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)

Osteoporosis, a recognized complication of insulin-dependent diabetes mellitus (IDDM), may be related to this complex metabolic disorder; moreover, some data emphasize an altered vitamin D metabolism or parathyroid hormone secretion. Mineral homeostasis was studied in 29 children with IDDM (18 males, 11 females; 2.6-18.0 years). In 17 patients a stimulatory test (low-calcium diet) was performed for PTH and 1.25(OH)2D. Bone mineral content (BMC) and BMC/BW were lower in respect to our normal values; bone mineral loss was directly related to HbA1c levels and insulin requirements. A significant decrease of ionized calcium (p less than 0.001) and magnesium (p less than 0.001) was found; intact PTH values were in the low normal range but decreased for the ionized calcium values. 1.25(OH)2D levels were not significantly different from normal levels. 1.25(OH)2D and intact PTH did not rise during stimulatory test. The lack of 1.25(OH)2D and intact PTH increase after the stimulatory test may be due to the parathyroid gland's hyporesponsiveness related to hypomagnesemia which impaired PTH release and/or PTH action. Our data confirm an involvement of 1.25(OH)2D and PTH regulation in diabetic osteoporosis.
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PMID:Bone demineralization and impaired mineral metabolism in insulin-dependent diabetes mellitus. A possible role of magnesium deficiency. 278 12

Because a series of reports suggests the existence of altered bone and mineral metabolism in diabetes mellitus, we studied 106 diabetic subjects (42 insulin-dependent (IDD) and 64 noninsulin dependent (NIDD] to determine whether a difference in bone turnover (evaluated by serum osteocalcin (OC] could be found in comparison with normal controls. OC levels in diabetic subjects were lower than the age- and sex-specific predicted values. The reduction was especially evident in male and female NIDD (Z-score: - 1.12 +/- 0.92, t = 8.4, P less than 0.001 and -0.84 +/- 0.86, t = 4.0, P less than 0.01, respectively) and male IDD (Z-score: - 0.90 +/- 0.86, t = 4.5, P less than 0.01). The mean Z-score for female IDD, albeit negative (-0.31 +/- 0.79; t = 1.6; 0.2 greater than P greater than 0.1), was not significantly different from normal. Total serum calcium (Ca) and calcitonin (CT) showed an opposite pattern, being higher in all the diabetic subgroups (with the exception of Ca in female IDD), whereas parathyroid hormone (PTH) was lower than expected in each diabetic subset. By multiple regression analysis, the reduction of OC was related to PTH and CT levels and to the type of treatment. Subjects controlled with diet showed differences of greater magnitude from the expected normal values than those treated with oral hypoglycemic agents or insulin (Z-score: -1.28 +/- 1.05 vs. -0.85 +/- 0.90 and -0.63 +/- 0.97, respectively; P = 0.05). However, the variance explained by these three factors was small, suggesting that other variables (possibly 1 alpha,25(OH)2D) exerted important influences on OC levels.
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PMID:Osteocalcin levels in diabetic subjects. 224 99

The responsiveness of parathyroid cells in insulin deficient and short-term diabetic rats was investigated by morphometric analysis. Insulin deficiency was produced by intravenous injection of D-mannoheptulose and short-term (7 days) diabetes mellitus by intraperitoneal application of streptozotocin. Parathyroid glands were stimulated for parathyroid hormone secretion by decreasing the serum calcium concentration through intravenous infusion of EGTA. Parathyroid cells of controls, insulin deficient, and short-term diabetic rats responded to reduced serum calcium by a 45% increase of the cell surface area. This increase is assumed to be the result of the membrane-bound transport of parathyroid hormone from the Golgi complex and secretory granules to the plasma membrane and subsequent exocytic release of parathyroid hormone induced by the low serum calcium concentration. Therefore, the unimpaired increase in the cell surface area of parathyroid cells in insulin deficient and short-term diabetic rats indicates that insulin does not modulate the release of parathyroid hormone. It is also considered likely that synthesis of parathyroid hormone is not suppressed in short-term diabetes but that fat metabolism is disturbed leading to accumulation of lipid vacuoles.
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PMID:Unimpaired membrane dynamics in parathyroid cells in insulin deficient rats. 289 31

To assess the affect of mild diabetes on calcium metabolism in an animal model, we evaluated calcium homeostasis before pregnancy and during gestation and lactation in non-insulindependent (NIDD) diabetic rat mothers and their neonates (NeoDM). Plasma glucose, calcium (Ca), magnesium (Mg), phosphate (Pi), and immunoreactive parathyroid hormone (iPTH) were measured in the NIDD rats and controls before pregnancy, during the first, second, and third gestational week, and during lactation 12, 24, 48 and 72 h postpartum. The same measurements were performed on NeoDM and controls 12, 24, 48, and 72 h after birth. In the mothers, plasma calcitonin was assayed before pregnancy and at 72 h postpartum. Higher plasma glucose values before pregnancy (216 +/- 9 mg/dl vs 126 +/- 4) and during the second (105 +/- 5 vs 73 +/- 6) and third (114 +/- 8 vs 91 +/- 3) gestational week were observed in diabetic mothers when compared to controls. Glucose values decreased during the second and third gestational week in both groups compared to pregestational values. Plasma Ca, Mg, and Pi were similar in both groups during gestation and lactation except for the third gestational week when plasma Mg was lower in the diabetic mothers (P less than 0.05). Plasma iPTH rose to similar values in both groups during pregnancy. During lactation, plasma iPTH levels were higher and plasma calcitonin levels were lower compared to controls (P less than .05, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mineral homeostasis in neonates of streptozotocin-induced noninsulin-dependent diabetic rats and in their mothers during pregnancy and lactation. 295 60

In short-term experiments, male Wistar rats were made diabetic for 10 days with a single injection of streptozotocin (65 mg/kg body weight). One group of diabetic rats was treated with insulin for 3 days prior to sacrifice. In long-term experiments, vitamin D replete or vitamin D depleted rats were made diabetic for 6 weeks. Criteria for diabetes were loss of weight, glycosuria (Tes-Tape), and hyperglycemia. In long-term diabetic rats the activity of renal mitochondrial 25-hydroxyvitamin D3 (25-(OH)D3) 1 alpha-hydroxylase was significantly decreased and that of 25-(OH)D3 24-hydroxylase increased. However, the parathyroid hormone (PTH) sensitive renal adenylate cyclase activity of diabetic rats was not different from that of the nondiabetic rats in either the vitamin D replete group or the vitamin D depleted group. On the other hand, the PTH-sensitive renal adenylate cyclase activity was significantly higher in short-term diabetic rats than in control and insulin-treated rats. These differences were observed at doses of 10(-8) to 10(-5) M of PTH. This study has demonstrated for the first time that there are differences in the PTH-sensitive adenylate cyclase response between long-term and short-term diabetic rats. The hypersensitivity to PTH of the renal adenylate cyclase observed in short-term diabetic rats probably represents a response to insulin deficiency during the early development of diabetes mellitus in the rats.
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PMID:Effect of long-term and short-term diabetes on the parathyroid hormone sensitive rat renal adenylate cyclase: correlation with vitamin D metabolism. 307 95

Previous studies of patients with end-stage renal disease (ESRD) indicate that the prevalence of goiter varies from 0 to 58% while that of hypothyroidism ranges from 0 to 9.5%. In addition, altered serum thyroid hormone levels are present in euthyroid patients with ESRD and may be related to nonthyroidal disorders including malnutrition. To examine these issues further, 306 patients with ESRD were compared to 139 hospitalized patients without renal disease (control population). Goiter was present in 43% with ESRD compared to 6.7% of controls (P less than 0.001). Goiter frequency was greater (49.6%, P = 0.047) and serum parathyroid hormone levels higher (mean: 238.6 microlitersEq/ml, P less than 0.001; normal: less than 15 microlitersEq/ml) in 115 patients dialyzed for longer than 1 year than in 191 dialyzed for less than 1 year or not at all (38.7%, and 61.5 microlitersEq/ml, respectively). In addition, goiter was more common in females (50.0%) than in males (35.1%, P = 0.008) with ESRD. No significant relationships were observed between goiter frequency and age, race, diabetes mellitus, or elevated antimicrosomal antibody titers. The prevalence of primary hypothyroidism was higher in ESRD (2.6%) than in 2122 in- and out-patients (1.1%) (P = 0.024). Compared to the total group of ESRD patients, the hypothyroid patients were predominantly female (88% vs. 50%) and had a higher frequency of positive antimicrosomal antibody titers (50% vs. 6.7%, P = 0.029). The frequency of hyperthyroidism was not significantly different, being 1.0% in ESRD compared to 0.3% in the general population (P = 0.057). There was a higher frequency of reduced free T4 index values in the 287 euthyroid patients with ESRD (12.9%) than in controls (3.6%) (P = 0.002). Similarly, free T3 index values were reduced below 100 in 65.5% with ESRD compared to 33.8% of controls (P less than 0.001). In addition, serum albumin levels were lower in euthyroid patients with ESRD (3.5 g/dl, P less than 0.001) than in controls (3.8 g/dl). Serum T3 levels correlated directly with both serum albumin (r = 0.57, P less than 0.001) and transferrin (r = 0.54, P less than 0.001) levels in ESRD as well as in controls (r = 0.74, P less than 0.001, and r = 0.69, P less than 0.001, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The thyroid in end-stage renal disease. 325 81

Recent studies indicate that serum levels of osteocalcin, a 49-aminoacid bone matrix protein, are a biochemical marker of bone formation. In order to study bone metabolism in diabetes mellitus, in 28 patients with Type 1 (insulin-dependent) diabetes mellitus, in 38 patients with Type 2 (non-insulin-dependent) diabetes mellitus and two control groups, matched for Type 1 and Type 2 diabetic patients, respectively, serum levels of osteocalcin, parathyroid hormone and 25 hydroxy vitamin D were measured by radioimmunoassay. Whereas in Type 1 diabetic patients and control subjects serum levels of osteocalcin and 25 hydroxy vitamin D were not statistically different, serum osteocalcin and 25 hydroxy vitamin D levels were significantly decreased in Type 2 diabetic patients when compared with corresponding control subjects (p less than 0.03 and p less than 0.001, respectively). Independent of the type of diabetes, serum parathyroid hormone levels were comparable in diabetic patients and matched control subjects. Serum osteocalcin levels were significantly lower in Type 1 diabetic patients with retinopathy and/or proteinuria than in Type 1 diabetic patients without microangiopathy (p less than 0.05). Whereas serum parathyroid hormone levels in Type 2 diabetic patients with retinopathy and/or proteinuria were significantly increased (p less than 0.02), 25 hydroxy vitamin D levels were decreased (p less than 0.02) when compared with Type 2 diabetic patients without microangiopathy. Our data give evidence of a vitamin D deficiency and a decreased bone formation in patients with Type 2 diabetes mellitus. In Type 1 diabetes mellitus bone formation as reflected by serum osteocalcin levels is influenced by the presence or absence of microangiopathic complications.
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PMID:Serum osteocalcin levels in diabetes mellitus: analysis of the type of diabetes and microvascular complications. 326 86

Bone disease related to aluminum toxicity (aluminum-related bone disease) presents with variable clinical and biochemical findings in patients with renal failure. Bone pain and muscle weakness are common, although afflicted patients can be asymptomatic. Bone pain can be generalized or localized to the hips, back, feet, or ankles; proximal muscle weakness is common. Most cases in the United States arise from the ingestion of aluminum-containing gels by patients on long-term dialysis treatment. Patients at increased risk for developing aluminum-related bone disease include those with earlier parathyroidectomy, failed renal transplant, previous bilateral nephrectomy, and diabetes mellitus. Biochemical features that are common with aluminum-related bone disease include plasma aluminum levels greater than 100 to 150 micrograms/L, serum parathyroid hormone (PTH) levels equal to or lower than those in dialysis patients without bone disease, and normal or slightly elevated serum calcium levels. Plasma alkaline phosphatase levels are often elevated. In our experience, microcytic anemia has been uncommon. An increase in plasma aluminum levels greater than 200 micrograms/L 24 to 48 hours after the infusion of the chelating agent deferoxamine (DFO) correlates with an increased bone aluminum content, and an increment greater than 400 micrograms/L suggests marked aluminum accumulation. Radiographs are usually nonspecific. When results from indirect diagnostic procedures are equivocal, a bone biopsy is necessary. After a diagnosis of aluminum-related bone disease is established, therapy with DFO may be useful. DFO increases both the total plasma aluminum level and its ultrafilterable fraction. After an infusion of DFO, the removal of aluminum increases from 50 to 300 micrograms to 4 to 8 mg per dialysis session. Aluminum removal is similar during continuous ambulatory peritoneal dialysis after either intravenous (IV) or intraperitoneal (IP) administration of DFO. Usually, 2 to 4 g of DFO is administered once weekly, but the optimal dose and duration of therapy have not been determined. Symptoms usually improve after 4 to 12 weeks, and bone biopsies show improvement after treatment for 6 to 12 months. Further experience with DFO is needed, both to identify the optimal dosage and to clarify the risks of long-term therapy in patients with renal failure.
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PMID:Diagnosis of aluminum-related bone disease and treatment of aluminum toxicity with deferoxamine. 329 88

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP-stimulated endoproteases appear to catalyse the rate-limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin-1 and inhibited by Ep-475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline proteinase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo-proteinase. Plasma alpha 2-macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine. In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proteinases in catabolism and malnutrition. 331

Bone biopsies and plasma parathyroid hormone (PTH) from 27 diabetic dialysis patients were compared to biopsies and PTH levels from matched patients without diabetes to determine if PTH has a role in preserving bone mass in diabetic renal osteodystrophy. Significantly lower values were present in the diabetic group for mineralized bone area (p less than 0.003), osteoblastic osteoid (p less than 0.01), resorptive surface (p less than 0.001), fibrosis (p less than 0.005), bone apposition rate (p less than 0.01), bone formation rate (BMU level) (p less than 0.04), and plasma PTH (p less than 0.05). Bone-surface aluminum was higher in the diabetic group (44 +/- 5% vs. 20 +/- 5%, p less than 0.005). Linear regression analysis revealed significant positive correlations of mineralized bone area with time on dialysis, bone formation rate, bone resorption, and PTH only in the group without diabetes. While both groups had significant positive correlations of PTH with osteoblastic osteoid and bone resorption, only in the nondiabetic group was there a positive correlation of PTH with bone apposition and bone formation rate (BMU level), observations suggesting that the lower bone formation in the diabetic patients may have arisen in part from a failure of PTH to promote bone mineralization. We conclude that relatively low PTH levels and high bone aluminum in diabetic patients with chronic renal failure may be responsible in part for low bone mass when compared to uremic patients without diabetes.
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PMID:Bone histomorphometry of renal osteodystrophy in diabetic patients. 345 34


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