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

We have carried out studies on cultured human fibroblasts in an attempt to trace the origins of age-dependent disorders to the cellular and molecular levels. Three interrelated areas are discussed. First, skin donors with diabetes mellitus (a disease complex that features inappropriate hyperglycemia) produce cultured fibroblasts with a moderate reduction in growth capacity, while two inherited disorders of inappropriate hyperglycemia and premature aging, progeria and Werner syndrome, yield fibroblast cultures with more severely impaired growth capacity. Second, there is a decreased response of progeria level and donor age; evidence is presented that this defective hormone responsiveness in aging cells may reside at the hormone receptor on the surface membrane, the cyclic AMP system, the intracellular enzymatic machinery, or all of these sites. Third, tissue factor, a procoagulant that activates the extrinsic clotting mechanism, is more abundant in cells from the premature aging syndromes of progeria and Werner syndrome. Fibroblast aging in vitro may help to explain various concomitants of normal aging and diabetes mellitus including cell dropout, impairment of hormone responsiveness, and increased atherothrombosis.
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PMID:In vitro studies of age-associated diseases. 42 66

Werner's syndrome is a genetic disease characterized by premature aging and is often associated with glucose intolerance due to insulin resistance. The clinical manifestations in this syndrome are preferentially expressed in the face and acral regions without apparent involvement of the trunk. We compared insulin receptor binding and amino acid uptake of fibroblasts derived from the forearm that had sclerodermoid features, and from the abdomen that was apparently normal in a patient with Werner's syndrome. In normal controls, specific insulin binding was not different in forearm and abdomen-derived fibroblasts (10.72 +/- 2.11%, 10.40 +/- 1.27%, respectively). In the patient, however, specific insulin binding was reduced in the fibroblasts derived from the forearm compared with those derived from the abdomen (3.55%, 8.16%, respectively). Scatchard analysis revealed that the reduction in insulin binding of the forearm fibroblasts from the patient was due to a reduction in receptor number with no change in receptor affinity. The dose-response curve for insulin of alpha-aminoisobutyric acid (AIB) uptake is shifted to the right in the fibroblasts derived from the acral area. The results show that in a patient with Werner's syndrome, regional differences occur in fibroblast insulin receptor binding and function. This suggests early phenotypic expression of the genetic abnormality of insulin receptor function in these patients.
Diabetes Res Clin Pract 1992 Feb
PMID:Regional differences in insulin receptor function in Werner's syndrome. 156 26

Werner's syndrome (adult progeria) is a rare autosomal recessive condition characterized mainly by a characteristic habitus (short stature, light body weight) scleroderma like changes of the limbs and premature aging. Chronic leg ulcers appears in about fifty per cent of the patients. These ulcers can be related to the combination of mechanical factors on atrophic subcutaneous tissue and skin of the feet and leg associated with early arteriosclerosis (20%) and diabetes mellitus (60%).
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PMID:[Leg ulcers in Werner's syndrome. Report of one case]. 179 75

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)
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PMID:Geriatric nutrition. 218 27

Diabetes mellitus (DM), associated with very subtle disorders, affects, either directly or indirectly, various functions of the reproductive system. Adequate, regular, and timely therapy may prevent or delay these disorders. The T synthesis disorder is caused by molecular changes at the level of Leydig cells and may lead to other disorders in all target organs and tissues. The close correlation between Leydig and Sertoli cells function, i.e., between spermatogenesis and second sex glands function, results in certain anomalies in diabetic patients' spermiograms. Parallel lesions associated with DM, through CNS (hypothalamus-hypophysis), and endocrine profile are indirectly intensified or induced by these disorders, which reflect dysfunction of homeostatic balance in carbohydrate metabolism. Sexual dysfunction in all its forms (reduced erection, impotence, and other libido dissociations) is an accompanying phenomenon of the diabetic disease. However, manifestations of these disorders are related to the regulation of carbohydrate metabolism and to the duration of disease. The duration of disease is not necessarily correlated with sexual dysfunction. Even carbohydrate metabolism remains within normal range in addition to other lesions, diabetes leads gradually but progressively to premature aging of body cells.
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PMID:Diabetes mellitus/male infertility. 228 51

The extent of glycation in pieces of human aorta was estimated by determining the content of furosine, which is derived from fructose-lysine through acid hydrolysis. Glycation of human aorta was found to increase with advancing age. A significant positive correlation was found between the degree of atherosclerosis and the furosine level in the aorta in subjects over 60 years of age. Furthermore, the furosine level in the aortae of diabetic patients was significantly higher than that in normal subjects of the same age. These results suggest not only that glycation in the aorta may increase with aging and with the development of arteriosclerosis, but also that diabetes may be related as well to premature aging as to arteriosclerosis.
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PMID:Age- and diabetes-accelerated glycation in the human aorta. 250 75

Down's syndrome has been associated with organ-specific autoimmunity and 'premature aging'. We studied 27 individuals with Down's syndrome (all trisomy 21, no translocations aged 0.5 to 50 years). Subjects were not preselected for autoimmunity. Six subjects had a history of hypothyroidism and three additional subjects had anti-microsomal antibodies (euthyroid). Three subjects had insulin-dependent diabetes mellitus and one additional subject had islet cell autoantibodies (non-diabetic). The percentage Ia (Dr) positive T cells exceeded the normal range in 7/26 (27%). The percent CD4+ and CD8+ T cells were not significantly different from control. A subgroup of Down's syndrome subjects (less than age 10) had a premature increase in the percentage of 3G5+ (age-related) T cells. Normal individuals express a similar percentage of 3G5+ T cells at age 50 to 70 years. The presence of T-cell activation and 'premature T-cell aging' may predispose Down's syndrome subjects to organ-specific autoimmunity and age-related disorders.
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PMID:Trisomy 21 (Down's syndrome): autoimmunity, aging and monoclonal antibody-defined T-cell abnormalities. 252 34

Diabetes mellitus and hypertension are both common diseases, especially with an increasingly aged population. Hypertension accelerates the development of diabetic retinopathy, nephropathy, and peripheral vascular disease in the diabetic patient. Diabetes represents a type of premature aging and hypertension in the diabetic patient is characterized by many of the same pathophysiologic properties seen in the elderly hypertensive patient.
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PMID:Hypertension and diabetes. 305 60

Normal nondiabetic homozygous and heterozygous littermates of db/db diabetes-prone mice (seven/group) were fed a 5% solution of glucose as their sole source of liquid for 10 wk. Controls (seven/group) drank tap water, and both groups received stock diet ad libitum. Body weights, tail lengths, food and fluid consumption were recorded throughout the study, and plasma and urine glucose were measured during wk 10. The total caloric intake, including the glucose solution drunk by some of the mice, was not significantly different among the four groups. No differences in plasma or urine glucose were detected. Total-body dry weight, water and lipid were measured, and pancreata were analyzed for beta-cell polyploidy by a combination of Feulgen cytophotometry and nuclear size analysis. The percentage of polyploid beta-cells was significantly higher in the animals that drank glucose than in those that drank water and was independent of both genotype and growth indices attributable to genotype. The greater polyploidization was interpreted as reflecting premature aging of the beta-cell population. It was hypothesized that such glucose-induced premature aging in animals with a genetically restricted potential for beta-cell proliferation could contribute to the precipitation of overt diabetes.
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PMID:Excess glucose intake induces accelerated beta-cell polyploidization in normal mice: a possible deleterious effect. 388 72

Age and diabetes-related changes in the extent of non-enzymatic glycosylation of two anatomically distinct human basement membranes were examined. The amount of glucose in ketoamine linkage to glomerular basement membrane, measured by the thiobarbituric acid reaction, correlated positively and significantly with age. For analysis of lens capsule basement membrane, adsorption to agarose-linked phenylboronate was used. The ability of this resin to completely discriminate non-glycosylated from glycosylated residues was first documented by separating synthetic preparations of radioactive glucitol-lysine and glucitol-hydroxylysine, the glucosylamines formed with non-enzymatic glycosylation of collagen, from the respective free amino acids by affinity chromatography on and batch adsorption to phenylboronate. The extent of non-enzymatic glycosylation of lens capsule basement membranes correlated with age in both non-diabetic and diabetic samples, and the slopes of the lines for age versus glycosylation were similar in both groups. The calculated line for diabetic specimens, however, was displaced about 15 years to the left, compatible with premature aging. The results indicate that non-enzymatic glycosylation can be accurately assessed in minute amounts of tissue by phenylboronate adsorption, and provide evidence that human basement membrane is subject to increased glycosylation with aging and diabetes.
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PMID:Age-related changes in non-enzymatic glycosylation of human basement membranes. 642 73


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