Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.

STATIN-INDUCED MECHANISMS OF CARBOHYDRATE METABOLISM DISORDERS

Statins are first-line medications that are used to prevent cardiovascular diseases. They reduce the risk of myocardial infarction, stroke, and cardiovascular death by an average of 25-30%. Despite the safety and relative tolerability of statins, observational and clinical studies as well as meta-analyses have shown that statins may increase the risk of developing type 2 diabetes mellitus. Statins have been proven to increase insulin resistance and reduce insulin secretion by pancreatic β-cells

Evaluation of organ glucose metabolism by 18F-FDG accumulation with insulin loading in aged mice compared with young normal mice

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

Evaluation of the potential of organ glucose metabolism by 18F-FDG accumulation with insulin loading in super-aged mice compared with young normal mice

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-D-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in super-aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in super-aged and young wild-type mice. In control groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the super-aged mice. After insulin loading, the 18F-FDG accumulation levels showed negative changes in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the super-aged mice, whereas positive changes were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the super-aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

The influence of growth hormone therapy on the cardiovascular system in Turner syndrome

Short stature, ovarian dysgenesis, infertility, and cardiovascular malformations are classic features in Turner syndrome (TS), but the phenotypical spectrum is wide. Through early diagnosis and appropriate treatment, TS patients have a chance to achieve satisfactory adult height and sexual development. The doses of recombinant growth hormone (rGH) used are usually higher than the substitution dose. The safety aspects of this therapy are very important, especially in terms of the cardiovascular system. The presented study aimed to analyze how the rGH therapy may influence the cardiovascular system in TS based on current literature data. We conducted a systematic search for studies related to TS, cardiovascular system, and rGH therapy. The results show that rGH seems to have a positive effect on lipid parameters, reducing the risk of ischemic disease. It is additionally optimized by estradiol therapy. Although rGH may increase insulin resistance, the metabolic derangement is rare, probably due to lower fat content and an increase in lean body mass. Several studies showed that rGH treatment could cause aorta widening or increase the aorta growth rate. IGF-1 can be independently associated with increased aortic diameters. The studies analyzing the impact of GH on blood pressure show conflicting data. The proper cardiovascular imaging before and during rGH treatment and detecting the known risk factors for aorta dissection in every individual is very important. The long-term effects of growth hormone treatment on the heart and arteries are still not available and clearly estimated and have to be monitored in the future.