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)

It is now recognized that it is casual exposure to sunlight that provides most humans with their vitamin D requirement. During exposure to sunlight, the high energy ultraviolet B photons (290-315 mm) photolyzes cutaneous stores of 7-dehydrocholesterol to previtamin D3. Once formed, previtamin D3 undergoes a thermal isomerization that results in the formation of vitamin D3. Vitamin D3 is biologically inert and requires successive hydroxylations in the liver and kidney to form its biologically active hormone 1,25-dihydroxyvitamin D3. The major physiologic function of 1,25-dihydroxy-vitamin D3 is to maintain blood calcium in the normal range. It accomplishes this by increasing the efficiency of intestinal calcium absorption and mobilizing stem cells to become osteoclasts which, in turn, remove calcium from the bone. It is now recognized that there are a variety of calcium metabolic disorders that are related to defects in the synthesis and metabolism of vitamin D. Chronic granulomatous disorders are often associated with hypercalciuria and hypercalcemia. The mechanism by which this occurs is that activated macrophages within granulomatous tissue, in an unregulated manner, convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Besides its calcemic activity 1,25-dihydroxyvitamin D3 is a potent antiproliferative factor for cells and tissues that possess its vitamin D receptor. This has clinical utility in that 1,25-dihydroxyvitamin D3 and its analogs have been successfully used for the treatment of the hyperproliferative skin disease psoriasis.
Exp Clin Endocrinol Diabetes 1995
PMID:Defects in the synthesis and metabolism of vitamin D. 758 27

To assess the risk factors associated with renal osteodystrophy, we examined the database of 256 patients who were prospectively studied in three Toronto dialysis centers between October of 1987 and 1989. The potential risk factors examined included age, sex, type and duration of dialysis, type and dose of phosphate binders, vitamin D treatment, and history of diabetes mellitus, renal allograft failure, parathyroidectomy, and bilateral nephrectomy. All patients had undergone a bone biopsy and were categorized into one of four disease groupings: (1) osteitis fibrosa and mixed bone disease, (2) aluminum bone disease, (3) mild bone disorder, and (4) aplastic bone disorder. The mean (+/- SD) age of the patients at bone biopsy was 57 +/- 15 years, and 62% were men. Forty-five percent of patients were treated by hemodialysis and 55% by peritoneal dialysis. The mean duration of dialysis was 4 +/- 4 years. Twenty-five percent were also diabetic. The most common disorder was the aplastic (or "adynamic") bone disorder, found in 34% of patients. Aluminum bone disease was found in 27%, osteitis fibrosa or mixed bone disease in 27%, and mild bone disorder in 12% of patients. Cumulative intake of aluminum gels was associated with aluminum bone disease, whereas peritoneal dialysis with supraphysiologic calcium concentrations, ingestion of calcium carbonate, and diabetes mellitus were associated with both mild bone disorder and aplastic bone disorder. These three latter risk factors may be important in predisposing patients to a low bone turnover state through modulation of parathyroid hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Risk factors for renal osteodystrophy: a multivariant analysis. 774 22

Prevention of late-life disability is an important goal in managing the health care of older women. Hormone replacement therapy and regular exercise can protect against osteoporosis and heart disease. Dietary measures can control weight and prevent diabetes. Adequate calcium and vitamin D intake help protect bones from fractures. Mammography and Pap smears are proven screens for early cancer detection. Depression is not unusual in older women, but it is often masked by physical symptoms. Physicians can help women at risk for caregiver burnout by providing referrals and information on community resources. Use of other health professionals, as well as patient education videos and printed materials, can help physicians provide comprehensive care within the time limits of office practice.
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PMID:Older women's health: clinical care in the postmenopausal years. A roundtable discussion part 2. 776 64

Pharmacological amounts of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have potent immunoregulatory activity, but with marked effects on calcium and bone metabolism. In this study we demonstrate that nonhypercalcemia-inducing nondemineralizing doses of an analog of 1,25-(OH)2D3, 1 alpha,25-(OH)2-20-epi-22-oxa-24,26,27-trishomo-vitamin D (KH1060), can prevent type I diabetes. Female NOD mice received 1,25-(OH)2D3 (5 micrograms/kg), KH1060 (0.4 or 0.2 micrograms/kg), or the treatment vehicle ip every 2 days from 21-200 days of age. The incidence of diabetes in controls was 17 of 31 (55%), whereas 7 of 38 (18%) 1,25-(OH)2D3-treated mice, 3 of 27 (11%) KH1060 (0.4 micrograms/kg)-treated mice, and 6 of 27 (22%) KH1060 (0.2 micrograms/kg)-treated mice developed diabetes (P < 0.025 vs. controls). Protection was achieved with the low KH1060 dose without effects on calcium or bone metabolism, as evaluated by serum calcium (9.5 +/- 0.4 vs. 9.4 +/- 0.3 mg/dl in controls; P = NS), serum osteocalcin (82 +/- 17 vs. 83 +/- 20 ng/ml; P = NS), bone calcium content (6.8 +/- 0.7 vs. 6.4 +/- 0.5 mg/tibia; P = NS), urinary calcium (21 +/- 4 vs. 21 +/- 4 mg/dl; P = NS), pyridinoline excretion, and duodenal calbindin-D9K concentration. The proposed mechanism of action is a restoration of suppressor cell activity, as demonstrated in vitro (suppressor cell assay) and in vivo (cell transfer experiments). This study demonstrates that an analog of 1,25-(OH)2D3 prevents type I diabetes in NOD mice without significant effects on calcium or bone metabolism.
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PMID:Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060. 786 94

1,25 dihydroxyvitamin D3, the active form of vitamin D, has immunomodulatory properties in vitro and in vivo. We report that treatment with 1,25 dihydroxyvitamin D3 (5 micrograms/kg on alternate days) prevents the development of clinical diabetes in NOD mice, an animal model of human autoimmune diabetes. Diabetes incidence in female NOD mice at the age of 200 days was reduced to 8% in the 1,25 dihydroxyvitamin D treated group vs 56% in the control group (p < 0.0001). In parallel, treatment with 1,25 dihydroxy-vitamin D3 resulted in a complete normalisation of the capacity to induce suppressor mechanisms in an autologous MLR, which is severely depressed in control NOD mice. The existence of such suppressor cells was confirmed in transfer experiments, whereby cotransfer of splenocytes from 1,25 dihydroxyvitamin D3 treated NOD mice prevented diabetes transfer by splenocytes from diabetic NOD mice into irradiated, 6-8-week-old male NOD mice. Other known immune defects of the NOD mice, such as defective natural killer cell killing of YAC-1 targets and defective thymocyte activation by anti-CD3 were not corrected. The pharmacological doses of 1,25 dihydroxyvitamin D3 were universally well tolerated as reflected by a normal weight gain of the mice. Serum calcium was increased (2.5 +/- 0.2 vs 2.2 +/- 0.2 mmol/l in the control group, p < 0.005), whereas osteocalcin levels nearly doubled and bone calcium content was halved. These findings show that 1,25 dihydroxyvitamin D3 can prevent diabetes in NOD mice, probably through the correction of their defective suppressor function.
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PMID:Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. 792 38

The cytokine interleukin-1 beta (IL-1 beta) has been proposed to be involved in pancreatic beta-cell destruction during the development of autoimmune insulin-dependent diabetes mellitus. It has been demonstrated that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibits T-lymphocyte and monocyte functions in vitro, probably through an effect on cytokine actions, and that in vivo treatment with vitamin D can prevent pancreatic insulitis in diabetes-prone NOD mice. In this study isolated rat pancreatic islets were exposed to human IL-1 beta (25 U/ml) in the absence or presence of 1,25-(OH)2D3 or the analogues MC903 and KH1060 for 48-72 h in tissue culture, whereupon medium insulin accumulation, islet DNA and insulin contents, glucose-stimulated insulin secretion and glucose oxidation rates were assessed. All three vitamin D derivatives counteracted the suppressive effect of IL-1 beta on medium insulin accumulation, 1,25-(OH)2D3 being active at concentrations down to 0.1 nM, i.e., 1-2 orders of magnitude more efficacious than the analogues. However, only KH1060 opposed the suppressive effect of IL-1 beta on islet glucose-stimulated insulin secretion and glucose oxidation rate despite the fact that KH1060 itself reduced the islet DNA and insulin content by approximately 10% and 30%, respectively. The protective effect observed against IL-1 beta-induced beta-cell dysfunction might be related to a beneficial action of vitamin D3 on the mitochondrial calcium metabolism of the beta-cells.
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PMID:Effects of 1,25-dihydroxyvitamin D3 and the analogues MC903 and KH1060 on interleukin-1 beta-induced inhibition of rat pancreatic islet beta-cell function in vitro. 795 6

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

Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes. The test was repeated 0.5, 1, 3 and 5 months after starting treatment. Serum calcium increased glucose intolerance from 1.76 to 2.0, 2.08, 1.96 and 2.0 mmol/l, respectively; vitamin D reached supraphysiological levels initially and returned to normal levels, and parathyroid hormone levels were normalized. Her weight did not change during treatment. Glucose tolerance improved during treatment and achieved glucose was 9.4, 8.6, 9.2 and 9.0 mmol/l at 0.5, 1, 3 and 5 months, respectively; insulin sensitivity did not change. Beta-cell function improved from 101% at diagnosis to 126%, 147%, 173% and 198% at 0.5, 1, 3 and 5 months, respectively. Improvement in beta-cell function and consequently in glucose tolerance is likely to have been due to correction of hypocalcaemia, vitamin D deficiency and secondary hyperparathyroidism.
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PMID:Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D. 802 65

Besides defining the appropriate doses of frusemide in uraemic patients, A. Heidland's contribution to the treatment of hypertension in chronic renal failure consisted in the following demonstrations: (1) In patients on chronic haemodialysis, calcium antagonists have a beneficial effect on their glucose intolerance and decreased plasma levels of 25OH vitamin D while their effect on blood lipids is neutral. (2) In 5/6 nephrectomized rats, captopril, verapamil, and metoprolol have the same protective effect on their GFR and tubular secretion of protons, at equal blood-pressure-lowering effect. (3) In rats with streptozotocin-induced diabetes, atrial natriuretic peptide does not play a role in their hyperfiltration. (4) Severe retinopathy is observed in patients with uraemic nephropathies at a much smaller elevation of their blood pressure than in patients with essential hypertension. This article reviews the following points: (1) The role of hypertension in the loss of renal function is convincingly demonstrated only in a few experimental models, and in man only in malignant hypertension and diabetic nephropathy but not in essential hypertension nor in non-diabetic nephropathy. However, preliminary results suggests that antihypertensive treatment may retard the progression of renal disease in normotensive patients (DBP <90 mmHg) with either microalbuminuric diabetes and normal renal function or non-diabetic uraemic nephropathy. (2) Only the ACE inhibitors have been proved to have a specific renal protective effect, independent of their diurnal blood-pressure-lowering effect, both in diabetic nephropathy and in non-diabetic uraemic nephropathy.
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PMID:Hypertension and progression of renal insufficiency. 807 21

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


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