Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three categories of highly active antiretroviral therapy (HAART)-associated major toxic effects have been identified: nucleoside-related toxic effects (e.g., neuropathy, myopathy, pancreatitis, hepatic steatosis, lactic acidosis, and possibly lipoatrophy), metabolic complications (e.g., fat redistribution, insulin resistance, and hyperlipidemia), and bone disease (e.g., osteopenia and/or osteoporosis). The toxic effects caused by nucleosides are hypothesized to be a result of mitochondrial injury and include myopathy, pancreatitis, liver failure, and lactic acidosis. Alterations in lactic acid metabolism range from common instances of asymptomatic lactic acidemia to rare occurrences of life-threatening lactic acidosis with hepatic steatosis. A metabolic syndrome consisting of lipodystrophy (i.e., fat redistribution), hyperlipidemia and insulin resistance has been observed, particularly with protease inhibitor treatment. Some additive interaction between protease inhibitors and nucleosides has also been described. The potential relationship of these metabolic abnormalities to increased risk of cardiovascular disease and diabetes has broad implications on long-term patient management. Lipodystrophy associated with HAART is generally accompanied by potentially serious abnormalities, including dyslipidemia (i.e., hypercholesterolemia and hypertriglyceridemia) and altered glucose metabolism (i.e., insulin resistance). Regimens of HAART may have adverse effects on bone metabolism, as indicated by emerging reports of osteopenia, osteoporosis, and avascular necrosis.
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PMID:Long-term exposure to lifelong therapies. 1183 99

The metabolic syndrome of chronic critical illness (CCI) consists of multisystem organ dysfunction resulting from the initial acute injury and chronic immune-neuroendocrine axis activation, adult kwashiorkor-like malnutrition, and prolonged immobilization with suppression of the PTH-vitamin D axis and hyper-resorptive metabolic bone disease. CCI patients can also present unique challenges in the management of diabetes mellitus, thyroid and adrenal diseases, electrolyte abnormalities and hypogonadism.
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PMID:Endocrine and metabolic issues in the management of the chronically critically ill patient. 1214 Sep 16

The natural history of inborn errors of protein metabolism and the long-term effects of prescribed semisynthetic therapeutic diets are largely unknown. We assessed body composition, measuring body-fat mass and distribution, fat-free mass, total body protein, total body potassium, bone density and skeletal muscle mass, in young adults (age > 18 years; 6 female, 5 male) with inborn errors of protein metabolism maintained on long-term low-protein diets, compared with controls. Female patients were significantly shorter (159.4 cm vs 169.2 cm, p = 0.013) and had higher BMI (25.3 vs 22.0 kg/m2, p < 0.05), abdominal to gluteal circumference ratio (0.84 vs 0.73, p = 0.011), percentage body fat (42.3% vs 29.5%, p < 0.005) and ratio of central to peripheral body fat (1.15 vs 0.86, p < 0.05) than controls. Male patients had lower height-adjusted total body bone mineral content (0.9 vs 1.02 g/m2, p < 0.04) and skeletal muscle mass (31.1 vs 36.3 kg, p < 0.04) than controls. Compared with controls, patients'nitrogen index was significantly lower (0.91 vs 1.03, p < 0.01), consistent with lower total body protein. Potassium index was significantly higher (121.2% vs 110.4%, p < 0.03), consistent with higher body cell mass, or intracellular water. Documentation of body composition in larger patient series is important to elucidate whether these results reflect increased risks (hence opportunities for prevention) of bone disease, metabolic syndrome and cardiovascular disease in this population.
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PMID:Body composition in young adults with inborn errors of protein metabolism--a pilot study. 1615 92

We have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreases the serum phosphate. Most recently, these observations were rediscovered in low-density lipoprotein receptor null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia, and insulin resistance). We had demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial type. We have shown that VC is worsened by CKD and ameliorated by bone morphogenetic protein -7 (BMP-7). The finding that high-fat-fed low-density lipoprotein receptor null animals without CKD have hyperphosphatemia led us to examine the skeletons of these mice. We found significant reductions in bone formation rates, associated with increased VC and superimposing CKD results in the adynamic bone disorder (ABD), while VC was worsened and hyperphosphatemia persisted. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. BMP-7 treatment corrected the ABD and corrected hyperphosphatemia, compatible with BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. Thus, in the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to ABD producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through increased bone formation and skeletal deposition of phosphate, and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury before demonstrable hyperphosphatemia, and they are preventable and treatable. Therefore, early intervention in CKD is warranted and may affect mortality of the disease.
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PMID:Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives. 1633 68

In two independent and separate studies, we have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreased the serum phosphate. In the first study, the serum Ca PO(4), parathyroid hormone (PTH), and calcitriol were maintained normal after renal ablation in mice, and even mild renal injury equivalent to stage 3 CKD decreased bone formation rates. More recently, these observations were rediscovered in low-density lipoprotein receptor null (LDLR-/-) mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia and insulin resistance). We demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial calcification. We have also shown that VC is made worse by CKD and ameliorated by bone morphogenetic protein-7 (BMP-7). The finding that high-fat fed LDLR-/- animals with CKD had hyperphosphatemia which was prevented in BMP-7-treated animals lead us to examine the skeletons of these mice. It was found that significant reductions in bone formation rates were associated with high-fat feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD), while VC was made worse. The effect of CKD to decrease skeletal anabolism (decreased bone formation rates and reduced number of bone modelling units) occurred despite secondary hyperparathyroidism. The BMP-7 treatment corrected the ABD and hyperphosphatemia, owing to BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in the metabolic syndrome with CKD, a reduction in bone forming potential of osteogenic cells leads to the ABD producing hyperphosphatemia and VC, processes ameliorated by BMP-7, in part through increased bone formation and skeletal deposition of phosphate and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury affecting the skeleton before demonstrable hyperphosphatemia and that they are preventable and treatable. Therefore, early intervention in the skeletal disorder associated with CKD is warranted and may affect mortality of the disease.
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PMID:Function and effect of bone morphogenetic protein-7 in kidney bone and the bone-vascular links in chronic kidney disease. 1688 97

A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that complicates the metabolic syndrome was produced. In this model, the metabolic syndrome is characterized by severe atherosclerotic plaque formation, hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD stimulates calcification of the neointima and tunica media of the aorta. The CKD in this model is associated the adynamic bone disorder form of renal osteodystrophy. The VC of the model is associated with hyperphosphatemia, and control of the serum phosphorus both in this animal model and in humans has been preventive in the development of VC. This article reports studies that demonstrate reduction of established VC by the addition of sevelamer carbonate to the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides normalizing the serum phosphorus, surprisingly, reversed the CKD-induced trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces and, importantly, bone formation rates. In addition, sevelamer was found to be effective in decreasing serum cholesterol levels. These results suggest that sevelamer may have important actions in decreasing diabetic and uremic vasculopathy and that sevelamer carbonate may be capable of increasing bone formation rates that are suppressed by diabetic nephropathy.
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PMID:Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. 1718 86

Cardiovascular morbidity and mortality complicates the course of a significant proportion of renal transplant recipients and is increasingly prevalent among recipients of other solid organ transplants, such as heart or liver transplant patients. A posttransplant metabolic syndrome comprised of hypertension, dyslipidemia, increased fat mass/obesity, and glucose intolerance, combined with other metabolic side effects derived from glucocorticoid and calcineurin inhibitor immunosuppression, attenuates allograft and patient survival. After the early posttransplant years, infection and rejection are the major risks that recipients face, whereas metabolic and cardiovascular disease become the most serious long term risk factors impacting patient survival. While significant advances in immunosuppressive therapy have prolonged the allograft and patient survival in solid organ transplant recipients, little has been done in the way of controlled interventional trials utilizing nutritional, dietary, or biobehavioral modification, especially when combined with drug treatment to reduce the effects of the posttransplant metabolic syndrome. In addition to cardiovascular morbidity, metabolic bone disease, osteopenia, and impaired growth in children pose significant challenges in posttransplant management. In this review, the data from some of the known observational dietary trials in solid organ transplant recipients and prior evidence obtained from studies in chronic kidney disease and the general population is considered in formulating new targets for future research to deal with this ever-increasing population of high risk patients.
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PMID:Nutritional and metabolic issues in solid organ transplantation: targets for future research. 1912 84

Vitamin D deficiency is a well-established risk factor for bone disease. Emerging data suggest a pleiotropic role of this agent in a variety of functions in humans. Epidemiological studies indicate an inverse association between vitamin D deficiency and the prevalence of cardiovascular disease (CVD), as well as individual cardiometabolic risk factors, such as hypertension, diabetes, dyslipidemia and the metabolic syndrome. Moreover, vitamin D deficiency has been implicated in the atherosclerotic process. This review considers current data regarding the role of vitamin D deficiency in the development of CVD and addresses the effect of supplementation on cardiovascular outcomes.
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PMID:Vitamin D and cardiovascular disease: a novel agent for reducing cardiovascular risk? 2018 Jul 65

Nephrolithiasis research and care have been focused on biochemical changes in urinary solute excretion leading to stone formation, but abnormalities in urine chemistry alone do not explain many aspects of the condition of patients with kidney stone disease. Evidence exists of an association with metabolic syndrome, obesity, diabetes and hypertension, and of enhanced risk of chronic kidney disease and metabolic bone disease. Very recently also a higher risk of cardiovascular events and damage has been reported in kidney stone formers when compared with non-stone formers. It is time to view nephrolithiasis as a condition predictive of chronic kidney disease and cardiovascular damage, which deserves full metabolic evaluation together with an early prevention care strategy, mainly consisting of dietary and lifestyle changes, in a multidisciplinary approach. Kidney stone disease should be considered as a systemic disorder with clinical relevance beyond symptomatic urinary tract obstruction.
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PMID:Update on nephrolithiasis: beyond symptomatic urinary tract obstruction. 2162 79

Technological innovations in the ICU have led to artificially prolonged life, with an associated cost. Chronic critical illness (CCI) occurs in patients with prolonged mechanical ventilation and allostatic overload, and is associated with a discrete and consistent metabolic syndrome. Metabolic interventions are extrapolated from clinical critical care research, scientific theory, and years of CCI patient care experience. Intensive metabolic support (IMS) is a multi-targeted approach consisting of tight glycemic control with intensive insulin therapy, early and adequate nutrition therapy, nutritional pharmacology, management of metabolic bone disease, and meticulous attention to other endocrine/metabolic derangements. Ideally, IMS should be under the supervision of a metabolic support consultative team. Further research specifically focused on the CCI population is needed to validate this current approach.
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PMID:Metabolic and nutrition support in the chronic critical illness syndrome. 2266 70


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