Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility.
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PMID:Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. 1582 89

To clarify the pathogenesis of altered bone metabolism in diabetic state and its underlying mechanisms, the bone mineral content and fasting levels of serum intact parathyroid hormone (i-PTH), intact osteocalcin (i-OC), tartrate-resistant acid phosphatase (TRAP) and osteoclastgenesis inhibitory factor/osteoprotegerin (OCIF/OPG) were measured in male type 2 diabetic patients and their age-matched controls. In addition, urine levels of osteoclastic markers, C-telopeptide of type I collagen (CTx), deoxypyridinoline (DPD), and N-telopeptide of type I collagen (NTx) were simultaneously determined. Serum levels of i-PTH and i-OC in diabetic patients were significantly lower than those in the controls. Conversely, serum concentrations of TRAP were significantly elevated in diabetic patients. However, no clear correlation was observed between serum i-OC and TRAP. It was also observed that urinary excretion of CTx, DPD, and NTx was significantly increased in the diabetics as compared with the controls. Unexpectedly, serum levels of OCIF/OPG tended to be higher in the diabetic group, and these values exhibited a significantly positive correlation with those of serum TRAP. There was found a significantly negative correlation between serum TRAP and bone mineral density (BMD) and also between serum OCIF/OPG and bone mineral density. It seems probable that OCIF/OPG has a suppressive role on the increased bone resorption to prevent further loss of the skeletal bone mass in type 2 diabetic patients.
Diabetes Res Clin Pract 2005 May
PMID:Osteoclastic function is accelerated in male patients with type 2 diabetes mellitus: the preventive role of osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density. 1586 Feb 39

In this study, we aimed to compare bone calcium system changes from children with diabetic ketoacidosis or acute metabolic acidosis due to dehydration to find out the relative contribution of metabolic acidosis and diabetes-related factors on expected negative calcium balance. We studied a set of non-invasive parameters of bone remodeling in 16 children with diabetic ketoacidosis due to new onset type 1 diabetes and 25 children with acute metabolic acidosis due to dehydration complicating acute gastroenteritis before and after the correction of acidosis. The two groups of subjects were matched for age, sex, pubertal status, and degree of metabolic acidosis and dehydration. A group of 18 age and sex-matched healthy children served as the control group. Plasma ionized calcium levels were increased in both groups, significantly more so in diabetic ketoacidosis. While osteoblastic markers, osteocalcin and alkaline phosphatase, were depressed to a comparable degree in both groups, urinary calcium/creatinine ratio and hydroxyproline excretion were significantly greater in diabetic ketoacidosis. No significant changes in calcitrophic hormone (intact PTH, calcitonin, 25-hydroxy vitamin D3) levels were observed. All study parameters except for serum phosphate levels behaved in parallel in both clinical conditions, and abnormalities disappeared with the correction of acidosis except for IGF-1, which remained low in diabetic subjects. In conclusion, our results suggest that, in diabetic ketoacidosis, the observed severe negative calcium balance occurred through diminished bone formation mediated by metabolic acidosis per se and increased bone mineral dissolution and bone resorption because of severe insulin deficiency and secondarily via metabolic acidosis. Observed changes appear to be independent of calcitrophic hormones.
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PMID:Bone calcium changes during diabetic ketoacidosis: a comparison with lactic acidosis due to volume depletion. 1586 25

It is well-known that secondary hyperparathyroidism of uremia influences not only bone and mineral metabolism but also cardiovascular complications. Here we reported the effects of the level of serum intact PTH and its gene polymorphism on cardiovascular and non-cardiovascular mortality in hemodialysis patients. We analyzed the association between clinico-molecular parameters and 3-year survival in 508 hemodialysis patients among whom 90 patients died. The multivariate Cox proportional hazards models showed that the presence of diabetes mellitus, levels of albumin and intact PTH, and BstB I genotype were indicated as independent predictors of cardiovascular mortality, whereas age and albumin level were indicated as those of non-cardiovascular mortality, suggesting that the level of intact PTH and its gene polymorphism effect cardiovascular mortality in hemodialysis patients.
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PMID:[Effects of parathyroid hormone gene polymorphism on cardiovascular mortality]. 1627 40

Cytomegalovirus (CMV) infection alone or in combination with other pathogens ("pathogen burden") has been postulated as a factor producing arteriosclerosis in some solid organ transplant recipients. The aim of this study was to assess whether the patients with CMV replication and/or "herpesvirus burden" experienced a greater incidence of cardiovascular events during the first year after kidney transplantation. One hundred twenty-one consecutive transplant recipients were prospectively studied for CMV replication using antigenemia and polymerase chain reaction (PCR) weekly during the 4 first months, and monthly thereafter for 1 year. Simultaneously, nested-PCR for human herpes virus (HHV)-6 and HHV-7 were performed to yield a herpesvirus burden (as determined by seropositivity), including CMV, herpes simplex virus (HSV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). The following additional parameters were analyzed: gender, age, smoking, duration of dialysis, preexistent diabetes, and preexistent cardiovascular events. After 1 year posttransplantation cardiovascular events, body mass index, arterial hypertension, number of antihypertensive drugs, use of ACE and/or ARBs inhibitors, diabetes, anemia, homocysteine, creatinine, cholesterol, HDLc, LDLc, PTH-i, proteinuria, and immunosuppression with cyclosporine or tacrolimus. CMV replication was present in 79 (65.3%) patients. Among 121 renal transplant recipients, 13 presented cardiovascular events, all associated with CMV replication (P = .004). Neither HHV-6 or HHV-7 replication influenced this complication. All patients with these events were seropositive for CMV, HSV, VZV, and EBV, as opposed to 64.8% without them (P = .009). Other factors that showed differences between patients with versus without events were as follows: preexistent events (76.9% vs 14.8%; P = .000), age (60 +/- 10 vs 49 +/- 14; P = .002), serum triglyceride value (191 +/- 82 vs 135 +/- 72; P = .02), and anemia (23.1% vs 5.6%; P = .05). Multiple logistic regression analysis for statistically significant variables only showed that preexistent events influenced the development of posttransplantation events (odds ratio, 27; 95% confidence interval, 4.7-154; P = .0005). In conclusion, cardiovascular events within 1 year after transplantation were more frequent among patients with CMV replication and seropositivity for other herpesviruses. An important risk factor was the presence of preexistent events.
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PMID:Cytomegalovirus replication and "herpesvirus burden" as risk factor of cardiovascular events in the first year after renal transplantation. 1638 30

The aim of the present study was to assess the role of cardiovascular risk factors in the occurrence of cardiovascular events among 100 consecutive renal transplant recipients during the first 2 years after transplantation. The following parameters were analyzed: (1) demographic data (gender, age, dialysis duration, preexistent diabetes, and pretransplantation events) as well as (2) basal 1-year, and 2-year posttransplantation data for events, body mass index, arterial hypertension, number of drugs for hypertension control, use of ACE or ARA II inhibitors, treatment with lipid- lowering drugs, de novo diabetes, anemia, immunosuppression with cyclosporine versus tacrolimus, and homocysteine, folic acid, serum creatinine, uric acid, PTH-i, and cholesterol total, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels. At the end of the second posttransplantation year, 14 patients versus 86 who did not experience a new cardiovascular event. Patients in the event group had more events pretransplantation and during the first posttransplantation year than those in the non event group (57.1% vs 17.4%; P = .003 and 78.6% vs 2.3%; P = .000, respectively). Furthermore, the former cohort of patients were older, had greater ventricular hypertrophy and had higher triglyceride and serum creatinine concentrations during the 2 years after transplantation. A multiple logistic regression analysis confirmed the relationship between events within 1 year of transplantation and serum creatinine level at the end of 2 years as well as the development of cardiovascular disease within 2 years. In conclusion, our data suggest the need for aggressive intervention during the first year to prevent the development of new cardiovascular events. Renoprotective strategies may also contribute to reduce the cardiovascular risk of renal transplant recipients.
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PMID:Risk factors for cardiovascular disease during the first 2 years after renal transplantation. 1638 36

Patients with primary hyperparathyroidism (PHPT) have impaired vasodilation both dependent and independent of endothelium. The aims of our study were to measure three different biochemical markers of endothelial activation, i. e., plasma thrombomodulin, soluble(s) E-selectin, and von Willebrand factor, in PHPT patients before and one year after successful parathyroidectomy, and to distinguish the potential effect of hypercalcemia and/or high parathyroid hormone from that of major cardiovascular risk factors (diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking habit) on endothelial function. Twenty consecutive patients with PHPT subdivided into two groups according to the absence (n = 8) or presence (n = 12) of one or more risk factors, and fifteen healthy normocalcemic subjects were studied. Baseline thrombomodulin levels were similar in the groups with and without risk factors, and in controls. In contrast, sE-selectin and von Willebrand factor were higher in PHPT patients with risk factors than in those without risk factors (p < 0.05 and p < 0.01, respectively) and controls (p < 0.01). Neither thrombomodulin nor sE-selectin changed after parathyroidectomy in either PHPT group. Plasma von Willebrand factor decreased (p < 0.01) in patients without risk factors, while persisting at high levels in patients with risk factors. In conclusion, in spite of a limitation due to the small number of patients, our study suggests that classic cardiovascular risk factors seem to be the main determinants for the high plasma levels of sE-selectin and vWF in PHPT. Together with unaltered thrombomodulin and sE-selectin levels, a plasma vWF decrease after parathyroidectomy might reflect a specific mechanism of its endothelial calcium- and/or PTH-stimulated secretion in some PHPT patients without risk factors. Whether a vWF reduction after parathyroidectomy may be used as a biochemical index for improved endothelial function in PHPT patients without risk factors has yet to be demonstrated in larger studies.
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PMID:Biochemical markers of endothelial activation in primary hyperparathyroidism. 1652 14

The calcium-sensing receptor has a key role in calcium homeostasis, it is involved in the regulation of the serum calcium level within minutes via the secretion and action of parathyroid and the excretion of calcium in the kidney in a negative feedback manner. Mutations of the calcium sensing receptor gene leads to inactivating and activating mutations resulting in diseases with hypercalcaemia and hypocalcaemia. The loss of function mutations are associated with familial benign hypocalciuric hypercalcaemia (FHH), an autosomal dominant disease characterised by lifelong mild hypercalcaemia, low urinary calcium excretion, and inappropriate high parathyroid hormone levels, sometimes difficult to distinguish from mild asymptomatic primary hyperparathyroidism. Patients with FHH did not profit from parathyroidectomy, a calcium lowering therapy is not necessary. The gain of function mutations of the calcium-sensing receptor are associated with autosomal dominant hypocalcaemia (ADH), a disease characterised by a generally asymptomatic hypocalcaemia, inappropriately high urinary calcium excretion and normal PTH levels. A therapy to raise the serum calcium concentration has to be done carefully and is only indicated in symptomatic patients, because of enhancement of hypercalciuria with the risk of nephrocalcinosis and nephrolithiasis. Molecular genetic analysis of the calcium sensing receptor gene facilitates the sometimes difficult diagnosis. The development of compounds modulating the calcium sensing receptor function and thereby the section of PTH may become an important role in treatment of diseases of calcium metabolism.
Exp Clin Endocrinol Diabetes 2006 Sep
PMID:The role of the extracellular calcium-sensing receptor in health and disease. 1703 19

Cardiovascular disease (CVD) is a major cause of death in peritoneal dialysed patients (PD-pts). Coronary artery calcification (CAC) is likely to affect the development of CVD. Purpose of our study was to evaluate coronary artery calcification and risk factors of this calcification in PD-pts. We studied 62 patients (38 F, 24 M) undergoing peritoneal dialysis (PD). Coronary calcification was examined by ECG-gated multidetector CT (Light Speed Ultra) using Agatson (AG) and volumetric (V) methods. Patients were divided into 3 groups depending on mean value of estimated CAC: group A-no calcification, group B-CAC maximal value 400 mm3, group C-CAC value more than 400 mm3. As risk factors of CAC were evaluated: patients age, sex, dialysis duration, serum concentration of Ca, P, homocysteine CRP and fibrinogen, as well as, CaxP product, intact PTH; presence of diabetes or hypertension. Coronary artery calcification was detected in 68% of patients. In the whole observed population positive correlation between CAC determined by AG and V methods and CRP (r = 0.36, p < 0.05) as well as patients age (r = 0.5, p < 0.01) was observed. There was also positive correlation between CAC and fibrinogen concentration (AG CAC r = 0.58, p < 0.05; V CAC r = 0.72, p < 0.05). When compared group C with the groups A and B cardiovascular complications were in this group more frequent than in the last two: 4 patients from group C died because of cardiovascular complications.
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PMID:[Analysis of some risk factors of coronary artery calcification in peritoneal dialysis patients]. 1707 89

Diabetic osteopenia causes an increase in bone fracture and a delay in healing of fractures, and affects the quality of life. However, the mechanisms responsible for the disease have not been clearly identified. Oxidative stress may be a potential candidate for the pathogenesis, since it is increased under diabetic conditions and is known to induce cellular dysfunction in a wide variety of cell types. Although in vitro studies have shown that oxidative stress inhibits osteoblastic differentiation and induces osteoblast insults and apoptosis, the relationship between diabetic osteopenia and oxidative stress remains unclear. To explore these issues, analysis of a mouse model that represents the diabetic osteopenia as seen in patients with diabetes is necessary. However, there are few reports of such a model. Therefore, we focused on the streptozotocin (STZ)-induced diabetic mouse, one of the most common animal models of type 1 diabetes. Eight-week-old male C57BL/6 mice were randomly assigned to the following three groups: 1) control group, 2) diabetic group, and 3) insulin-treated diabetic group. After 12 weeks of STZ treatment, the physical properties of the femora, and the static and dynamic parameters of bone histomorphometry of the tibiae from STZ-induced diabetic mice (STZ-mice) were assessed, and oxidative stress in the whole body and bone of the mice was evaluated. Renal function was comparable in all three groups at the end of the experimental period. In addition, no significant difference in serum PTH, Ca, and P was found among the three groups. In contrast, radiological analysis demonstrated a significant decrease in trabecular bone volume, and histomorphometric analyses confirmed that parameters for both bone formation (OV/BV, OS/BS, and BFR/BS) and bone resorption (ES/BS and Oc.S/BS) were also significantly lower in STZ-mice. In addition, urinary excretion of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, was elevated in STZ-mice. Further immunohistological studies showed intensified immunostaining of an oxidative stress marker in bone tissue including the osteoblasts of diabetic mice. Here, we demonstrated that STZ-mice exhibit low-turnover osteopenia associated with increased oxidative stress.
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PMID:Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: a possible role of oxidative stress. 1725 Oct 74


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