Beta Cell FunctionA prolonged elevation of plasma free fatty acids (FFA) impairs glucose stimulated insulin secretion. The concept of fatty acid impairment of glucose stimulated insulin secretion (lipotoxicity) has now been well accepted. Increased free fatty acid flux from adipose tissue to non-adipose tissue, resulting from abnormalities of fat metabolism, participates in and amplifies many of the metabolic derangements that are characteristic of insulin resistance syndrome and type 2 diabetes. Lipotoxicity is also likely to play an important role in the progression from normal glucose tolerance to fasting hyperglycemia and conversion to frank type 2 diabetes in insulin resistant individuals. This area of research is now focused on determining the mechanisms whereby FFAs impair b-cell function. There is some evidence to suggest that lipotoxicity could be mediated through induction of reactive oxygen species (ROS). N-acetylcysteine (NAC) is a known potent antioxidant and has been used experimentally in a number of medical conditions in humans for its protective antioxidant effects. The investigators now plan to administer NAC orally to humans for 48 hours to examine the effects of antioxidant therapy in ameliorating the deleterious effects of FFAs on pancreatic beta cell function. NAC is currently approved for the treatment of acetaminophen overdose and is also used as a mucolytic agent. The investigators are now using NAC as an antioxidant to determine whether it protects the pancreatic beta cell against the toxic effects of FFAs, as outlined in the detailed study protocol. This is a proof-of-principle study and is not designed to develop n-acetylcysteine for therapeutic use.

MARIS Study; Mediterranean Approach to Reduce Insulin-Resistance Study
Insulin ResistanceMetabolic Syndrome X3 moreBackground: During the 1990s, the prevalence of the metabolic syndrome in the Netherlands ranged from 3% in women of 20-39 yrs to at least 33% in men 55 yrs and older and it is expected to increasing. Prevention is therefore warranted. In this respect the amount and type of fat in the diet deserves attention. Recently, an intervention study reported that a diet high in mono-unsaturated fatty acids (MUFA) such as from olive oil, increased insulin sensitivity in healthy subjects. However, additional beneficial effects can be expected from the Mediterranean diet as a whole. Hypothesis: Replacing saturated fatty acids (SFA) by mono-unsaturated fatty acids (MUFA) will improve hyperinsulinemia and dyslipidemia, and a typical Mediterranean diet will even have more pronounced effects. Study objectives: To investigate the impact of the Mediterranean diet, and especially the intake of MUFA, on markers of the metabolic syndrome in high-risk subjects. Methods: The controlled dietary intervention will include 60 subjects aged 40-65 years with moderate abdominal obesity. After a run-in diet for 2 weeks they will be assigned randomly to receive one of the three diets for a period of 8 weeks. Measurements of serum insulin concentration and other parameters will be carried out at weeks 2 and 10. Expected results: Our study will provide information on the role of MUFA and the expected beneficial impact of other factors of the Mediterranean type of diet on the metabolic syndrome.

Underlying Abnormalities in Fat and Muscle Leading to Lipodystrophy Syndrome
HIV InfectionsLipodystrophy1 moreWith the advent of highly active anti-retroviral therapy(HAART), patients with HIV disease are developing a series of metabolic abnormalities including peripheral fat wasting, increase in truncal fat, high serum triglyceride levels, insulin(a hormone that controls blood sugar) resistance with an increased incidence of Type 2 Diabetes Mellitus and elevated blood pressure. The premise of this study is that abnormalities in the ability of fat and muscle tissue to respond to the hormone insulin may be the cause of the diabetes mellitus, high serum triglyceride levels and abnormal fat distribution. The purpose of the study is to assess how insulin resistant patients with HIV disease are and if their fat and muscle tissue are responding abnormally to insulin. This is done by administering insulin and taking small tissue samples of fat and muscle from the upper thigh and assessing how good insulin acts in these tissues. Patients with HIV disease will be admitted into the study after undergoing a screening medical history and examination. Once patients qualify, they will have their insulin resistance measured as well as the response of their fat and muscle to insulin; blood levels of glucose (sugar), cholesterol and triglycerides will be measured; body fat will be assessed using radiological tests; a detailed medical history will be obtained to assess risk factors for developing this syndrome. Patients who are found to be insulin resistant will be offered a trial of an insulin sensitizing agent, called Avandia, for 6-12 weeks. It is hoped that the Avandia will restore the body's ability to respond normally to insulin (as it does in patients with Diabetes) and perhaps improve the fat abnormalities as well. All the same measures will be performed at the end of the course of Avandia as were done at baseline. Patients who are not insulin resistant will be asked to come back yearly to assess whether they develop insulin resistance over time. This study will continue to recruit patients over the next 3 years.

Diet and Metabolic Inflammation
Insulin ResistanceDiabetes3 moreObesity is a risk factor for several common cancers, including those of the breast, colon, liver, and pancreas. Proposed molecular links between obesity and these types of cancer include systemic inflammation, hyperinsulinemia, and changes in the serum concentrations of sex steroid hormones and adipokines. All of these are strongly linked to low-grade chronic inflammatory processes in expanded adipose tissue. The objective of this proposal is to test the hypothesis that adipose tissue inflammation can be reduced by the foods we eat.

Evaluation of the Impact of a Nutritional Supplement Made of Vegetable Oils in People at Risk of...
Insulin ResistanceMetabolic and cardiovascular diseases are the first cause of morbidity and mortality throughout the world, including Latin America and Colombia. Asymptomatic elevations of blood glucose, insufficient response to normal insulin concentrations (called insulin resistance), overweight and obesity can cause severe damage to body organs, leading to complications and even death. Worryingly, the prevalence of prediabetes is on the rise and efforts in public health policies made to contain this epidemic have had a very limited impact. This has prompted an intense search for non-pharmacological interventions. One of the most promising areas is research on "nutraceuticals", foods capable of positively impacting risk factors. However, there are insufficient nutritional or supplementary alternatives to favorably impact carbohydrate metabolism and cardiovascular risk factors in individuals at risk of diabetes. This project will evaluate the effects of the administration of a dietary supplement composed of vegetable oils. The fat composition of these oils is likely to impact positively on the metabolic profile of subjects at risk of diabetes and cardiovascular conditions.

Vitamin D Supplementation and and Glycemic Indexes
DeficiencyVitamin D1 moreAge affect insulin sensitivity and the metabolism, and vitamin D status was shown to have a correlation with markers of insulin resistance. That's why, we aimed in our trial to study the effect of vitamin D supplementation on glycemic markers and index of insulin resistance.

Dietary Approaches for Cardiometabolic Health
ObesityAbdominal4 moreThis pilot study aims to recruit 30 adults with abdominal obesity, without major chronic disease, and test whether clinical dietary advice that is solely focused on the timing of eating (time restricted eating), has an effect on cardiometabolic health compared to standard dietary advice for cardiometabolic health, which is focused on content. The goal of this pilot study is to develop and hone dietary counseling approaches for time restricted eating for RD's in a clinical practice paradigm, and collect data on testing this intervention compared to standard dietary counseling approaches for cardiometabolic health.

Acute and Chronic Metabolic Flexibility in Individuals Living With Obesity: The i-FLEX Study
ObesityObesity; Endocrine2 moreRegular exercise is a cornerstone in the prevention and the management of cardio-metabolic risk factors. Some of the beneficial effect of exercise training occurs through metabolic flexibility' enhancement. Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand, and previous literature has shown that individuals living with obesity have an impaired metabolic flexibility compared to lean individuals. However, there is a lack of empirical evidence on the impact of sprint interval training on metabolic flexibility and whether this translates into clinically meaningful outcomes. This study will evaluate the impact of 4-week sprint interval training in normal weight individuals as well as individuals living with obesity on acute and chronic metabolic flexibility, irisin secretion and insulin sensitivity.

Effect of Low-carbohydrate/High-fat Diet on Glucose Tolerance and Lipid Profile in Lean, Healthy...
Insulin SensitivityWeightIntervention studying the effect of a low-carbohydrate/high-fat (LCHF) diet as well as on bout of exercise in combination with either a normal diet or a LCHF diet, in relation to glucose metabolism, insulin sensitivity, lipid profile and body composition.

Cardiovascular Effects of Metformin on Obesity
Insulin ResistanceIt has been shown that asymptomatic obese adolescents can demonstrate abnormal regional myocardial contraction, with preserved global cardiac function. Metformin has been shown to decrease cardiovascular mortality in patients with type 2 diabetes and insulin resistance, but the mechanism of cardiovascular protection is unknown. The purpose of this study is to evaluate the reversibility of subclinical cardiovascular abnormalities in obese adolescents with insulin resistance after a six-month course of Metformin. The investigators hypothesized that the beneficial effects of Metformin will be progressive and sustained after six months of therapy.