Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoids, when administered over prolonged periods of time, cause protein wasting, osteoporosis, elevation of total cholesterol, and carbohydrate intolerance. Human GH is a potent anabolic agent known to stimulate protein synthesis and osteoblast activity. Chronic hypercortisolemia is associated with impaired GH secretion. The aim of our study was to evaluate the effects of short term administration of human recombinant GH on bone and fuel metabolism in patients receiving chronic glucocorticoid treatment and with suppressed GHRH-stimulated GH peaks (< 10 micrograms/L). We studied nine nonobese adult patients more than 70 yr of age (seven females and two males; age range, 41-68 yr; body mass index, 26 +/- 1.3 kg/m2) undergoing long term glucocorticoid therapy for nonendocrine diseases. After a 3-day stabilization period in the hospital, several parameters were evaluated in all patients: 1) protein, 2) bone, 3) lipid, 4) carbohydrate metabolism, and 5) immune system function under baseline conditions. At 1800 h on the fifth day of hospitalization, the patients began treatment with a daily sc injection of 0.1 IU/kg (0.037 mg/kg) recombinant human GH (Humatrope, Eli Lilly Co.) for 7 days. GH administration caused a significant increase in nitrogen balance (from -0.12 +/- 0.04 to -0.03 +/- 0.02 g/kg.day; P < 0.05), osteocalcin, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal telopeptide of type I collagen with respect to basal levels. After GH administration, total, high density lipoprotein, and low density lipoprotein cholesterol levels were significantly lowered, and serum triglyceride levels were increased in all patients. Normal blood glucose levels during GH administration were observed in our patients concomitantly with a slight increase in insulin secretion. After GH treatment, the T-helper/T-suppressor cell ratio significantly increased with respect to basal levels (2.5 +/- 0.4 vs. 2.2 +/- 0.3; P < 0.05). Our data suggest that in patients receiving chronic glucocorticoid treatment, GH administration may significantly antagonize several side-effects of long term glucocorticoid administration, such as protein wasting, osteoporosis, and hyperlipidemia.
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PMID:Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone. 782

A thyroid hormone analog with organ-selective effects could have therapeutic application for disorders such as hyperlipidemia and osteoporosis. We performed a randomized clinical trial to determine the specific thyromimetic effects of tiratricol. Twenty-four athyreotic patients underwent detailed metabolic and physiological evaluation after a 2-month baseline period, taking TSH-suppressive doses of L-T4. They were then randomized to blinded treatment with either tiratricol (24 micrograms/kg twice daily) or L-T4 (1.9 micrograms/kg daily). The dose of hormone was increased until the TSH level was less than 0.1 mU/L, and the metabolic and physiological testing was repeated. Comparing the change from baseline to the study drug periods, when serum TSH levels were equivalently suppressed, there were no significant differences between the two groups in resting metabolic rate, weight, urea nitrogen excretion, or symptom score. Plasma total and low density lipoprotein cholesterol levels declined 13 +/- 4% and 23 +/- 6% in the tiratricol group compared with 2 +/- 2% and 5 +/- 3% in the L-T4 group (P = 0.015 and P = 0.0066, respectively). Serum sex hormone-binding globulin levels increased 55 +/- 13% with tiratricol compared with a 1.7 +/- 4% decline with L-T4 (P = 0.0006), indicating an augmented hepatic response to tiratricol. Skeletal metabolic activity was enhanced, with increased levels of serum osteocalcin and urinary excretion of calcium and pyridinium cross-links. Tiratricol and L-T4 had comparable effects on cardiovascular function. Tiratricol has distinct augmented hepatic and skeletal thyromimetic actions of potential therapeutic value.
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PMID:Augmented hepatic and skeletal thyromimetic effects of tiratricol in comparison with levothyroxine. 921 87

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.
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PMID:Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis. 1151 Sep 16

Artery calcification occurring in atherosclerosis is connected with a high risk of cardiovascular events. Quantitative calcification evaluation using electron beam tomography indicated a correlation between artery calcification and well-known cardiovascular risk factors, i.e. smoking, obesity, and hyperlipidemia. Elevated calcium scores are especially observed in diabetic patients, which may even explain the higher mortality in this group. Calcification leads to increased blood vessel rigidity and, consequently, elevated arterial vascular resistance and left ventricular hypertrophy. An increased risk of plaque rupture in relation to calcium-rich atherosclerotic lesions was not proved. Plaque rupture and thromboembolitic complications are probably higher in the case of lipid-rich lesions. Atherosclerotic calcification is an active process in which many cells (monocytes/macrophages, vascular smooth muscle cells, and endothelial cells) participate. Many substances and transcription factors normally participating in the bone remodeling process are found in calcified atherosclerotic lesions (e.g. Cbfa-1, osteocalcin, alkaline phosphatase, BMP-2, osteopontin, osteoprotegrin, and RANKL). On monocytes, cells playing an important role in atherosclerosis progression, the presence of a calcium-sensing receptor (CaR) has been demonstrated. Increase in monocyte chemotaxis and increased interleukin 6 secretion in response to extracellular calcium were observed. Monocytes also directly and indirectly enhance vascular calcification. Immune cells and cytokines participating in vascular calcification are connected in one pathogenetic mechanism, i.e. atherosclerosis as an inflammatory disease and calcification.
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PMID:[The role of calcium ions in the pathomechanism of the artery calcification accompanying atherosclerosis]. 1576 85

Vascular calcification is often encountered in advanced atherosclerotic lesions and is a common consequence of aging. Calcification of the coronary arteries has been positively correlated with coronary atherosclerotic plaque burden, increased risk of myocardial infarction, and plaque instability. Chronic kidney disease (CKD) patients have two to five times more coronary artery calcification than healthy age-matched individuals. Vascular calcification is a strong prognostic marker of cardiovascular disease mortality in CKD patients. Vascular calcification has long been considered to be a passive, degenerative, and end-stage process of atherosclerosis and inflammation. However, recent evidence indicates that bone matrix proteins such as osteopontin, matrix Gla protein (MGP), and osteocalcin are expressed in calcified atherosclerotic lesions, and that calcium-regulating hormones such as vitamin D3 and parathyroid hormone-related protein regulate vascular calcification in in vitro vascular calcification models based on cultured aortic smooth muscle cells. These findings suggest that vascular calcification is an actively regulated process similar to osteogenesis, and that bone-associated proteins may be involved in the development of vascular calcification. The pathogenesis of vascular calcification in CKD is not well understood and is almost multifactorial. In CKD patients, several studies have found associations of both traditional risk factors, such as hypertension, hyperlipidemia, and diabetes, and uremic-specific risk factors with vascular calcification. Most patients with progressive CKD develop hyperphosphatemia. An elevated phosphate level is an important risk factor for the development of calcification and cardiovascular mortality in CKD patients. Thus, it is hypothesized that an important regulator of vascular calcification is the level of inorganic phosphate. In order to test this hypothesis, we characterized the response of human smooth muscle cell (HSMC) cultures to inorganic phosphate levels. Our findings indicate that inorganic phosphate directly regulates HSMC calcification through a sodium-dependent phosphate transporter mechanism. After treatment with elevated phosphate, there is a loss of smooth muscle lineage markers, such as alpha-actin and SM-22alpha, and a simultaneous gain of osteogenic markers such as cbfa-1 and osteocalcin. Elevated phosphate may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification, and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. Furthermore, putative calcification inhibitory molecules have been identified using mouse mutational analyses, including MGP, beta-glucosidase, fetuin-A, and osteoprotegerin. Mutant mice deficient in these molecules present with enhanced cardiovascular calcification, demonstrating that specific molecules are normally important in suppressing vascular calcification. These findings suggest that the balance of inducers, such as phosphate, and inhibitors, such as MGP, fetuin-A, and others, are likely to control whether or not calcification occurs under pathological conditions.
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PMID:Vascular calcification in chronic kidney disease. 1650 29

Diabetes type I is associated with bone loss and increased bone adiposity. Osteoblasts and adipocytes are both derived from mesenchymal stem cells located in the bone marrow, therefore we hypothesized that if we could block adipocyte differentiation we might prevent bone loss in diabetic mice. Control and insulin-deficient diabetic BALB/c mice were chronically treated with a peroxisomal proliferator-activated receptor gamma (PPARgamma) antagonist, bisphenol-A-diglycidyl ether (BADGE), to block adipocyte differentiation. Effects on bone density, adiposity, and gene expression were measured. BADGE treatment did not prevent diabetes-associated hyperglycemia or weight loss, but did prevent diabetes-induced hyperlipidemia and effectively blocked diabetes type I-induced bone adiposity. Despite this, BADGE treatment did not prevent diabetes type I suppression of osteoblast markers (runx2 and osteocalcin) and bone loss (as determined by micro-computed tomography). BADGE did not suppress osteoblast gene expression or bone mineral density in control mice, however, chronic (but not acute) BADGE treatment did suppress osteocalcin expression in osteoblasts in vitro. Taken together, our findings suggest that BADGE treatment is an effective approach to reduce serum triglyceride and free fatty acid levels as well as bone adiposity associated with type I diabetes. The inability of BADGE treatment to prevent bone loss in diabetic mice suggests that marrow adiposity is not linked to bone density status in type I diabetes, but we cannot exclude the possibility of additional BADGE effects on osteoblasts or other bone cells, which could contribute to preventing the rescue of the bone phenotype.
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PMID:Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss. 1697 49

Cardiovascular disease, such as atherosclerosis, has been associated with reduced bone mineral density and fracture risk. A major etiologic factor in atherogenesis is believed to be oxidized phospholipids. We previously found that these phospholipids inhibit spontaneous osteogenic differentiation of marrow stromal cells, suggesting that they may account for the clinical link between atherosclerosis and osteoporosis. Currently, anabolic agents that promote bone formation are increasingly used as a new treatment for osteoporosis. It is not known, however, whether atherogenic phospholipids alter the effects of bone anabolic agents, such as bone morphogenetic protein (BMP)-2 and parathyroid hormone (PTH). Therefore we investigated the effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on osteogenic signaling induced by BMP-2 and PTH in MC3T3-E1 cells. Results showed that ox-PAPC attenuated BMP-2 induction of osteogenic markers alkaline phosphatase and osteocalcin. Ox-PAPC also inhibited both spontaneous and BMP-induced expression of PTH receptor. Consistently, pretreatment of cells with ox-PAPC inhibited PTH-induced cAMP production and expression of immediate early genes Nurr1 and IL-6. Results from immunofluorescence and Western blot analyses showed that inhibitory effects of ox-PAPC on BMP-2 signaling were associated with inhibition of SMAD 1/5/8 but not p38-MAPK activation. These effects appear to be due to ox-PAPC activation of the ERK pathway, as the ERK inhibitor PD98059 reversed ox-PAPC inhibitory effects on BMP-2-induced alkaline phosphatase activity, osteocalcin expression, and SMAD activation. These results suggest that atherogenic lipids inhibit osteogenic signaling induced by BMP-2 and PTH, raising the possibility that hyperlipidemia and atherogenic phospholipids may interfere with anabolic therapy.
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PMID:Atherogenic phospholipids attenuate osteogenic signaling by BMP-2 and parathyroid hormone in osteoblasts. 1752 49

The Spontaneously Diabetic Torii-Lepr(fa) (SDT- fa/fa) rat is a new model of obese type 2 diabetes. The female SDT-fa/fa rat shows obesity, hyperglycemia and hyperlipidemia from a young age. However, it is not known whether diabetes and estrogen deficiency can lead to bone abnormalities in the female SDT-fa/fa rat. The objective of the present study was to investigate the effects of ovariectomy (OVX) on bone metabolism and bone mineral density (BMD) in the female SDT-fa/fa rat. Female Sprague-Dawley rats were used as control animals. The BMDs of the whole tibia and fifth lumbar (L5) vertebral body were analyzed at 30 weeks after OVX. Serum osteocalcin, a bone formation marker, and urine deoxypyridinoline (DPD), a bone resorption marker, were sequentially analyzed before and at 5, 15 and 30 weeks after OVX. Serum osteocalcin and urine DPD levels were lower in SDT-fa/fa rats than in control rats before OVX. Both serum osteocalcin and urine DPD levels were elevated in control rats 5-30 weeks after OVX, but only the urine DPD levels were elevated in SDT-fa/fa rats 5-30 weeks after OVX. SDT-fa/fa rats showed a decrease in the BMDs of the whole tibia and L5 vertebral body compared with control rats. OVX decreased the BMDs of the whole tibia and L5 vertebral body in control rats, but not in SDT-fa/fa rats. These data suggest that estrogen deficiency is not a risk factor for bone loss in type 2 diabetes mellitus.
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PMID:Effects of ovariectomy on bone metabolism and bone mineral density in spontaneously diabetic Torii-Lepr(fa) rats. 2149 Apr 14

The number of patients with osteoporosis or type 2 diabetes mellitus (T2DM) is increasing in aging and westernized societies. Both disorders predispose elderly people to disabling conditions by causing fractures and vascular complications, respectively. Recent animal studies have shown that administration of osteocalcin, which is specifically secreted from osteoblasts, can increase insulin secretion and ameliorate hyperglycemia, obesity, and high triglyceride levels in mice fed a high-fat diet. Moreover, several studies have shown that antagonism of Wnt signaling by oxidative stress contributes to the development of osteoporosis, as well as insulin resistance and hyperlipidemia. Thus, bone metabolism and glucose/fat metabolism seem to be etiologically related to each other. Meta-analyses of multiple clinical studies in humans have shown that hip fracture risk of T2DM patients is increased by 1.4-1.7-fold, although bone mineral density (BMD) is not diminished. Vertebral fracture risk of T2DM patients is also increased, and BMD is not sensitive enough to assess the risk. These findings suggest that bone fragility in T2DM, which is not reflected by BMD, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. Pentosidine, the endogenous secretory receptor for advanced glycation endproducts, and insulin-like growth factor-I seem to be such candidates, although further studies are required to clarify whether or not these markers could predict the occurrence of new fractures of T2DM patients in a prospective fashion.
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PMID:Bone fragility in type 2 diabetes mellitus. 2247 21

The aim of the work was to study the influence of statins on the functional and metabolic state of bone tissue during correction of type IIA and IIB hyperlipidemia in women with osteopenia. 53 of the 83 patients aged 45-50 years were treated with statins (20 mg/d) and low-fat diet. Bone mineral density (BMD) was measured in the lumbar spine region (LII-LIV) and femoral neck by DEXA. Simultaneously the lipid profile and serum bone metabolism markers (osteocalcin, beta-CrossLaps CL) were detected. Simvastatin therapy led to normalization of osteocalcin level (p<0.01) within 6 months. In the control group, it remained unaltered and tended to decrease after 12 months (p>0.05). The level of bone resorption marker (CL) dropped within 3 months after the onset of therapy (p<0.050) and continued to decrease by the 12th month (p<0.05). It was significantly lower than in controls (p<0.05) both after 6 and 12 months. BMD in the femoral neck and LII-LIV increased by 2.2 and 2.6% respectively after 12 months of simvastatin therapy and by 1.4 and 1.7% after consumption of low-fat diet. It is concluded that simvaststin therapy (20 mg/d) during 12 months has positive effect on bone metabolism during treatment of atherogenic hyperlipidemia in patients with osteopenia.
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PMID:[Experience with simvastatin therapy for the achievement of osteoprotective effects in women with hyperlipidemia]. 2321 15


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