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

Reduced bone mineral density (BMD), termed diabetic osteopenia, has been reported in patients with insulin-dependent (Type 1) diabetes mellitus (IDDM). To examine BMD in long-term IDDM patients with normal kidney function, but with different degrees of urinary albumin excretion rate (UAER), compared to that of patients with elevated plasma creatinine, 36 IDDM male patients (mean duration 27 years) were subdivided according to UAER (<30, 30-300, >300, >300 mg 24 h(-1) and plasma creatinine 0.120-0.350 mmol l(-1)) and 15 controls were recruited. BMD was measured by dual energy X-ray absorptiometry and UAER by enzyme linked immunosorbent assay. BMD was normal in IDDM patients with normal UAER and reduced in the femoral neck, the trochanter major, and the Wards triangle in patients with increased UAER (p < 0.01, p < 0.05, p < 0.02). BMD correlated to creatinine clearance in both cortical and cancellous bone sites (p < 0.001, p < 0.0001), and inversely to the levels of plasma PTH (p < 0.0005). We conclude that BMD is normal in long-term IDDM male patients with normal kidney function and normal UAER and reduced in patients with increased UAER. Diabetic osteopenia seems to be a progressive phenomenon related to diabetic nephropathy and associated with the decrease in creatinine clearance and with the resulting rise in plasma PTH.
 ...
PMID:Microalbuminuria as an early indicator of osteopenia in male insulin-dependent diabetic patients. 945 31

We report a sporadic case of Albright's hereditary osteodystrophy (AHO)-like syndrome with several endocrinopathies. A 37-yr-old woman had an appearance of AHO but did not have renal PTH resistance. Her case was complicated by non-insulin-dependent diabetes mellitus with severe insulin resistance, central diabetes insipidus, and hyposecretion of GH. Most patients with AHO are found in a family of pseudohypoparathyroidism type-Ia and have a heterozygous mutation that inactivates the alpha-subunit of Gs (Gs alpha), the stimulatory regulator of adenylyl cyclase. Some sporadic cases occur in which patients with phenotype similar to AHO have a deletion of chromosome 2q37. However, in this patient, both the Gs alpha gene structure and the biological activity were normal. In addition, chromosome analysis revealed a normal pattern with no visible deletion of chromosome 2q37. Our findings suggest that one or more other factors may be involved in the pathogenesis of AHO-related disease.
 ...
PMID:A case of Albright's hereditary osteodystrophy-like syndrome complicated by several endocrinopathies: normal Gs alpha gene and chromosome 2q37. 958 56

The interaction of cells with the surrounding extracellular matrix (ECM) or basement membrane (BM) brings about profound changes in cellular biological responses, such as cell differentiation, proliferation, and gene expression. We studied the effect of ECM on PTH receptor binding and on biological responses mediated by PTH, in two cell preparations: 1) the proximal tubular OK opossum kidney cell line; and 2) MC3T3-E1 cells, a clonal line of nontransformed murine osteoblasts. Cells were plated on either plastic surfaces or on tissue culture dishes coated with specific ECM components. In both cell types plated on collagen-type IV (Col-IV), PTH receptor binding, on day 4 of culture, was markedly diminished, when compared with cells on plastic (approximately 45% inhibition, P < 0.01). In addition, Col-IV dose dependently inhibited cAMP generation stimulated by PTH (P < 0.001 vs. plastic), whereas cAMP generation by PGE2, cholera toxin, and forskolin was not altered. In Northern blot analysis, a PTH/PTH-related-protein receptor messenger RNA transcript was detected in both the kidney and bone cells. However, only OK cells manifested a decreased abundance of receptor messenger RNA when plated on Col-IV, compared with plastic. The physiological significance of inhibited cAMP production by Col-IV was evaluated by measuring the influence of different matrices on the activity of Na+/H+ exchanger (NHE) in OK cells and cell mitogenic activity in MC3T3-E1 cells (both responses are negatively modulated by cAMP). OK cells plated on Col-IV showed 70% inhibition of NHE, compared with cells plated on plastic (P < 0.01). PTH inhibits NHE activity in cells on plastic but stimulates exchanger activity by 40% in cells plated on Col-IV. In MC3T3-E1 cells grown on plastic, PTH exerts a dose-dependent antiproliferative effect, which is mediated by cAMP. This effect is mitigated when cells are grown on Col-IV (40-50% less antiproliferative effect). In summary, Col-IV, a maj or BM constituent, has a profound inhibitory effect on PTH binding and PTH-mediated biological responses in both kidney tubular cells and osteoblasts. Altered cellular function by Col-IV may be of physiological relevance in states associated with altered composition of BM or expansion of ECM (e.g. diabetes mellitus and interstitial fibrosis).
 ...
PMID:The effect of cell-matrix interaction on parathyroid hormone (PTH) receptor binding and PTH responsiveness in proximal renal tubular cells and osteoblast-like cells. 964 78

We present 2 cases of progressively severe Kearns-Sayre syndrome (KSS) with multisystemic affectation and atypical endocrine and cutaneous features, a 16-year-old patient (case 1) and a 5-year-old patient (case 2). Endocrine studies showed high glucose and glycohemoglobin concentrations with normal pancreatic reserve and low values of ACTH, cortisol, LH and FSH in case 1. Normal ACTH values with low concentrations of cortisol and PTH were observed in case 2. Southern blot analysis and PCR amplification revealed the presence of a deletion of approximately 6.7 kb in the mitochondrial DNA of both patients. Endocrinological studies suggest that adrenal insufficiency may be an additional feature of KSS that worsens the clinical evolution of the patients. In spite of a normal pancreatic reserve, insulin therapy should be considered in patients with diabetes mellitus of mitochondrial origin.
 ...
PMID:Multiple endocrine involvement in two pediatric patients with Kearns-Sayre syndrome. 970 4

Several factors have been identified as important in the pathogenesis of secondary hyperparathyroidism in end-stage renal disease, including serum calcium, phosphorus, and calcitriol. To examine the independent effects of key factors, we prospectively studied 52 new hemodialysis patients with mild secondary hyperparathyroidism (PTH, 110-670 pg/mL) treated with a standardized regimen of calcium supplements, phosphorus binders, and no vitamin D derivatives. We used simple and multivariable linear regression analysis to examine the relationship between changes in PTH (deltaPTH) levels observed over a 4-week period and various biochemical and demographic variables. By simple linear regression we found that changes in serum phosphorus (r2 = 0.31; beta = 41.6; P = 0.0001), initial phosphorus concentration (r2 = 0.15; beta = 33.4; P = 0.005), initial PTH level (r2 = 0.29; beta = 0.58; P = 0.0001), changes in serum calcium (r2 = 0.12; beta = -74.0; P = 0.01), and gender (r2 = 0.07; beta = 76.1; P = 0.05) were significantly associated with deltaPTH. However, upon multivariable regression analysis, only the changes in phosphorus (partial r2 = 0.31; beta = 37.0; P = 0.0001), initial PTH level (partial r2 = 0.23; beta = 0.50; P = 0.0001), and gender (partial r2 = 0.05; beta = 63.1; P = 0.02) remained significantly associated with deltaPTH. Neither the serum concentration of 1,25-dihydroxyvitamin D3, bicarbonate, aluminum, or albumin nor changes in the serum bicarbonate concentration, the presence of diabetes, KT/V, or age were significantly associated with the deltaPTH. Our findings are consistent with independent effects of phosphorus and gender on parathyroid gland function in patients with dialysis-dependent renal failure through mechanisms that remain to be defined.
 ...
PMID:Predictors of short-term changes in serum intact parathyroid hormone levels in hemodialysis patients: role of phosphorus, calcium, and gender. 981 59

Alterations in calcium metabolism can be demonstrated in the course of insulin-dependent diabetes mellitus. In order to clarify if the presence of persistent microalbuminuria (MA) can affect the main parameters of calcium metabolism, we studied 22 diabetic adolescents and young adults with persistent MA and compared them with 24 patients without MA and 24 healthy controls. Mean values of serum calcium, phosphorus and magnesium were similar in diabetic children and young adults without persistent MA and in controls. In addition, the mean values of PTH and 25-OHD, 1,25 (OH)2D3 and OC did not differ between these diabetics and controls. Diabetics with persistent MA showed no significant difference from the values of either controls or the group of diabetics without persistent MA for the mean values of serum calcium, phosphorus and magnesium and PTH. In contrast, diabetics with persistent MA had significantly (p<0.01) lower 25-OHD (26.5+/-5.2 ng/ml) and 1,25 (OH)2D3 (24.7+/-5.6 pg/ml) as well as OC levels (9.8+/-2.5 ng/ml; p<0.001) than controls (38.1+/-4.9 ng/ml, 40.7+/-6.4 pg/ml and 16.5+/-5.8 ng/ml, respectively) and subjects with normoalbuminuria (36.0+/-4.5 ng/ml, 38.8+/-8.9 pg/ml and 14.5+/-3.2 ng/ml). In conclusion, our study suggests that abnormalities in 25-OHD, 1,25(OH)2D3 and OC can be present in diabetic adolescents and young adults with incipient nephropathy.
 ...
PMID:Calcium metabolism in adolescents and young adults with type 1 diabetes mellitus without and with persistent microalbuminuria. 1021 87

In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model), a significant decrease in renal acid excretion, glomerular filtration rate (GFR) and renal plasma flow (RPF) was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg). Four to 6 days after the induction of diabetes (DM), a group of rats were thyroparathyroidectomized (DM + TPTX). Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA) excretion was unchanged in DM (6.19 +/- 0.54), decreased in TPTX (3.76 +/- 0.25) and returned to normal levels in DM + TPTX (5.54 +/- 0.72) when compared to the control group (6.34 +/- 0.14 mumol min-1 kg-1). The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.
 ...
PMID:Effect of thyroparathyroidectomy on urinary acidification in diabetic rats. 1034 77

We report an autopsy case of intravascular lymphomatosis (IVL) that arose after radiation therapy and chemotherapy for an inoperable pancreatic carcinoma. A 66-year-old man who suffered from diabetes mellitus and pancreatic carcinoma presented with aggressive progression of consciousness disturbance and high fever. The laboratory findings disclosed marked thrombocytopenia, hypercalcemia, and elevated serum PTH-related peptide. The patient soon died of ventricular fibrillation due to uncontrollable hypercalcemia. Postmortem examination with immunohistochemical analysis revealed a well-differentiated tubular adenocarcinoma in the pancreatic body as well as an accumulation of neoplastic B-lymphocytes in small vessels throughout the body without systemic lymphadenopathy. To our knowledge, double neoplasms including IVL are extremely rare.
 ...
PMID:[Autopsy case of intravascular lymphomatosis with pancreatic carcinoma]. 1039 Aug 93

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) concentrations have been found to be decreased in diabetic humans and rats. To investigate further the regulation of plasma Ca in diabetes, first we measured Ca(2+), P, Mg, parathyroid hormone(1-34) (PTH), and total and free 1,25(OH)(2)D(3) in male spontaneously diabetic rats 7 and 28 days after the onset of glycosuria. Secondly, we studied changes in the levels of PTH and 1,25(OH)(2)D(3) in response to hypocalcaemia induced by an i.v. infusion of EGTA (2.5%, wt/vol.) for 24 h, and changes in the levels of 1,25(OH)(2)D(3) in response to an i.v. infusion of rat PTH (10 microgram over 24 h) without or with concomitant EGTA infusion (producing hypercalcaemia or normo/hypocalcaemia respectively), in diabetic and control rats. Ca(2+), P, Mg and PTH concentrations remained within the control ranges after 7 and 28 days of glycosuria; 1,25(OH)(2)D(3) concentrations were decreased after 7, but not after 28, days of glycosuria. PTH concentrations showed a similar rise during EGTA-induced hypocalcaemia in control and diabetic rats compared with saline-infused rats, whereas 1,25(OH)(2)D(3) concentrations were unchanged in both groups. Total and free 1,25(OH)(2)D(3) levels were comparably (about 3-fold) increased during PTH, but not during combined PTH and EGTA infusion in control and diabetic rats. Total 1, 25(OH)(2)D(3) concentrations were lower in the diabetic groups infused with saline or PTH than in their respective controls, and there was a similar trend in the PTH+EGTA-infused group; free 1, 25(OH)(2)D(3) levels, however, were normal or increased in the diabetic groups, confirming our previous data. The novel finding of this study is that, despite severe insulin deficiency and altered 1, 25(OH)(2)D(3) levels, the in vivo response of PTH levels to hypocalcaemia and the in vivo response of 1,25(OH)(2)D(3) levels to PTH in diabetic rats are comparable with those found in nondiabetic rats.
 ...
PMID:Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats. 1042 63

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.
Exp Clin Endocrinol Diabetes 1999
PMID:Coincidence of hot thyroid nodules and primary hyperparathyroidism. 1048 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>