Sorbitol accumulation in rats kept on diabetic condition for short and prolonged periods.
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AIM: To study the influence of the course of diabetes, aging, and glycemia on the sorbitol accumulation in diabetic rats. METHODS: Streptozocin (Str) diabetic rats were obtained by Str i.v. (35 mg.kg-1). Glycemia and sorbitol levels from sciatic nerve and lens were measured after 1 d, 2, 5, and 8 months of diabetes. Sorbitol concentrations in serum, heart, diaphragm, small intestine, and kidney after 8 months of diabetes were measured. RESULTS: Diabetic rats after Str injection showed hyperglycemia (> 1.7 g.L-1), hyperphagia, polyuria, polydipsia, and loss of body weight. Sorbitol levels in lens and sciatic nerve increased in normal and diabetic rats; the increase was higher in diabetic rats. No relationship was shown between glycemia and sorbitol levels. An increased sorbitol level after 8 months of diabetes was found in small intestine and kidney. CONCLUSION: The sorbitol levels increased in lens and sciatic nerve with aging and this process was accelerated by diabetes. (+info)
The effects of age on human venous responsiveness to neuropeptide Y.
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AIMS: Neuropeptide Y (NPY) is a sympathetic neurotransmitter released with noradrenaline during sympathetic stimulation. Ageing has been shown to be associated with a reduction in alpha2 and beta-adrenoceptor mediated responses in veins, but it is not known whether NPY responsiveness is also altered with increasing age. METHODS: Using a dorsal hand vein technique, we examined NPY receptor responsiveness in 24 normal, healthy subjects (20-72 years; 10 males, 14 females). Graded infusions of NPY (25-2000 pmol min(-1)) were administered (5 min at each dose) into a dorsal hand vein. Venous distension at 45 mmHg was measured at 3-5 min of each infusion. Dose-response curves to NPY were constructed and the peak venoconstriction was calculated. RESULTS: Dose-dependent venoconstriction was seen in all but one subject. The peak venoconstriction observed with NPY was significantly and negatively correlated with the age of the normal subjects (r=-0.63, P<0.01). When subjects were ranked from youngest to oldest and divided into tertiles, (20-40 years, n = 8; 41-55 years, n = 8; 56-72 years, n = 8), mean dose-response curves were different with the oldest tertile being significantly less responsive (P<0.05). The peak venoconstriction observed (% of control) was 65.1+/-7.0, 46.5+/-9.4, and 24.4+/-4.8%, respectively. The oldest tertile had a significantly decreased peak venoconstriction compared with the youngest tertile (P<0.01). Infusion of NPY into a dorsal hand vein had no systemic effects on heart rate or blood pressure in any of the subjects studied. CONCLUSIONS: Hand vein responsiveness to exogenously infused NPY in normal subjects is decreased as age increases. The reduction of NPY-receptor-mediated responses with age may influence sympathetic nervous system control of the venous system with advancing age. (+info)
Variation by body mass index and age in waist-to-hip ratio associations with glycemic status in an aboriginal population at risk for type 2 diabetes in British Columbia, Canada.
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BACKGROUND: It is unclear whether obesity and age modify or confound relations between abdominal adiposity and metabolic risk factors for type 2 diabetes. OBJECTIVE: Our objective was assess the consistency of relations between abdominal adiposity and glycemic variables across discrete categories of obesity and age. DESIGN: We performed a stratified analysis of prevalence data from a rural screening initiative in British Columbia, Canada. Subjects were Salishan Indians, all healthy relatives of individuals with type 2 diabetes [n = 151; age: 18-80 y; body mass index (BMI, in kg/m2): 17.0-48.2]. We measured waist-to-hip ratio (WHR) (2 categories); insulin, glycated hemoglobin (Hb A1c), and 2-h glucose concentrations (2 categories); and BMI (4 categories). BMI and age-specific odds ratios (ORs) and 95% CIs were calculated. RESULTS: WHR-glycemic variable relations were not consistent across BMI and age strata. Risks associated with high WHR were: for persons with BMIs from 25 to 29, elevated insulin (OR: 6.71; 95% CI: 1.41, 34.11) and Hb A1c (OR: 16.23; 95% CI: 2.04, 101.73) concentrations; for persons aged 18-34 y, elevated insulin concentrations [OR: indeterminate (+infinity); 95% CI: 1.89, +infinity]; and, for persons aged 35-49 y, elevated Hb A1c (OR: +infinity; 95% CI: 3.17, +infinity) and 2-h glucose (OR: 9.15; 95% CI: 1.74, 59.91) concentrations. CONCLUSIONS: WHR discriminates risk of type 2 diabetes in overweight but not obese individuals. Abdominal adiposity is associated with elevated insulin concentrations in younger age groups and with impaired glucose control in middle-aged groups, suggesting metabolic staging by age on a continuum from insulin resistance to impaired glucose tolerance. (+info)
Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population.
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BACKGROUND: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy. OBJECTIVE: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area. DESIGN: We performed observational analyses of baseline and 2-4-mo follow-up data collected in a study designed to test the feasibility of conducting a large-scale clinical trial of vitamin supplements by mail. The study population consisted of 151 women and 109 men with a median age of 64 y. At baseline, each participant completed a food-frequency questionnaire. At follow-up, fasting serum tHcy was measured. RESULTS: In multivariable linear regression and generalized linear models, there was an independent, inverse dose-response relation between dietary protein and In tHcy (P = 0.002) and a positive, significant dose-response relation between coffee consumption and In tHcy (P for trend = 0.01). Other significant predictors of In tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B vitamins (inverse; P = 0.03). In stratified analyses restricted to persons receiving standard multivitamin therapy, the association of 1n tHcy with dietary protein and coffee persisted. CONCLUSIONS: These results support the hypothesis that increased protein intake and decreased coffee consumption may reduce tHcy and potentially prevent atherosclerotic cardiovascular disease and other disease outcomes. (+info)
Age-related hearing loss, vitamin B-12, and folate in elderly women.
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BACKGROUND: Hearing impairment is 1 of the 4 most prevalent chronic conditions in the elderly. However, the biological basis of age-related hearing loss is unknown. OBJECTIVE: The objective was to test the hypothesis that age-related hearing loss may be associated with poor vitamin B-12 and folate status. DESIGN: A thorough audiometric assessment was conducted in 55 healthy women aged 60-71 y. Hearing function was determined by the average of pure-tone air conduction thresholds at 0.5, 1, 2, and 4 kHz and was categorized into 2 groups for logistic regression analyses: normal hearing (<20 dB hearing level; n = 44) and impaired hearing (> or = 20 dB hearing level; n = 11). RESULTS: Mean age was the same (65 y) for the normal hearing and impaired hearing groups. Pure-tone averages were inversely correlated with serum vitamin B-12 (r = -0.58, P = 0.0001) and red cell folate (r = -0.37, P = 0.01). Women with impaired hearing had 38% lower serum vitamin B-12 (236 compared with 380 pmol/L, respectively, P = 0.008) and 31% lower red cell folate (425 compared with 619 nmol/L, respectively, P = 0.02) than women with normal hearing. Among participants who did not take supplements containing vitamin B-12 or folate, women with impaired hearing had 48% lower serum vitamin B-12 (156 compared with 302 pmol/L, respectively, P = 0.0007) and 43% lower red cell folate (288 compared with 502 nmol/L, respectively, P = 0.001) than women with normal hearing. CONCLUSION: Poor vitamin B-12 and folate status may be associated with age-related auditory dysfunction. (+info)
Mitochondria in organismal aging and degeneration.
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Several lines of experimentation support the view that the genetic, biochemical and bioenergetic functions of somatic mitochondria deteriorate during normal aging. Deletion mutations of the mitochondrial genome accumulate exponentially with age in nerve and muscle tissue of humans and multiple other species. In muscle, a tissue that undergoes age-related fiber loss and atrophy in humans, there is an exponential rise in the number of cytochrome-oxidase-deficient fibers, which is first detectable in the fourth decile of age. Most biochemical studies of animal mitochondrial activity indicate a decline in electron transport activity with age, as well as decreased bioenergetic capacity with age, as measured by mitochondrial membrane potential. Mitochondrial mutations may be both the result of mitochondrial oxidative stress, and cells bearing pure populations of pathogenic mitochondrial mutations are sensitized to oxidant stress. Oxidant stress to mitochondria is known to induce the mitochondrial permeability transition, which has recently been implicated in the release of cytochrome c and the initiation of apoptosis. Thus several lines of evidence support a contribution of mitochondrial dysfunction to the phenotypic changes associated with aging. (+info)
Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study.
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The temporal development of autoantibodies was studied in 1,353 offspring of parents with type 1 diabetes. Islet cell antibodies (ICAs) and autoantibodies to insulin (IAAs), glutamic acid decarboxylase, and IA-2 were measured at birth, 9 months, 2 years, and 5 years of age. At birth, no offspring had islet autoimmunity other than maternally acquired antibodies, which were shown to influence antibody prevalence up to age 6 months. Antibodies detected thereafter were likely to represent a true de novo production, since prevalences were the same for offspring from mothers and fathers with diabetes, antibodies detected at 9 months were almost always confirmed in the 2-year sample and were associated with an increased likelihood of having or developing other antibodies. By 2 years of age, autoantibodies appeared in 11% of offspring, 3.5% having more than one autoantibody. IAAs were detected most frequently, and few had autoantibodies in the absence of IAAs. In 23 offspring with multiple islet autoantibodies, IAAs preceded other antibodies in 10 cases and were first detected concurrently with other antibodies in 12 and after detection of other antibodies in 1. Development of additional antibodies and changes in levels, including decline of IAAs at older age, was frequent. Nine children, all with IAAs and ICAs, developed diabetes. Overall cumulative risk for disease by 5 years of age was 1.8% (95% CI 0.2-3.4) and was 50% (95% CI 19-81) for offspring with more than one autoantibody in their 2-year sample. Autoimmunity associated with childhood diabetes is an early event and a dynamic process. Presence of IAAs is a consistent feature of this autoimmunity, and IAA detection can identify children at risk. (+info)
Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes.
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The autosomal dominant neurological syndrome of Huntington's disease has been modeled in transgenic mice by the expression of a portion of the human huntingtin gene together with 140 CAG repeats (the R6/2 strain). The mice develop progressive chorea with onset at approximately 9 weeks of age and with death at approximately 13 weeks. Associated symptoms include weight loss and polyuria in the absence of eating or drinking deficits. We have found that these mice have insulin-responsive diabetes. Fasting glucose was 211 + 19 mg/dl in R6/2 mice compared with 93 + 5 mg/dl in C57/B6 controls (n = 12, both groups; P < 0.01). Administration of insulin intraperitoneally led to a reduction in blood glucose. At 12.5 weeks, animals were killed and pancreas weighed and analyzed for insulin and glucagon. Pancreatic mass in R6/2 mice was the same as controls, and islets appeared normal in morphology without lymphocytic infiltration. Immunohistochemical staining showed dramatic reductions in glucagon in the alpha-cells and in insulin in the beta-cells. Direct tissue assays showed glucagon and insulin content were reduced to only 10 and 15% of controls, respectively. Diabetes has been reported as being more common in Huntington's disease and other triplet repeat disorders. The R6/2 mouse should prove useful for elucidating the mechanism of diabetes in these genetic diseases. (+info)