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)

Magnesium (Mg) makes up 0.5-1% of bone ash and is therefore not a trace element in the skeleton. Mg influences both mineral and matrix metabolism in bone by a combination of effects on hormones and other factors that regulate skeletal and mineral metabolism, and by direct effects on bone itself. The skeletal content of Mg is very variable both between and within species, and reported values range between 150 and 440 mmol/kg ash weight (AW). Dietary Mg has a direct influence and age an inverse influence on skeletal Mg content. It is unclear whether skeletal Mg content varies from region to region. In humans, reported values cluster around the 200 mmol/kg AW level, 30-40% lower than most rat data. Human iliac crest cortical bone has 10-20% less Mg per unit weight than iliac crest trabecular bone. Mg depletion adversely affects all phases of skeletal metabolism. In the rat, cessation of bone growth is noted with a decrease in both osteoblast and osteoblast activity, decreased bone formation, osteopenia, increased fragility and development of a form of 'aplastic bone disease'. The epiphyseal growth plate is thinned and the percent ash weight of the growth plate is increased, possibly due to enhanced crystallization of bone salt under conditions of Mg depletion. In contrast, in chicks and in rats with severe Mg deficiency, these 'antianabolic' effects are not observed but instead, predominant inhibition of bone resorption occurs with increased cortical thickness rather than osteopenia, and the occasional development of subperiosteal hyperplasia or of fibrous tumors of the periosteum. It is probable that this unusual response under conditions of severe Mg deficiency is in part an indirect effect secondary to a defect in secretion and/or skeletal responsiveness to parathyroid hormone (PTH) and vitamin D metabolites. Mg excess also has adverse biologic effects on bone. Crystallization of bone salt is severely impaired and an osteomalacia-like picture may be produced with decreased osteoblastic activity, widened growth plates, excessive osteoid seams and short, thickened bones. In some studies, especially in mice, Mg excess stimulates bone resorption, independently of PTH. The role of Mg deficiency and excess in human skeletal conditions requires more extensive investigation. Bone Mg is uniformly increased in renal insufficiency and may play a role in renal osteodystrophy since improvement has been noted in the osteomalacic component by normalizing the serum Mg. Decreased bone Mg has been reported in alcoholic patients, diabetes and in osteoporosis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of magnesium on skeletal metabolism. 218 30

The aging process alters body composition so that nutritional status changes as we get older. The aging process shows interindividual variability in its rate of development. Determinants of the rates of aging of systems and tissues are largely genetic. Premature aging of cells and tissues is due to genetic factors and to long-term exposure to physical or chemical environments that cause irreversible tissue damage. Whereas maximal lifespan is fixed for us all, individuals vary in life expectancy both because of variability in the risk of genetic disease which shortens life and because of variable capability for avoidance of those factors in our environment which cause early aging. Early aging as well as geriatric disease foreshorten life, but both can be prevented to some extent by diet or by diet and exercise. Diseases that can be nutritionally prevented, giving us a greater chance of achieving our genetically determined lifespans, include nutritional deficiency states and chronic diet-related diseases such as non-insulin-dependent diabetes, hypertension, coronary artery disease, and cancer. Disabilities resulting from these diseases and from degenerative arthritis are also subject to modulation by diet. The nutritional requirements of the elderly are mostly similar to those of younger people. Elderly usually need fewer calories and similar nutrient intakes compared with those of younger people. Elderly with higher needs for specific nutrients include homebound or institutionalized people who lack sunlight exposure and therefore require more vitamin D. Nutritional requirements to promote longer life expectancy and freedom from disabilities that result from chronic disease include restriction of food energy and fat. Nutritional assessment of the elderly is aimed at identifying not only the presence of deficiency states but also states of nutrient excess and chronic diet-related diseases. There are certain problems in carrying out nutritional assessment in the elderly, but techniques are now available which make valid assessment possible even in the oldest old. Those who live longest have less genetic risk of premature aging, but as a result of native intelligence, education, coping skills, and higher socioeconomic status, they also have a greater likelihood of eating a diet that best meets their long-term nutritional needs. Those most at risk for developing malnutrition as they get older are those who lack food access because of poverty, because of disability resulting from chronic geriatric disease, or because of a combination of these factors. Malnutrition is found in elderly in our society who live in their own homes if they are indigent, isolated, and homebound because of disability.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Geriatric nutrition. 218 27

The author presents an account on possibilities of prevention of osteoporosis and osteomalacia in diabetics by eliminating or reducing some causes which lead to these complications. In osteoporosis this involves a modified diabetic diet, burdening of the bones by suitable exercise, compensation of diabetes and screening and treatment of complications of diabetes. Prevention of osteomalacia in diabetics includes according to the author adequate exposure to ultraviolet rays which ensures an adequate amount of vitamin D in the skin, dietary measures and administration of vitamin D, treatment of complications of diabetes and methods of mobilization of the patients.
 ...
PMID:[Diabetic osteopathy. 5. Prevention]. 224 72

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.
 ...
PMID:Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study. 240 31

Calcium homeostasis was investigated in male BB rats with a diabetes duration of 3-4 weeks and compared with that in nondiabetic littermates either fed ad libitum or receiving selective semistarvation or an oral Ca supplement to obtain additional weight-matched and Ca intake-matched control groups. Diabetic rats had markedly increased food and Ca intake, so that their net Ca balance remained positive despite a 13-fold increase in urinary Ca excretion and a disappearance of active duodenal Ca absorption. Decreased duodenal Ca uptake correlated with decreased 1,25-(OH)2D3 levels (89 +/- 15 vs. 160 +/- 13 pg/ml in nondiabetic rats), decreased duodenal 9K Ca-binding protein concentrations (10 +/- 1 vs. 21 +/- 2 micrograms/mg protein), and decreased number of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-binding sites in duodenum, although the binding affinity was above normal. Nondiabetic Ca-supplemented rats exhibited a similar response: decreased 1,25-(OH)2D3 (95 +/- 8 pg/ml) and 9K Ca-binding protein (7 +/- 0.5 micrograms/mg protein) concentrations, decreased active duodenal Ca uptake, increased urinary Ca excretion, and a normal net Ca balance. Plasma vitamin D-binding protein levels were decreased by 62% in diabetic rats, due to a marked decrease in production rate, while the plasma half-time remained normal. The free 1,25-(OH)2D3 index was highest in diabetic rats, suggesting partial vitamin D resistance at the duodenal level. In semistarved rats, 1,25-(OH)2D3 levels and active Ca uptake remained normal, and the free 1,25-(OH)2D3 index was increased, together with suppressed vitamin D-binding protein levels. These studies indicate that nutritional abnormalities may contribute to but cannot totally explain the disturbances in vitamin D metabolism, transport, or action at the intestinal level.
 ...
PMID:Bone mineral homeostasis in spontaneously diabetic BB rats. I. Abnormal vitamin D metabolism and impaired active intestinal calcium absorption. 253 13

A variety of age-related anatomic and functional alterations in the kidney have been described. Anatomic abnormalities in the aging kidney include a decrease in kidney size, increased glomerular sclerosis, altered tubular structure, and an altered pattern of vascular flow. These anatomic abnormalities are associated with renal functional abnormalities, including decreased renal blood flow, and glomerular filtration rate. Altered renal tubular function, including impaired handling of water, sodium, acid, and glucose, may also be present. Impaired "endocrinologic" functioning manifested by changes in the renin-angiotensin system, vitamin D metabolism, and antidiuretic hormone responsiveness have been reported. The kidney is constantly exposed to the effects of a variety of potentially toxic processes. These range from environmental toxins and drugs, to a variety of chronic medical illnesses including hypertension, diabetes, and atherosclerotic disease. In this context, differentiation of "aging" effects from nephrotoxic effects resulting from these other processes is difficult. It has been argued that hypertension is an important factor in the development and progression of renal insufficiency in the elderly. The relationship between hypertension, glomerular hyperfiltration, atherosclerosis, and progressive renal dysfunction needs further study. Further research may allow the rational recommendation of interventions designed to control age-associated changes in renal function.
 ...
PMID:Renal function in aging. 266 87

Several studies have reported association between noninsulin-dependent diabetes mellitus and GC, the vitamin D binding protein of human plasma, with the GC 1 allele in significant excess among diabetics. Additionally, there is a considerable body of animal data suggesting that vitamin D has a significant impact on insulin secretion. Examination of the insulin levels in Dogrib Indians showed that the lowest levels of fasting insulin were associated with the GC IF-IF genotype. The present study examined levels of glucose, C-peptide, and insulin at fasting and 1 hr and 2 hr following a 75 g oral glucose challenge, in a population of Hispanic-Americans and Anglos in the San Luis Valley of southern Colorado. The sample comprised a total of 468 individuals with normal glucose tolerance. Of these, 289 were Anglos and 179 were Hispanic-Americans. An analysis of covariance was performed to determine the effect of the GC genotypes on mean levels of the primary variables--glucose, C-peptide, and insulin--and a secondary variable--insulinogenic index adjusting for the covariates age, body mass index (BMI), gender, and ethnicity. The analyses revealed that there is a significant difference in mean levels of glucose at fasting (F value = 2.46; P = 0.033) among the GC genotypes in the sample. Additionally, the differences in mean levels of 1 hr postprandial glucose among the GC genotypes although not significant at a 5% level, were significant at the 10% level. No other significant phenotypic effects were observed. These analyses are not in concordance with the results of an earlier study, where lower fasting insulin was associated with the GC 1F-1F genotype.
 ...
PMID:On the role of vitamin D binding globulin in glucose homeostasis: results from the San Luis Valley Diabetes Study. 269 26

There are specific receptors for the active metabolite of vitamin D on the pancreatic beta cells and severe vitamin D deficiency can inhibit insulin secretion. In the present study 14 middle aged men with impaired glucose tolerance and low glucose-stimulated insulin values received 2 micrograms alphacalcidol daily for 18 months. On treatment there was a transient increase of both the peak and the late insulin response to intravenous glucose while neither intravenous nor oral glucose tolerance were consistently altered. Nor was the peripheral insulin sensitivity, measured by the euglycemic clamp technique, significantly affected. In the untreated state there was a positive relationship (r = 0.77) between the tissue insulin sensitivity and the serum concentrations of 25-hydroxyvitamin D. There was also an inverse relationship (r = 0.61) between systolic blood pressure and the serum levels of 1,25-dihydroxy vitamin D. Although the subjects were normotensive and not overweight, treatment with alphacalcidol tended to lower both systolic (6 +/- 12 mmHg) and diastolic blood pressures (5.8 +/- 9.1 mmHg) and there was a small reduction (0.9 kg) in body weight. In conclusion, subjects with impaired glucose tolerance without vitamin D deficiency do not benefit from vitamin D supplementation, which however has some hypotensive action also in normotensive individuals.
Diabetes Res 1989 Jul
PMID:Long-term treatment with active vitamin D (alphacalcidol) in middle-aged men with impaired glucose tolerance. Effects on insulin secretion and sensitivity, glucose tolerance and blood pressure. 269 85

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.
 ...
PMID:Bone demineralization and impaired mineral metabolism in insulin-dependent diabetes mellitus. A possible role of magnesium deficiency. 278 12

In previous studies on calcium homeostasis in diabetes, drug-induced diabetic rats have generally been used, and various alterations have been demonstrated in several parameters of the vitamin D-endocrine system. It is, however, still questionable whether the drug-induced diabetic rat is the most appropriate animal model for the investigation of calcium and vitamin D metabolism because of the toxicity of diabetogenic agents toward the principle organs of vitamin D metabolism, such as liver and kidney. Therefore, in the present study, we examined the strain of genetically diabetic mice, C57BL/KsJ db/db, to evaluate 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors in intestine and kidney and to investigate the alterations of calcium and vitamin D metabolism. In both control and diabetic mice, intestinal and renal 1,25-(OH)2D3 receptors were demonstrated; they had a sedimentation coefficient of 3.4S. The number of specific 1,25-(OH)2D3-binding sites in intestine was 118 +/- 11 fmol/mg protein in diabetic mice, significantly lower than the value of 199 +/- 11 fmol/mg protein in controls (P less than 0.01). Moreover, the renal concentration of specific 1,25-(OH)2D3-binding sites of 34.6 +/- 7.1 fmol/mg protein in diabetic mice was also significantly reduced compared to the value of 63.3 +/- 5.7 fmol/mg protein in controls (P less than 0.01). There were no significant differences in the equilibrium dissociation constants (Kd) of intestinal and renal receptors between control and diabetic mice. Significant hypocalcemia was demonstrated in the diabetic mice (P less than 0.01), suggesting the development of a negative calcium balance. Diabetic mice showed a significant decrease in renal 24,25-(OH)2D3 production (P less than 0.02), whereas renal 1,25-(OH)2D3 production was significantly increased in the diabetic group (P less than 0.05) compared to the control value. It is probable from these results that the genetic/endogenous diabetes may be directly associated with the alterations of mineral homeostasis. The altered calcium and vitamin D metabolism in diabetic mice is suggested to be derived, at least in part, from the decreased number of the 1,25-(OH)2D3 receptors in both intestine and kidney in the diabetic state.
 ...
PMID:The number of 1,25-dihydroxyvitamin D3 receptors is decreased in both intestine and kidney of genetically diabetic db/db mice. 283 63


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