Lipid and Glycogen Metabolism in Patients With Impaired Glucose Tolerance and Calcium Sensing Receptor...
Type 2 Diabetes MellitusPrediabetes (Insulin Resistance4 moreBackground: Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure, in part due to diabetic cardiomyopathy. However, the association between intracellular lipid accumulation and (myocardial) functional impairment is likely more complex than originally imagined. Recent studies suggest that not fat per se, but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction. In addition skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus. Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning. Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing. Hypothesis: In addition to total ectopic lipid deposition in the myocardium, myocardial lipid composition, i.e. the relative abundance of saturated and unsaturated fatty acids, and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy. Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene / FHH. Aims: Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy Characterization of the metabolic interplay between the myocardium, skeletal muscle, liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation Methods: 1H/13C and 31P magnetic resonance spectroscopy and imaging for measurements of myocardial, skeletal and liver lipid and glycogen content, abdominal adipose tissue distribution and composition, ATP synthesis and myocardial functional parameters Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues (myocardium, skeletal muscle, liver, adipose tissue). Hyperinsulinemic-hyperglycemic glucose clamp (HHC) with enrichment of the infused glucose with the stable isotope [1-13C]glucose to trace the incorporation of circulating glucose into myocardial glycogen in healthy insulin sensitive volunteers, prediabetic insulin resistant volunteers with impaired glucose tolerance, healthy subjects, patients suffering from type 2 diabetes mellitus, patients suffering from type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor.
The Effects of Freshwater Clam Extract on Blood Sugar, and Lipid Profile in Prediabetes Patients...
PrediabetesMetabolic Diseases3 moreThe purpose of this study is to determine whether the freshwater clam extract and its combination is effective on the improvement of glucose and lipid metabolism, also evaluate its ability to postpone prediabetes patients to become diabetes.
Inter-day Reliability of the Oral Glucose Tolerance Test Using Indirect Calorimetry
Glucose IntoleranceThe main aim of this study is to determine the inter-day reliability, by using indirect calorimetry, of the post-prandial macronutrient oxidation and energy expenditure after consuming oral glucose load solution.
The Effect of Anakinra on Insulin Secretion
Glucose IntoleranceImpaired Insulin Secretion1 moreRationale: Once diabetes develops, β-cell function progressively deteriorates and therapeutic approaches that prevent of delay loss of β-cell function are needed in the treatment of type 2 diabetes mellitus. Recent findings suggest that interleukin-1 (IL-1) may be involved in the progressive β-cell dysfunction in type 2 diabetes mellitus. Objective: to determine whether blocking IL-1β by recombinant human IL-1ra (anakinra) improves beta-cell function in subjects with β-cell dysfunction.
Hepcidin and Glucose Metabolism
Iron Deficiency Anemia of PregnancyIron Metabolism Disorders2 moreGestational diabetes mellitus (GDM), defined as hyperglycemia with blood glucose values above normal but below those diagnostic of DM, and iron deficiency (ID) with or without anemia (IDA) are common during pregnancy. Both disease patterns are associated with an increased risk of complications during pregnancy and at delivery and may have a variety of negative effects on different aspects of child development. Thus, GDM and ID/IDA during pregnancy should be prevented. Whether iron supplementation with high oral doses acutely increases hepcidin during pregnancy, and whether this acute iron-induced increase in hepcidin decreases insulin sensitivity, is uncertain.
Effects of 3 Months of Supervised Exercise Training
Overweight/ObesityGlucose Intolerance2 moreThe incidence of type 2 diabetes is increasing worldwide. Because of cardiovascular morbidity and mortality associated with type 2 diabetes, it is imperative to propose methods of prevention and this in early stage of abnormal glucose metabolism. This study will assess the beneficial effects of physical activity (acute and chronic effects) (the subjects being their own controls) on cardiometabolic and inflammatory biomarkers in 3 conditions : unstimulated (fasting and resting conditions) and stimulated conditions: postprandial response to a standardized meal preceded or not by an exercise bout. The investigators hypothesized that an acute bout of exercise will decrease the postprandial inflammatory response to a standardized meal and that this effect of exercise will be increased after 3 months of exercise training.
Metabolic and Genetic Impacts of Energy Drinks in Youth
NutritionPediatric Obesity6 moreCaffeine containing energy drinks (CCED) are beverages that typically contain mixtures of simple sugars, caffeine and may contain vitamin, mineral and/or herbal preparations. In Canada, the consumption of CCEDs among adolescents is a regular occurrence and a common part of the everyday diet. Contributing to the obesity epidemic in youth is the consumption of energy drinks; yet no data on the metabolic responses to CCEDs exists. This study will examine the metabolic implications of CCED consumption in adolescents, aged 13-19 years. The investigators hypothesize that CCEDs will impair glucose tolerance by ~30% in lean adolescents and the primary cause of the insulin resistance will be caffeine. Obese individuals will experience a similar level of glucose impairment, but a greater rise in blood glucose compared to their lean counterparts (i.e. higher starting glucose level). For many, this additional, caffeine-induced rise will expose them to hyperglycemia, putting some individuals in the glucose intolerant or transient diabetic range. It is hypothesized that continued metabolic insult resulting from CCEDs may predispose susceptible individuals to chronic metabolic diseases later in life. The investigators will also examine the genetic basis of caffeine-induced glucose intolerance. This gene-diet interaction could explain why caffeine may be much more metabolically harmful for some individuals compared to others. The study of 'metabolomics' will also be utilized to analyze caffeine and caffeine metabolites such as theobromine, theophylline, and xanthine. This will be accomplished using Nuclear Magnetic Resonance (NMR) spectroscopy. Results from this study will have the potential to alter current perceptions that CCED are 'harmless' and will have far reaching implications for both medical professionals and legislators alike.
Women With Minor Degrees of Glucose Intolerance and the Postpartum Glucose Tolerance Test
Glucose Tolerance Impaired in PregnancyThe aim of this study is to offer a 75g postpartum glucose tolerance test to women with minor degrees of glucose intolerance and to assess if these women are significantly different from women who were diagnosed as GDM (Gestational Diabetes Mellitus)
Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous...
Cystic Fibrosis Homozygous for Phe 508 Del CFTRGlucose Intolerance or Newly Diagnosis DiabetesCystic Fibrosis related diabetes (CFRD), a major factor of morbid-mortality in CF, is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. At the physiopathology level, insulin secretion is determinant in the glucose tolerance abnormalities in CF. Indeed insulin secretion is dependent of the CFTR activity at the beta cell surface and inhibition of CFTR leads to a decrease in insulin secretion. Recently, the combination of the lumacaftor, a CFTR corrector, with Ivacaftor, a CFTR potentiator, was studied in patient with CF homozygous for the Phe508 del CFTR mutation patients and showed an improvement of the respiratory state in comparison with the placebo group. These data suggests that lumacaftor in combination with ivacaftor in targeting CFTR action may have an early impact on the insulin-secretion and consequently on the glucose tolerance.
Study to Investigate the Pathophysiology of Type 2 Diabetes in Youth
Impaired Glucose TolerancePre-diabetes3 moreThe purpose of the study is to determine the role of beta-cell function and insulin resistance in the development of impaired glucose tolerance (IGT) and type 2 diabetes in children and adolescents who have an increased risk of developing type 2 diabetes due to overweight/obesity or a family history of overweight/obesity, diabetes and/or impaired fasting glucose. It is hypothesized that: 1)Obese adolescents with IGT will be more insulin resistant than obese adolescents with NGT. Insulin resistance will be the best predictor of changes in glucose tolerance status., 2)Beta cell function will be impaired in obese adolescents with IGT compared to obese adolescents with NGT., 3)Obese adolescents with IGT will present with greater intramyocellular, intrahepatic and visceral fat than obese adolescents with NGT. Furthermore, obese adolescents with IGT will have larger adipocytes, while having significantly fewer adipocytes compared to obese adolescents with NGT. Obese adolescents with IGT will also have altered expression of key genes related to insulin resistance., and 4)Abnormalities in endothelial function as manifested by low FMD and PAT are already present in obese adolescents with IGT and are linked to insulin resistance.