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)

Vitamin D deficiency reduces insulin secretion and still occurs in East London Asians in whom the prevalence of diabetes mellitus is at least four times that of Caucasians. Vitamin D status was assessed in 44 of 65 non-diabetic subjects 'at risk' of diabetes (spot blood glucose level >6.0 mmol/l <2 h post cibum, or>4.6 mmol/l >2 h post cibum on two separate occasions) and in 15 of 60 age and sex-matched 'low-risk' control subjects who attended for oral glucose tolerance test (OGTT) after screening of 877 omnivorous subjects not known to have diabetes. It was found that 95% of at-risk and 80% of low-risk subjects were vitamin D deficient (serum 25-hydroxy-vitamin D <11 ng/ml). Diabetes was present in 16, impaired glucose tolerance in 12 and normoglycaemia in 19 at-risk subjects, imparied glucose tolerance in 2, and normoglycaemia in 13 low-risk subjects. Correlation of 30-min OGTT blood glucose, specific insulin and C-peptide levels with 25-hydroxy-vitamin D concentrations in 44 at-risk subjects were -0.31 (p=0.04), 0.59 (p=0.0001) and 0.44 (p=0.006). In 15 'not-at-risk' subjects 30-min OGTT specific insulin and C-peptide levels correlated with 25-hydroxy-vitamin D, r=0.39 (p=0.04) and 0.16 (p=0.43), respectively. Serum alkaline phosphatase concentration was higher in at-risk than not-at-risk subjects (59.6 vs 46.5 IU/l, p=0.012); corrected calcium concentrations were comparable (2.38 vs 2.39 mmol/l, p=0.7). Following treatment with 100,000 IU vitamin D by i.m. injection, specific insulin, C-peptide [30 min on OGTT] and 25-hydroxy-vitamin D concentrations had risen 8-12 weeks later [mean +/- DS] from 57 +/- 62 to 96.2 +/- 82.4 mU/l [p=0.0017], 1.0 +/- 0.4 to 1.7 +/- 0.8 pmol/ml [p=0.001] and 3.6 +/- 1.8 to 13.5 +/- 7.4 ng/ml [p=0.0001], (but not to low-risk group values of 179 +/- mU/l, 2.7 +/- 1.14 pmol/ml and 8.16 +/- 6.4 ng/ml), respectively. Both total serum alkaline phosphatase and corrected calcium concentrations rose following vitamin D treatment in the at-risk subjects by 11.1 +/- 8.22 (from 44 to 55 IU/l) and 0.15 +/- 0.18, (2.43 to 2.57 mmol/l), respectively (p=0.004). Abnormal glucose tolerance was unchanged by vitamin D treatment. The value of early and sustained repletion with vitamin D in diabetes prophylaxis should be examined in communities where vitamin D depletion is common.
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PMID:Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. 869 Jan 78

Parathyroidectomy (PTX) is one of the treatments of choice for secondary hyperparathyroidism in chronic dialysis patients. Due to the large increase in long-term dialysis patients, hyperparathyroidism is becoming a common clinical problem. Several studies on PTX have reported various surgical procedures, but limited information is available on the incidence and risk factors of the surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based dialysis registry. It covers the entire area of Okinawa from when the use of chronic dialysis began in 1971. By the end of 1990, a total of 1,986 chronic dialysis patients were registered and 128 of these had undergone PTX by the end of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per 1,000 patient-years. About half of the PTX patients underwent the surgery within 10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase significantly with the duration of dialysis, P < 0.0001. Other clinical variables such as sex, age at the start of dialysis and the presence of diabetes mellitus were not significant predictors of PTX. The probability of PTX increased linearly with the duration of dialysis (r = 0.83, p < 0.0001). After the introduction of active vitamin D in 1981, the probability of PTX was significantly decreased (p < 0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the duration of dialysis, the risk of PTX increased steadily and was estimated to be 10 percent in 10 years and 20 percent in 20 years. Other uremic factors determining a pathological transformation of parathyroid tissue from reactive to autonomous growth remained to be investigated.
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PMID:An epidemiologic analysis of parathyroidectomy in chronic dialysis patients. The Okinawa Dialysis Study Group. 874 93

Subclinical vitamin D deficiency is considered to be a risk factor for osteoporosis. Therefore, we studied vitamin D status and bone mineral density (BMD) in an age- and sex-stratified population based sample (209 males and 206 females aged between 50 and 80 years). In addition, urinary excretion of pyridinium crosslinks of collagen was determined in order to monitor bone resorption. We found a seasonal variation of serum 25-hydroxyvitamin D (25(OH)D) levels with higher values detected in the summer (27 +/ - 10 ng/ml) and lower values measured in the winter (17 +/- 9 ng/ml). Further analyses were performed separately for winter and summer, respectively. We also excluded subjects taking osteotropic medication. In men, we found no significant relationship between vitamin D status and bone density or pyridinium crosslinks. In women, we found significant positive correlations between 25(OH)D and proximal femur BMD in winter (r = 0.21, p < 0.05) and in summer (r = 0.36, p < 0.01). The association between 25(OH)D and proximal femur BMD persisted after correction for age and body mass index. Serum 25(OH)D and urinary pyridinium crosslinks were inversely correlated in females in winter (r = -0.24, p < 0.02) and in summer (r = -0.32, p < 0.02). Our data support the hypothesis that already moderately low serum levels of 25(OH)D within the "normal" range lead to osteopenia via increased bone resorption.
Exp Clin Endocrinol Diabetes 1996
PMID:Lower serum 25-hydroxyvitamin D is associated with increased bone resorption markers and lower bone density at the proximal femur in normal females: a population-based study. 881 49

Peritoneal dialysis (PD) has gained recognition worldwide as an alternative to haemodialysis in the management of patients with end-stage renal disease. Because the peritoneal catheter provides direct access to the peritoneum, intraperitoneal drug administration has become widely used for the administration of certain drugs. The instillation and drainage of PD fluids contribute to the total body clearance of drugs given by other routes. For most drugs, peritoneal clearance is low. This paper provides an updated review of recently published pharmacokinetic studies involving the administration of selected drugs to patients receiving PD. Antibiotics continue to be extensively studied and administered in PD patients because of the frequent occurrence of infections. Epoetin (recombinant human erythropoietin) has become widely used and is the subject of ongoing pharmacokinetic investigation. Intraperitoneal insulin has become accepted for the treatment of patients with diabetes receiving PD; the pharmacokinetics of vitamin D analogues in PD patients continue to be explored.
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PMID:Clinical pharmacokinetics during continuous ambulatory peritoneal dialysis. 889 45

The therapeutic effect of most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral, bacterial or fungal organisms as well as by an increased incidence of malignant neoplasms. This short review includes the most commonly used immunosuppressants such as corticosteroids, azathioprine, methotrexate, cyclophosphamide and cyclosporine. The most common risks of long-term corticosteroid treatment are Cushing-like changes, decreased glucose tolerance and the usually benign steroid diabetes. Also clinically important is osteoporosis, since it can be prevented by physical training, calcium supplementation and treatment with vitamin D if necessary. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastrointestinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and prednisone, whereas with synthetic steroids such as dexamethasone, sodium retention is absent despite their strong antiphlogistic activity. The most important side effect of the cytotoxic agents azathioprine, methotrexate and cyclophosphamide is marrow suppression. Due to the high turnover of neutrophils, patients most frequently suffer neutropenia rather than thrombocytopenia or anemia. Neutropenia, as well as impaired humoral and cellular immune mechanisms, are responsible for increased susceptibility to bacterial, viral or parasitic diseases during immunosuppressive therapy. Hepatotoxicity has been reported among patients receiving azathioprine (cholestatic hepatitis) and methotrexate (elevated AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphamide causes hemorrhagic cystitis in a substantial proportion of patients, as well as an increased incidence of urothelial neoplasms. Both these side effects may be prevented by Mesna. The most important side effects of cyclosporine are acute and chronic nephrotoxicity usually associated with significantly elevated plasma levels of the drug. It must be borne in mind that severe nephrotoxicity may occur in patients receiving cyclosporine and ketoconazole together, since the latter may inappropriately increase the plasma cyclosporine level.
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PMID:[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. 892 65

To explore the pathogenesis of non-insulin-dependent diabetes mellitus associated osteopenia, we examined age-related changes of the femur metaphyseal bone mineral density in genetically diabetic (db/db) mice and non-diabetic (+/+) mice of the same strain using single photon absorptiometry and characterized the osteopenia pharmacologically and biochemically. Bone mineral density increased with age in the +/+ mice from 5 to 16 weeks of age, but reached a plateau in the db/db mice at 8 weeks of age, and significant differences between the two groups were observed after 12 weeks of age. Ash weight (A) and dry weight (D) of the femur and A/D ratio were significant lower in the db/db mice than in the +/+ mice after 8 weeks of age. Significant elevations of serum calcium and parathyroid hormone (PTH) were observed after 8 weeks and 12 weeks of age, respectively. Serum 1alpha,25-dihydroxyvitamin D levels were significantly decreased in the db/db mice compared to the +/+ mice. Daily oral treatment with 1alpha-hydroxyvitamin D3 (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated the bone loss in the db/db mice. These results suggest that an impaired bone mineralization probably by insufficient vitamin D activity and high PTH levels are involved in the osteopenia in the db/db mice. 1alpha-(OH)D3 exerted beneficial effects on the bone loss.
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PMID:Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group. 900 43

Vitamin D status was assessed in 142 elderly Dutchmen participating in a prospective population-based study of environmental factors in the aetiology of non-insulin-dependent diabetes mellitus. Of the men aged 70-88 years examined between March and May 1990, 39% were vitamin D depleted. After adjustment for confounding by age, BMI, physical activity, month of sampling, cigarette smoking and alcohol intake the 1-h glucose and area under the glucose curve during a standard 75-g oral glucose tolerance test (OGTT) were inversely associated with the serum concentration of 25-OH vitamin D (r = -0.23, p < 0.01; r = -0.26, p < 0.01, respectively). After excluding newly diagnosed diabetic patients total insulin concentrations during OGTT were also inversely associated with the concentration of 25-OH vitamin D (r = -0.18 to -0.23, p < 0.05). Hypovitaminosis D may be a significant risk factor for glucose intolerance.
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PMID:Vitamin D, glucose tolerance and insulinaemia in elderly men. 908 75

Glucocorticoids are amongst the most potent immunosuppressant drugs available and are widely used in many inflammatory and autoimmune conditions such as asthma and systemic lupus erythematosus. These agents are, however, associated with potentially substantial systemic side effects including electrolyte disturbances, cardiovascular effects, diabetes mellitus and loss of bone density and osteoporosis with concomitant vertebral fracture. The clinical utility of these agents should be tempered by the use of a minimum effective dose and, where possible, by the administration of alternate daily or pulse steroids which may have some impact on reducing the prevalence of these adverse effects. Moreover, recent evidence suggests that calcium and vitamin D co-administration may offset the chronic effects of glucocorticoids in inducing bone loss. A greater understanding of the molecular and cellular basis of glucocorticoid action, particularly as it relates to bone loss, is necessary to optimize efficacy and safety and to utilize therapies which may minimize the long-term effects of glucocorticoids. Furthermore, there is a need to develop newer glucocorticoids which have lesser effects on bone and other sites of adverse events, whilst retaining their immunosuppressive and anti-inflammatory action.
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PMID:An overview of the adverse reactions to adrenal corticosteroids. 911 47

Hypoparathyroidism is a rare disease with hypocalcemia as the leading symptom. In adults, hypocalcemia is mainly due to postoperative hypoparathyroidism. Hypoparathyroidism requires lifelong therapy with vitamin D or metabolites. Genuine vitamin D3 (Vigantol) is the most economic treatment of hypoparathyroidism; however, vitamin D3 has a very long biologic half life with the subsequent danger of chronic vitamin D intoxication. Dihydrotachysterol (A.T.10), an analogue of vitamin D, acts similarly and can be used alternatively. 1,25-dihydroxyvitamin D3 (Rocaltrol), the biologically active metabolite of vitamin D3, is very potent, but bears the danger of causing acute intoxication; it has a short half life and is more expensive than vitamin D3. A further metabolite, 1-hydroxy-vitamin D3 (alfacalcidol, Doss, EinsAlpha) is available for therapeutic use. Clinical intervention trials concerning the best therapy and management of hypoparathyroidism are lacking. We therefore surveyed German physicians treating hypoparathyroidism. Furthermore, we carried out a retrospective study of 45 patients treated in our endocrinology department during the last 8 years and examined whether measurement of 25(OH)-vitamin D3 is helpful in managing hypoparathyroidism. The data from 59 children and 270 adults could be completed in the survey. 1,25-dihydroxyvitamin D3 was the only vitamin D agent that was administered in the treatment of children, whereas in adults 52% were treated with dihydrotachysterol, 28% with genuine vitamin D3, and 20% with 1,25-dihydroxyvitamin D3. There was a positive correlation between serum 25(OH)-vitamin D3 levels and administered vitamin D3 doses. In patients treated with vitamin D3, serum calcium levels correlated significantly with serum 25(OH)-vitamin D3 levels whereas they did not correlate with administered calcium doses. Thus: (1) in Germany dihydrotachysterol is preferred for therapy of hypoparathyroidism in adults and (2) measurement of serum 25(OH)-vitamin D3 may be helpful in assessing efficacy of therapy and compliance in patients treated with vitamin D3.
Exp Clin Endocrinol Diabetes 1997
PMID:Current therapy of hypoparathyroidism--a survey of German endocrinology centers. 928 13

Vascular calcification (VC), which is described in the elderly and in diabetics, is frequently seen in uraemia. It is usually regarded as having little significance. We studied the roentgenological appearance of VC in a homogeneous group of 38 long-hours haemodialysis patients whose longevity on dialysis allowed sustained (10-25 years) follow-up, including annual skeletal surveys and thrice-yearly clinical examinations and biochemical profiles. We compiled a dossier of clinical and laboratory parameters from the start of dialysis to the present day. We were able to analyze the natural history of VC and to determine which clinical parameters were linked with progression. We found that VC became steadily more prevalent-at dialysis onset present in 39% of the patients, but in 92% after an average dialysis duration of 16 years, with a mean onset 9.7 years after starting dialysis. As well as becoming more prevalent, the calcification became progressively more severe in most patients. There were two patterns of VC: axial (aorta and iliac and femoral arteries), seen alone in 32% of the patients, and peripheral (digital arteries), seen alone in 3% of patients. Most patients (65%) had evidence of both types. Calcification was scored for site and severity. Patient age (r = 0.57, p < 0.001), systolic blood pressure (r = 0.54, p < 0.001), hyperparathyroidism (reduced progression after parathyroidectomy), plasma phosphate (r = 0.34, p = 0.042), and vitamin D concentrations (r = 0.53, p < 0.001) were the principal determinants of severity and rate of progression of VC in this population. There was a weak negative association between progression and serum ferritin (r = -0.33, p = 0.046). The reduced vessel compliance that results from VC is likely to be cardiovascularly deleterious. In severe cases, tissue perfusion or vascular access for haemodialysis can be compromised. VC and accelerated cardiovascular mortality are common to uraemia, diabetes, and systolic hypertension in the elderly. Better understanding of these pathological processes may permit intervention and possibly lead to a reduction in cardiovascular mortality.
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PMID:Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis. 938 Feb 36


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