1,721,058 research outputs found
Andrew J. Krentz, Lutz Heinemann, Marcus Hompesch (Eds). Translational Research Methods for Diabetes, Obesity and Cardiometabolic Drug Development: A Focus on Early Phase Clinical Studies
No full textType 2 diabetes mellitus (T2DM) is one of the greatest public health problems worldwide.
Adults with T2DM are more likely to have heart diseases or a stroke than adults without
diabetes, and cardiovascular diseases account for more than 50% of deaths in T2DM [1].
The risk of macroand microvascular events and mortality are all strongly associated with
hyperglycemia, and epidemiological data suggest that an increase of 1% in glycated
hemoglobin (HbA1c) corresponds to an increase of approximately 18% in the risk for ..
Role of anatomical location, cellular phenotype and perfusion of adipose tissue in intermediary metabolism: A narrative review
No full textIt is well-established that adipose tissue accumulation is associated with insulin resistance through multiple mechanisms. One major metabolic link is the classical Randle cycle: enhanced release of free fatty acids (FFA) from hydrolysis of adipose tissue triglycerides impedes insulin-mediated glucose uptake in muscle tissues. Less well studied are the different routes of this communication. First, white adipose tissue depots may be regionally distant from muscle (i.e., gluteal fat and diaphragm muscle) or contiguous to muscle but separated by a fascia (Scarpa’s fascia in the abdomen, fascia lata in the thigh). In this case, released FFA outflow through the venous drainage and merge into arterial plasma to be transported to muscle tissues. Next, cytosolic triglycerides can directly, i.e., within the cell, provide FFA to myocytes (but also pancreatic ß-cells, renal tubular cells, etc.). Finally, adipocyte layers or lumps may be adjacent to, but not anatomically segregated, from muscle, as is typically the case for epicardial fat and cardiomyocytes. As regulation of these three main delivery paths is different, their separate contribution to substrate competition at the whole-body level is uncertain. Another important link between fat and muscle is vascular. In the resting state, blood flow is generally higher in adipose tissue than in muscle. In the insulinized state, fat blood flow is directly related to whole-body insulin resistance whereas muscle blood flow is not; consequently, fractional (i.e., flow-adjusted) glucose uptake is stimulated in muscle but not fat. Thus, reduced blood supply is a major factor for the impairment of in vivo insulin-mediated glucose uptake in both subcutaneous and visceral fat. In contrast, the insulin resistance of glucose uptake in resting skeletal muscle is predominantly a cellular defect
Relationship between impaired glucose tolerance, noninsulin-dependent diabetes mellitus and obesity
No full textPlasma glucose concentration is the best predictor for the development of non-insulin-dependent diabetes mellitus (NIDDM). However, obesity is also a recognized risk factor for development of the disease, and is easier to track over time. Thus obesity could be of considerable clinical importance as a predictor of diabetes. Studies have shown that the degree of overweight, the change in weight and the duration of overweight are all separate predictors of diabetes. The British Regional Heart Study showed that an increasing body mass index (BMI) was associated with increased risk of developing diabetes, even at BMI values not considered obese. A separate study showed that weight gain increased the risk of diabetes independently of BMI, while weight loss decreased the risk. The duration of obesity was also an important factor in developing NIDDM. A long duration increased the risk of diabetes, irrespective of the final BMI value. The effects of obesity on insulin action have also been investigated. Studies have shown that insulin sensitivity is inversely related to insulin secretion, with a disproportionate increase in insulin secretion seen with decreasing sensitivity. A recent European study showed that the prevalence of both insulin hypersecretion and insulin resistance increased with increasing BMI. Thus, in obesity, higher insulin levels are necessary to maintain glucose tolerance, leading to increased stress on the β-cells. In obese individuals, weight loss improved insulin sensitivity in proportion to the degree of weight loss, leading to decreased insulin secretion. Weight loss can therefore, at least in the short term, act to decrease the risk of developing diabetes by reducing insulin resistance, and thus relieving β-cell stress, the factor ultimately responsible for hyperglycaemia in predisposed individuals
Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation.
No full textBariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB-less after SG-bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review
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