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Query: UMLS:C0011849 (diabetes)
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An elderly man with diabetes mellitus and end-stage renal disease managed with continuous ambulatory peritoneal dialysis (CAPD) was hospitalized with peripheral vascular insufficiency; he developed hypercalcemia and became mentally obtunded. Lowering dialysate Ca from 3.5 mEq/L to 2.5 mEq/L, stopping calcium acetate, and ultimately hemodialysis with calcium-free dialysate did not lead to reversal of the hypercalcemia or improvement of his symptoms. The intact parathyroid hormone PTH level was 187 pg/mL, a value rarely associated with significant osteitis fibrosa. A search for other causes of hypercalcemia was unrevealing, and a iliac crest bone biopsy was done. The latter showed osteitis fibrosa, and the patient underwent parathyroidectomy. The hypercalcemia reversed quickly, and his mental symptoms slowly improved. The discussion reviews the probable causes of hypercalcemia in diabetic patient undergoing CAPD with 3.5 mEq/L dialysate calcium and using calcium-containing phosphate binders, with hyperparathyroidism certainly not the usual cause. The reason for the occurrence of significant hyperparathyroidism in the face of only modest elevation of PTH is considered. The value of bone biopsy in resolution of this problem is apparent.
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PMID:Symptomatic hypercalcemia in a diabetic patient undergoing continuous ambulatory peritoneal dialysis: value of bone biopsy in the diagnosis and management. 748 41

Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis. 752 7

It is known that osteopenia is frequently associated with diabetes mellitus. Although its mechanism is not well understood, impaired bone formation due to an osteoblast deficit seems to be a major factor as reflected by a fall in serum levels of osteocalcin and by the findings of low bone formation with bone histomorphometry. In the present study, we studied the effect of high glucose conditions on osteoblast by examining the responsiveness of human osteosarcoma (MG-63) cells to human parathyroid hormone 1-34 [hPTH-(1-34)]. MG-63 cells were cultured either with 5.5 mM glucose (normal glucose), 55.0 mM glucose (high glucose) or 5.5 mM glucose plus 49.5 mM mannitol (high mannitol) condition for 7 days. Both an increase in cAMP levels and an immediate increase in [Ca2+]i, induced by hPTH(1-34), were significantly lower in high glucose-treated cells than in those treated with normal glucose or high mannitol. Basal cAMP levels in the cells after a 7-day culture in high glucose conditions were significantly higher than in those in the other two groups. We concluded that high glucose specifically impaired the response to hPTH(1-34). This impairment seemed to arise from an increase in intracellular cAMP levels, which is reported to induce downregulation of PTH receptors.
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PMID:Impaired response of human osteosarcoma (MG-63) cells to human parathyroid hormone induced by sustained exposure to high glucose. 756 50

A 50-year-old man was admitted to our hospital for the evaluation of hypocalcemia and the treatment of diabetes mellitus. Seven months before admission, he sometimes felt thirst and polyuria, and 4 months before admission, he went to a doctor to check his blood glucose and was diagnosed as having diabetes mellitus which had suddenly developed. At that time he was treated with sulfonylurea, but his diabetic control was very poor. At the time of admission to our hospital, the patient's serum calcium (Ca) level was 5.7 mg/dl, phosphorus (P) 5.0 mg/dl, and fasting blood glucose 308 mg/dl, but urinary ketone bodies were not detected. High sensitive assay of parathyroid hormone (HS-PTH), intact PTH and C-terminus PTH concentrations were under the level of detection. TSH level was slightly high (6.1 mu U/ml) with positive antimicrosomal and antithyroglobulin antibodies but thyroid hormone levels were within normal limits. TRH test showed over-response of TSH. Based on Ellsworth-Howard test, we made the diagnosis of idiopathic hypoparathyroidism associated with primary hypothyroidism and diabetes mellitus. He was treated with insulin twice a day and reached good control, and he was also administered 1 alpha-OH-D3 and calcium lactate resulting in an increase of serum Ca level after 2 weeks. These findings suggest that this case may be a polyglandular autoimmune (PGA) syndrome type 1 reported by Neufeld, which is very rare in Japan. The type of diabetes mellitus of this case is controversial. It is, however, necessary to pay attention to the decrease of the patient's insulin-secreting activity because autoimmune disorders are accompanied by this case.
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PMID:[A case of idiopathic hypoparathyroidism associated with primary hypothyroidism and diabetes mellitus]. 795 10

Osteocalcin and PTH serum levels were measured in 41 insulin-dependent diabetic pregnant women through the three trimesters of pregnancy with a total of 106 determinations of osteocalcin and 137 of PTH. In parallel we quantified these parameters in 90 normal pregnant women throughout the three trimesters of pregnancy. In addition calcitriol, osteocalcin and PTH levels were quantified at delivery in 16 diabetic pregnant women and 16 normal pregnant women at delivery, in cord serum and in the infants during the first days of life. Non-pregnant women (n = 48) were the control group. In normal pregnant women PTH levels increased during the third trimester and total calcitriol increased at delivery. Osteocalcin levels decreased in the second trimester but returned to normal values during the third trimester of pregnancy. Diabetic pregnant women showed constant PTH levels throughout pregnancy. At delivery in diabetic pregnant women, total calcitriol levels increased to a smaller extent than in normal pregnant women. Osteocalcin concentrations in the second and third trimester of pregnancy were lower than in the non-pregnant group. Infants of diabetic mothers showed lower PTH and osteocalcin concentrations than infants of normal pregnant women, whereas their calcitriol levels were similar. These data indicate that diabetes decreases bone turnover during pregnancy in the mother and during the perinatal period in their offspring.
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PMID:Serum osteocalcin concentrations in diabetic pregnant women and their newborns. 795 11

To explore the pathogenesis of diabetes associated osteopenia, we characterized the osteopenia in streptozotocin (STZ)-diabetic rats pharmacologically and biochemically. The femur metaphyseal bone mineral density measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reached statistical significance from 2 weeks after treatment with STZ. Closely similar bone loss was obtained in ovariectomized (Ovx) and vitamin D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844 (a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but not in the D(-) rats, while 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) significantly attenuated the osteopenia in the STZ and D(-) rats in a dose of 0.1 microgram/kg/day, and that in the Ovx rats in 1 microgram/kg/day. The latter dose of 1 alpha-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), the most active metabolite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76% that of control in the STZ and D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) rats were comparable with those in controls, but serum calcitonin levels were reduced to 60 and 66% of control in the STZ and Ovx rats, respectively. Serum osteocalcin levels also decreased in the STZ rats compared to control. It is thus speculated that the predominance of bone resorption over bone formation and the reduction of 1 alpha, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.
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PMID:Possible involvement of vitamin D3-deficiency and relatively enhanced bone resorption in the development of bone loss in streptozotocin-induced diabetic rats. 802 47

Cyclosporin A (CsA) is widely used in diabetic transplant patients and early type I diabetes mellitus. Diabetes produces a low-turnover osteopenia, and CsA conversely induces high-turnover osteopenia in rats. We investigated whether CsA would exacerbate diabetic osteopenia. Four groups of 10-week-old male Sprague-Dawley rats (n = 11/group) were studied: On day -6, groups A and C received saline and groups B and D received intravenous streptozotocin (55 mg/kg) to induce diabetes. From day 0, groups A and B received CsA vehicle and C and D received CsA (15 mg/kg) by daily gavage. Rats were bled on days -6, 0, 11, and 22 for serum bone gla protein (BGP), 1,25-(OH)2D, PTH, blood ionized Ca, and blood glucose determinations. Double tetracycline labeling was performed on days 9 and 20 for bone histomorphometry. After sacrifice on day 22, histomorphometric analysis was performed. Serum BGP, 1,25-(OH)2D, and PTH levels were significantly decreased in the diabetic alone (B) and diabetic plus CsA (D) groups and significantly increased in the CsA alone (group C). CsA alone (group C) induced cancellous bone loss by stimulated bone resorption. Cancellous bone loss in the diabetic alone rats (group B) was caused primarily by inhibited bone formation. No differences were found in cancellous bone mass, formation, or resorption parameters between diabetic alone (group B) and CsA-treated diabetic rats (group D). Neither CsA alone (group C) nor diabetic alone (group B) nor their combination affected cortical bone mass. CsA alone (group C) stimulated periosteal bone formation and endocortical bone resorption and inhibited endocortical formation, and diabetic alone (group B) inhibited both periosteal and endocortical bone formation. No parameters of tibial diaphyses in CsA-treated diabetic rats (group D) were different from diabetic alone. Thus the addition of CSA to the diabetic treated rats (group D) could not stimulate remodeling and appeared not to worsen significantly some of the alterations in bone formation and resorption. Possible explanations for this may be that CsA in vivo requires adequate levels of PTH, 1,25-(OH)2D, insulin, and perhaps growth factors to stimulate remodeling. The use of CsA in type I diabetic patients or in organ transplant recipients who remain diabetic after transplantation may in the short term not aggravate existing osteopenia based on these findings.
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PMID:Effect of cyclosporin A on bone mineral metabolism in experimental diabetes mellitus in the rat. 803 Apr 44

To clarify the role of serum vitamin D and bone remodeling markers in postmenopausal diabetic azotemics, we designed a study involving 3 different postmenopausal patient groups. Group I consisted of 20 diabetic women with renal insufficiency who were not yet on dialysis therapy. Group II consisted of 15 age-matched nondiabetic women with comparable degrees of renal insufficiency. Group III consisted of 20 age-matched women with normal renal function. We investigated the overnight fasting serum 25 (OH) vit-D, 1,25(OH)2 vit-D3, osteocalcin (OC), bone isoenzyme of alkaline phosphatase (ALK-PB) and intact parathyroid hormone (I-PTH) levels in these cases. The serum I-PTH and OC levels were statistically significantly higher, whereas 1,25(OH)2vit-D3 were significantly lower in Group I and Group II patients than in Group III patients. We found no significant correlation between elevation of I-PTH and reduced 1,25(OH)2 vit-D3 levels in Group I and Group II patients. I-PTH levels correlated positively with OC in Group I and Group II patients. There was no significant difference in serum 25(OH) vit-D among these 3 groups of patients. We conclude that (1) serum OC level may serve as a good parameter in evaluating secondary hyperparathyroidism in postmenopausal azotemics with or without diabetes, (2) even in the presence of menopause, renal failure per se is the main factor in determining serum 1,25(OH)2 vit-D3 levels in diabetic azotemics.
Diabetes Res 1993
PMID:Serum osteocalcin and vitamin D in postmenopausal diabetic azotemics. 807 46

Recent studies have revealed that altered mineral and vitamin D metabolism is observed in diabetic patients with the complication of osteopenia. In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) on calcium homeostasis in diabetes, we have measured the serum level and urinary excretion of PTHrP as well as other serum calcium-regulating hormones in 106 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 43 control subjects. The serum concentration of intact PTH was 2.34 +/- 0.13 (mean +/- SEM) pmol/l in NIDDM patients, which is significantly lower than the value of 3.11 +/- 0.14 pmol/l in the controls (p < 0.01). Both serum calcium and calcitonin, however, were not statistically different from controls. On the other hand, circulating PTHrP in NIDDM was 40.1 +/- 1.4 pmol/l, which is significantly elevated when compared to 27.3 +/- 1.3 pmol/l in the controls (p < 0.01). Moreover, urinary excretion of PTHrP also was significantly higher in NIDDM (p < 0.01). In the present study, the circulating calcium level was well preserved in NIDDM patients, although the PTH levels were shown to be decreased. The elevated serum PTHrP might, therefore, have a physiologically compensatory role on the calcium regulatory systems in NIDDM. Furthermore, this elevation is most likely due to the excess production of this peptide and not to the decrease in urinary excretion.
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PMID:Possible compensatory role of parathyroid hormone-related peptide on maintenance of calcium homeostasis in patients with non-insulin-dependent diabetes mellitus. 810 85

We evaluated 259 dialysis patients using serum parathyroid hormone (PTH, IRMA; normal range 1 to 5.5 pM or 10 to 55 pg/ml), the deferoxamine infusion test and iliac crest bone biopsy to determine the various forms of renal osteodystrophy and their risk factors. Although half of the biopsied patients had low turnover osteodystrophy, evidence of aluminum toxicity was present in only 1/3 of them. Additional risk factors for this bone lesion included treatment with peritoneal dialysis, ingestion of calcium carbonate, diabetes mellitus and advanced age. The PTH levels in patients with the aplastic lesion were significantly lower than in patients with normal or high bone turnover lesions [7.7 +/- 6.1 vs. 36.9 +/- 3.2 pM (77 +/- 61 vs. 369 +/- 32 pg/ml), P < 0.0001]. Aside from hypercalcemia, these patients were relatively asymptomatic. In a second study, 10 patients on peritoneal dialysis with the aplastic lesion had their dialysate calcium lowered from 1.62 to 1.0 mM. This resulted in a significant increase in PTH levels, from [3.7 +/- 0.8 to 10.6 +/- 1.9 pM (37 +/- 8 to 106 +/- 19 pg/ml), P < 0.001] which persisted over the nine-month observation period. In conclusion, the aplastic lesion is the most common form of renal osteodystrophy, with aluminum intoxication implicated in only 1/3 of the cases. In the remainder, factors identified include therapy with peritoneal dialysis using supraphysiological dialysate calcium, oral CaCO3 intake and diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aplastic osteodystrophy without aluminum: the role of "suppressed" parathyroid function. 825 62


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