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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorus is the sixth most abundant element in the body after oxygen, hydrogen, carbon, nitrogen, and calcium. It comprises about 1% of the total body weight of humans. Eighty-five percent of it is stored in the bone in the form of hydroxyapatite crystal; 14% is in the soft tissues in the form of energy-storing bonds with nucleotides (ATP, GTP), nucleic acids in chromosomes and ribosomes, 2,3-DPG in the red blood cells, and phospholipids in the cells' membranes. Less than 1% is in the extracellular fluids. Phosphate balance is maintained by multiple systems. The gut is responsible for the absorption of two thirds of the 4-30 mg/kg/day of phosphate intake. Absorption sites are all along the gut; in humans the most active site is the jejunum. The kidney filters 90% of the plasma phosphate and reabsorbs it in the tubuli. In states of hypophosphatemia the kidney can reabsorb the filtered phosphates very efficiently, reducing the amount excreted in the urine virtually to zero. The healthy kidney can excrete high loads of phosphate and rid the body of phosphate overload. Through the vitamin D-PTH axis the endocrine system regulates the phosphate balance by influencing the kidney, gut, and bone. Other hormones, including thyroid, insulin, glucagon, glucocorticosteroid, and thyrocalcitonin, play a lesser role in regulation of phosphate metabolism. Because of the complex control of phosphate homeostasis, various clinical conditions may lead to hypophosphatemia. These include nutritional repletion, gastrointestinal malabsorption, use of phosphate binders, starvation, diabetes mellitus, and increased urinary losses due to tubular dysfunction. The clinical picture of phosphate depletion is manifested in different organs and is due mainly to the fall in intracellular levels of ATP and decreased availability of oxygen to the tissues, secondary to 2,3-DPG depletion. The various manifestations of phosphate depletion are listed in Table 2. The treatment of hypophosphatemia consists of administering enteral or parenteral phosphate salts. An important aspect of dealing with the potentially serious effects of phosphate depletion is to prevent the depletion from happening in the first place. Hyperphosphatemia can occur in renal failure, hemolysis, tumor lysis syndrome, and rhabdomyolysis. The treatment of hyperphosphatemia usually consists of fluid administration (in the absence of kidney failure). In chronic hyperphosphatemia, phosphate binders such as aluminum and magnesium salts can reduce the phosphate load. The use of these phosphate binders is limited by their potential side effects.
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PMID:Consequences of phosphate imbalance. 306 Jan 61

The etiology of diabetic osteopenia has not been established. The value of serum osteocalcin (BGP) as a marker of the bone abnormalities and the possible role of the polyol pathway in diabetic osteopenia were investigated. Three groups of rats were studied over 7 weeks: group D (n = 12), rats with streptozotocin (55 mg/kg)-induced diabetes given saline by gavage; group DS (n = 12), rats with streptozotocin-induced diabetes given the aldose reductase inhibitor sorbinil (25 mg/kg) daily by gavage; and group C (n = 6), saline-injected controls. Circulating levels of ionized calcium, BGP, amino-terminal PTH, and glucose were measured on days 0, 7, 14, 28, and 49. Tibial bone specimens were examined for the presence of aldose reductase by immunocytochemistry and by histomorphometry after tetracycline labeling. Diabetic rats with or without sorbinil treatment failed to gain weight [group D, 234 +/- 26 g; group DS, 217.0 +/- 40 g; group C, 310 +/- 33 g (mean +/- SD)]. Serum BGP levels decreased significantly in the diabetic rats within 7 days and remained lower throughout the study. BGP values on day 7 were: group D, 47.7 +/- 4.9 ng/ml; group DS, 65.9 +/- 5.5 ng/ml; and group C, 90.4 +/- 4 ng/ml (mean +/- SEM). Serum PTH levels were similar in all groups, except for day 49, when an increase in the D group was observed. Bone histomorphometry showed decreased bone remodeling in the D group, which confirmed the serum BGP findings. Aldose reductase was detectable in the small blood vessels and in bone itself. Sorbinil failed to influence the biochemical or bone histomorphometric abnormalities associated with diabetes. Serum BGP may be a valuable marker for the decreased bone remodeling in insulinopenic diabetes.
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PMID:Bone mineral metabolism in experimental diabetes mellitus: osteocalcin as a measure of bone remodeling. 313 94

The adenosine-receptor antagonist 8-phenyltheophylline (8-PTH) was used to study the role of endogenous adenosine in modulating insulin-stimulated myocardial glucose uptake (MGU) in vivo. Dogs were surgically instrumented under pentobarbital sodium anesthesia to measure hemodynamics and obtain blood samples for determinations of oxygen and glucose concentrations. Myocardial uptake of these substances was calculated as the product of the appropriate arterial-coronary sinus differences and circumflex blood flow. The response to insulin was determined with the hyperinsulinemic-euglycemic clamp technique. During insulin infusion, MGU increased from 3.12 +/- 0.8 to 9.20 +/- 1.8 mg/min (mean +/- SE). In contrast, insulin failed to increase MGU when 8-PTH was being infused into the circumflex artery. These results demonstrate that some degree of adenosine-receptor-mediated activity is required for insulin to stimulate myocardial glucose uptake. It is suggested that the presence of adenosine at its receptor may be an important factor during conditions in which myocardial insulin resistance may develop.
Diabetes 1988 Jun
PMID:Adenosine is required for myocardial insulin responsiveness in vivo. 329 2

Metabolic studies were performed in streptozotocin-induced diabetic (D) rats and normal control (C) rats to assess the role of hyperphagia in the hypercalciuria of diabetes. Urinary calcium excretion (UCaV) was significantly higher in D v C rats fed ad libitum. When D rats were pair-fed (calorie and mineral restriction) with C rats, UCaV declined but remained significantly higher than in C rats. When D rats were allowed their usual increased calorie intake but restricted to C rat mineral consumption, UCaV remained elevated. These findings suggested a tubular reabsorptive defect. In vivo microinjection studies were then performed to identify the site(s) of the tubular reabsorptive defect. Using 1.0 mmol/L Ca in the injectate, 45Ca recovery in the urine (CaR%) was significantly higher in D rats after intratubular injections into early and late proximal tubules and late distal but not early distal tubules. An additional load-dependent defect was revealed in the terminal nephron when the Ca concentration of the injectate was increased to 1.8 mmol/L. After early distal injection, CaR% was significantly increased in D v C rats. Infusion of PTH into thyroparathyroidectomized C and D rats enhanced Ca absorption to a similar degree but did not correct the reabsorptive defect in D rats. These results argue against a lack of end-organ responsiveness to PTH in diabetes or a low serum PTH level as the cause of the hypercalciuria. We conclude that hyperphagia contributes to the hypercalciuria of diabetes in the absence of increased Ca intake. Also, two tubular reabsorptive defects exist: one in the loop of Henle; the other, load-dependent in the terminal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The mechanism of hypercalciuria in streptozotocin-induced diabetic rats. 335 15

Double photon absorptiometry comparison was done of lumbar bone mineral content (BMC) values in 40 women with well-compensated non-insulin-dependent diabetes mellitus (type II) and on dietary and/or oral hypoglycemic treatment, and 35 age-matched non-diabetic women, to determine the presence and degree of osteoporosis in this type of diabetes by means of a highly precise and sensitive method. No difference between the two groups was noted as regards blood calcium, phosphorus, PTH and thyrocalcitonin, and urinary calcium and phosphorus. BMC, on the other hand, was significantly lower in the diabetics, both in L2,L3,L4 and in L4 alone. No significant difference could be discerned between patients on diet and those on drugs. It can thus be maintained that osteoporosis is a possible complication of type II diabetes and may appear even in the absence of its classical complications.
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PMID:Osteoporosis in type II diabetes. 343 1

Osteoporosis is a known complication of diabetes mellitus, suggesting a role for insulin in bone homeostasis. We studied insulin receptors and insulin action in the osteoblast-like rat osteogenic sarcoma cell line ROS 17/2.8. These cells share many common features with the osteoblast, such as 1,25-dihydroxyvitamin D3 receptors, PTH receptors, and 1,25-dihydroxyvitamin D3-induced modulation of alkaline phosphatase activity and osteocalcin. Competition binding studies revealed high affinity insulin receptors, with an ED50 for insulin of 1 nM. The receptors were highly specific for insulin, with 60% inhibition of insulin binding by an antireceptor antibody, no competition by epidermal growth factor, and an ED50 of 300 nM for proinsulin. Steady state maximal insulin binding was obtained by 40 min at 37 C, and insulin degradation, as measured by trichloroacetic acid solubility, was 1%/h at 37 C. ROS cells readily internalized insulin, and under steady state binding conditions at 37 C, 56% of the cell-associated radioactivity consisted of intracellular material. Chloroquine (100 microM) inhibited intracellular processing of insulin, leading to a 300% increase in cell-associated insulin by 2 h (37 C). Photoaffinity labeling of the insulin receptor with the photosensitive analog of insulin, B2 (2-nitro-4-azidophenyl-acetyl)des-pheB1-insulin, followed by solubilization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed specific bands of 125K and 430K mol wt under reducing and nonreducing conditions, respectively. Thus, the structure of insulin receptors in ROS cells appears comparable to that of insulin receptors of known target tissues. Insulin action was also examined. Insulin did not stimulate [2-3H]deoxyglucose uptake or [1-14C]leucine incorporation into protein. In contrast, physiological concentrations of insulin inhibited alkaline phosphatase activity in nonconfluent cells. After exposure to insulin for 24 h, alkaline phosphatase activity was decreased compared to basal by 39.5% and 50% with 5 and 50 ng/ml insulin, respectively. In conclusion, ROS cells bind insulin to specific receptors that are similar to insulin receptors on other target tissues; receptors internalize insulin, which is then processed through a chloroquine-sensitive pathway; insulin does not affect membrane substrate transport; and insulin does inhibit the activity of an enzyme that is important in bone metabolism. ROS cells represent a model for studying insulin effects on bone.
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PMID:Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. 353 Jul 24

We studied phosphorus and calcium metabolism in 50 adult insulin dependent and non insulin dependent diabetics arranged in 4 groups according to therapy and control of diabetes. We observed: a low level of blood magnesium in all diabetics a lower level of P T H, more pronounced with poorly controlled diabetes. a decrease of 1-25 (OH) 2 D levels without modification of the 25 (OH) D levels in badly controlled diabetics. This decrease may be related to the low level of PTH with a 1 alpha hydroxylation defect. These results are in favor of the hypothesis of a primary bone problem leading to the pre-senile and subclinical osteoporosis observed in diabetics. Hyperglycaemia rather than insulinopenia may be involved. Rigorous diabetes control significantly decreases all the observed differences, except the low magnesium level.
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PMID:[Calcium and phosphorus metabolism in insulin dependent and non-insulin dependent diabetics, well-controlled and poorly-controlled]. 384 Oct 78

The first study compared two groups on dialysis: 25 patients with diabetes mellitus and 25 matched non-diabetic patients, in relation to the presence of signs of hyperparathyroidism, to assess the reported low incidence of hyperparathyroidism in these patients. The diabetic group showed significantly lower values of PTH, Alk phosphatase, percentage of patients requiring vitamin D treatment, and less evidence of hyperparathyroidism on X-ray and in bone histomorphometry. In the second study 16 patients with chronic renal failure due to diabetic nephropathy were compared to 27 patients with the same degree of renal failure of other origin, the diabetic nephropathy group showed no increase in PTH, with falling creatinine clearance. Despite this low PTH, the phosphaturia was higher in the diabetic nephropathy group (Tm PO4/C Cr: 1.94 +/- 0.43 vs 2.5 +/- 0.68). In conclusion, patients with diabetes mellitus are less prone to develop hyperparathyroidism in progressive renal failure. This could be due to a relative increase in phosphaturia during declining function.
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PMID:Low incidence of hyperparathyroidism in diabetic renal failure. 399 89

In a university-affiliated community hospital, medical records of 58 patients on whom the intact parathyroid hormone immunoassay (I-PTH) and 29 patients on whom both the carboxyl terminal PTH(C-PTH) and I-PTH ordered by physicians were reviewed to determine the reasons for requesting these tests. Reasons for ordering the PTH tests include (1) the evaluation of hypercalcemic patients (25/58 I-PTH); (2) the evaluation of hypocalcemic patients (2/58 I-PTH); (3) to rule out primary hyperparathyroidism in normocalcemic stone formers (4/58 I-PTH, 4/29 C-PTH) and in those with abnormal skeletal x-ray (3/48 I-PTH 1/29 C-PTH); (4) to follow patients with chronic renal failure on dialysis (11/58 I-PTH, 9/29 C-PTH); (5) to rule out ectopic hyperparathyroidism in patients with cancer (2/58 I-PTH, 3/29 C-PTH); (6) to satisfy physicians' intellectual curiosity of patients with diabetes mellitus (3/58 I-PTH, 3/29 C-PTH) and obesity (5/58 I-PTH; 6/29 C-PTH); (7) to evaluate acute renal failure (1/29 C-PTH). In 3/58 patients on whom I-PTH tests were ordered, reason(s) could not be determined. The C-PTH was elevated in 9/9 patients with chronic renal failure, 4/6 obese patients, 2/3 patients with cancer, 1/3 diabetic patients, 1/4 stone formers, 2/2 patients with primary hyperparathyroidism. Patients with chronic renal failure had the highest C-PTH. Based on well established indications for ordering the PTH immunoassays, 25 out of 58 (43%) of I-PTH and 9 out of 29 (31%) of C-PTH ordered are inappropriate.
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PMID:Diagnostic utility of carboxyl-terminal and intact parathyroid hormone immunoassays in hospitalized patients. 709 Oct 50

Groups of 14 diabetic and 30 nondiabetic patients undergoing maintenance hemodialysis were compared as to levels of serum creatinine, heights of PTH elevation, and finally as to severity of peripheral neuropathy. Diabetics had a statistically lower predialysis serum creatinine, PTH, and MNCV than did nondiabetics. The dual metabolic derangements of uremia and diabetes, along with multiple metabolic aberrations, including PTH, may explain the more severe neuropathy observed in diabetics. A proportionately lower PTH elevation in the diabetic is characteristic of this subgroup of uremic patients.
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PMID:Lower parathyroid hormone and creatinine in diabetic uremia. 739 34


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