View clinical trials related to Insulin Resistance.
Filter by:Recently a common Greenlandic nonsense p.Arg684erTer variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 was discovered. The variant has an allele frequency of 17%. Homozygous carriers of this TBC1D4 variant have impaired glucose tolerance and a 10-fold enhanced risk of developing type 2 diabetes (T2D). The investigators propose to carry out comprehensive metabolic phenotyping of adult Inuits carrying zero or two alleles of the TBC1D4 variant. The investigators hypothesise that regulation of TBC1D4 in skeletal muscle is pivotal in regulating glucose uptake during exercise, during physiological insulin stimulation, and for the ability of an acute bout of exercise to improve insulin sensitivity to regulate glucose metabolism in humans. The overall aims in the present project are to: 1. Determine whether the TBC1D4 p.Arg684Ter variant affects the regulation of glucose uptake in skeletal muscle during exercise and during physiological insulin stimulation. 2. Determine the effect of the TBC1D4 p.Arg684Ter variant for the ability of acute exercise to insulin sensitize skeletal muscle to regulate glucose metabolism. 3. Define the metabolic pathways affected by the p.Arg684Ter variant in order to identify causal factors responsible for the diabetic phenotype of Inuit carriers. The knowledge generated will contribute to additional explanatory clues to the increased frequency of T2D in the carriers.
Two important mechanisms play a major role in the pathogenesis of type 2 diabetes: insulin resistance of the target tissues and the impaired insulin secretion from pancreatic β-cells. Postprandial factors (such as insulin) are perceived by the human brain and induce signals that regulate glucose metabolism via the parasympathetic nervous system. Deep breathing exercise can increase parasympathetic nerve activity. Heart rate variability (HRV) in healthy people can be significantly increased by deep breathing maneuvers, indicating a shift from sympathetic activity to parasympathetic activity. The hypothesis is that this postprandial shift results in a change in peripheral glucose metabolism. In turn, the increased parasympathetic activity could potentially result in a change in postprandial insulin sensitivity or secretion. To test this hypothesis, this study investigates the effect of deep breathing exercise versus normal breathing on insulin sensitivity, on insulin secretion, glucose tolerance, resting energy expenditure, and on parasympathetic tone (analysis of heart rate variability).
To compare the effect of insulin sensitizing drugs (metformin and rosiglitazone) over glucose homeostasis (GH) in no diabetic metabolic syndrome individuals. A randomized blinded clinical trial did in patients with metabolic syndrome (n=30), without diabetes. Prior to detailed information and signature of informed consent by patients were done three treatment groups by randomized technique; a) Placebo, b) Metformin (850 mg/day), c) Rosiglitazone (4 mg/day), treatment was administered for 8 weeks. GH was measured before and after treatment using oral glucose tolerance test (OGTT), and IR-index (Homeostatic Model). Determination was performed on weight, size, body mass index, plicometry, blood pressure, fasting glucose levels, triglycerides, HDL-cholesterol and insulin.
Counting Carbohydrates (CC) is the preferable method used to calculate the amount of insulin needed for a meal. This method is employed by patients with type 1 diabetes melitus (T1DM). the patients receive the general arithmetic calculation of how much insulin to inject for 15 grams/1 portion of carbohydrate (carb to insulin ratio (C:I) and insulin sensitivity (IS). However, Diabetes Educators are often confronted with difficulties guiding their T1DM patient when using this method and find patients get confused calculating the amount of carbs needed. The investigators sought to create a simple tool that would help our patients implement the CC method easily and properly.
Previous work of the investigators demonstrated the anti-obesity and anti-steatosis potential of the Amazonian fruit camu-camu (CC) in a mouse model of diet-induced obesity [1]. It was demonstrated that the prebiotic role of CC was directly linked to higher energy expenditure stimulated by the fruit since fecal transplantation from CC-treated mice to germ-free mice was sufficient to reproduce the effects. The full protection against hepatic steatosis observed in CC-treated mice is of particular importance since nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. Thirty percent of adults in developed countries have excess fat accumulation in the liver, and this figure can be as high as 80% in obese subjects. NAFLD is an umbrella term encompassing simple steatosis, as well as non-alcoholic steatohepatitis which can lead to cirrhosis and hepatocellular carcinoma in up to 20% of cases. Up to now, except for lifestyle changes, no effective drug treatment are available. Previous work has suggested that CC possesses anti-inflammatory properties and could acutely reduce blood pressure and glycemia after a single intake. While CC could represent a promising treatment for obesity and fatty liver, no studies have thoroughly tested this potential in humans. Therefore, a robust clinical proof of concept study is needed to provide convincing evidence for a microbiome-based therapeutic strategy to counteract obesity and its associated metabolic disorders. The mechanism of action of CC could involve bile acid (BA) metabolism. BA are produced in the liver and metabolized in the intestine by the gut microbiota. Conversely, they can modulate gut microbial composition. BA and particularly, primary BA, are powerful regulators of metabolism. Indeed, mice treated orally with the primary BA α, β muricholic (αMCA, βMCA) and cholic acids (CA) were protected from diet-induced obesity and hepatic lipid accumulation. Interestingly, the investigators reported that administration of CC to mice increased the levels of αMCA, βMCA and CA. Primary BA are predominantly secreted conjugated to amino acids and that deconjugation rely on the microbial enzymatic machinery of gut commensals. The increased presence of the deconjugated primary BA in CC-treated mice indicate that a cluster of microbes selected by CC influence the BA pool composition. These data therefore point to an Interplay between BA and gut microbiota mediating the health effects of CC. Polyphenols and in particular procyanidins and ellagitannins in CC can also be responsible for the modulation of BA that can impact on the gut microbiota. Indeed, it has been reported that ellagitannins containing food like walnuts modulate secondary BA in humans whereas procyanidins can interact with farnesoid X receptors and alter BA recirculation to reduce hypertriglyceridemia. These effects are likely mediated by the remodeling of the microbiota by the polyphenols. In accordance with the hypothesis that the ultimate effect of CC is directly linked to a modification of the microbiota, fecal transplantation from CC-treated mice to germ-free mice was sufficient to recapitulate the lower weight gain and the higher energy expenditure seen in donor mice.
The overarching goal of this proposal is to determine whether DNA methylation of the mitochondrial DNA impairs mitochondrial function in insulin resistant states such as overweight/obesity and type 2 diabetes.
It has been suggested that the actual obesity epidemy is related to chronic overconsumption of added or free sugars. The increasing popularity of artificial sweeteners attest the population willingness to reduce added sugars intake and to use alternatives to alleviate health impact of free sugar overconsumption. However, recent findings suggest that artificial sweeteners may rather contribute to obesity epidemy and its associated adverse health effects, potentially via a negative impact on gut microbiota. It has been shown in various studies that, for the same amount of sucrose, unrefined sugars (such as maple syrup) are associated with favorable metabolic effects. The polyphenols contained in maple syrup, especially lignans, could contribute to these positive effects. Indeed, the strong impact of those biomolecules on the modulation of gut microbiota and on gastro-intestinal and metabolic health has been demonstrated in several studies. It is therefore highly relevant to test the hypothesis that the substitution of refined sugar by an equivalent amount of maple syrup (5% of daily energy intake) result in a lesser metabolic deterioration, by the modulation of maple syrup on gut microbiota, than the one observed with refined sugar.
The investigators believe that the emerging epidemiological evidence connecting topical use of corticosteroids to the development of type 2 diabetes and osteoporosis point to potentially massive, yet clinically unacknowledged problems associated with topical corticosteroid treatment. Using state-of-the-art methodology, the present study will delineate the impact of topical corticosteroid use on insulin sensitivity and bone turnover markers in patients with atopic dermatitis and, thus, provide important data that may have implications for millions of people using topical corticosteroids.
There is evidence that genistein present in soy can improve insulin resistance in rodents and humans with metabolic syndrome (MetS). However, it is not known if this improvement is associated with changes in the gut microbiota. In the present study, the investigators show that the consumption of genistein for 2 months could have an effect on insulin resistance in subjects with MetS. This effect will be accompanied by a modification of the gut microbiota taxonomy. As a consequence, there will be a reduction in metabolic endotoxemia accompanied by an increase in AMP-activated protein kinase (AMPK) phosphorylation and the expression of genes of fatty acid oxidation in skeletal muscle.
Regulation of mitochondrial health in overweight and obese individuals may be impaired. The purpose of this study is to identify impairments in regulation of mitochondrial health within skeletal muscle and to determine if short-term exercise training (2-weeks) can reverse such impairments. The investigator's hypothesis is that pathways that serve to degrade poorly functioning mitochondria in overweight and obese individuals are down-regulated, but that short-term exercise training can restore these pathways to improve skeletal muscle mitochondrial function.