Biomedical subjects

Carl-David Agardh

Publications and source records attributed to Carl-David Agardh.

25 records · Page 2Linked to original sources

PubMed2002

Biological factors are more important than socio-demographic and psychosocial conditions in relation to hypertension in middle-aged women. The Women's Health in the Lund Area (WHILA) study.

The objective of this cross-sectional study was to analyse the influence of biological, socio-demographic, and psychosocial factors and current perimenopausal status on hypertension in a geographically defined population of 10,766 women aged 50-59 years, of whom 6901 attended the study. Altogether 1887 (27.3%) women had hypertension: 996 with drug treatment and 891 diagnosed at the study. In a logistic multiple regression analysis (controlled for age), drug treatment of hyperlipidaemia, family history of hypertension, waist-to-hip ratio, body mass index (BMI) increase > or = 25% during the past 25 years, S-triglycerides, S-cholesterol, education up to comprehensive school, and to upper secondary school, consumption of 84-167 g of alcohol/week, and of > or = 168 g of alcohol/week, were positively associated with hypertension, while high-density lipoprotein cholesterol and current smoking were negatively associated. A significant interaction was found between current smoking and BMI increase, with a lower risk for hypertension among smokers who had increased their BMI > or = 25%. No interaction was found between smoking and alcohol. In conclusion, hypertension was predominantly associated with biological factors, and with heredity for hypertension. Of the socio-demographic factors, only low level of education was associated with hypertension in a comprehensive analysis. Perimenopausal status showed no relation to occurrence of hypertension in the multiple regression analysis. The risk for hypertension increased with moderate and high consumption of alcohol, whereas smoking showed a decreased risk. Among women with weight gain, present smoking remained protective. Although both smoking and hypertension are established risk factors for cardiovascular disease, they seem not to be directly linked, indicating a complexity of mechanisms.

Alcohol Drinking↗

PubMed2002

Health profile of middle-aged women: The Women's Health in the Lund Area (WHILA) study.

BACKGROUND: Middle-aged women experience various health-related problems. The aim of this study was to evaluate the impacts of menopause status and hormone intervention on women's health. METHODS: In an ongoing, population-based study, 4943 women, born 1935 to 1945 and living in the Lund area of Southern Sweden, were included in this analysis. They completed a generic questionnaire pertaining to socio-demographic background and current health-related symptoms. Among the cohort, 9% of women were pre-menopausal (PM), 52% were post-menopausal without hormone replacement therapy (PMO) and 39% were current hormone replacement therapy users (PMT). RESULTS: Hot flushes and vaginal dryness were strongly related to menopausal status. The prevalence of somatic symptoms worsened progressively from the groups of PM to PMO to PMT. The most abundant complaints were headache and muscle-skeletal-joint problems. A total of 85% of women experienced psychological problems. Contrary to our expectation, a poorer profile of psychological health was found in the PMT group when compared with the PMO group. CONCLUSIONS: The high prevalence of symptoms in middle-aged women could be attributed to age, hormonal influence as well as personality.

Behavior↗

PubMedDate not supplied

Gender differences in GAD antibody-positive diabetes mellitus in relation to age at onset, C-peptide and other endocrine autoimmune diseases.

BACKGROUND: Females have an increased incidence of autoimmune diseases. However, no gender difference in the incidence of type 1 diabetes is found. The frequency of antibodies against glutamic acid decarboxylase (GADA) in diabetes mellitus depends on age at diagnosis and also gender. Several studies have shown that high GADA levels can predict future beta-cell failure and need for insulin treatment. The aim of this study was to investigate possible gender differences in relation to GADA levels, fasting plasma C-peptide levels and frequency of other autoimmune endocrine diseases in GADA-positive patients with different age at diabetes diagnosis. METHODS: GADA were screened in 4974 patients from a local diabetes registry, and plasma C-peptide was measured and a history of other autoimmune endocrine diseases was recorded. Of these patients, 822 were GADA positive and were further divided into four groups depending on the age at diagnosis of diabetes; Group 1: <20 years, Group 2: 20-39 years, Group 3: 40-59 years and Group 4: > or =60 years. RESULTS: Female patients in Group 3 had lower fasting plasma C-peptide levels (median 0.21[0.00-0-56] vs. 0.41[0.00-0.73] nmol/L, p=0.02), higher GADA levels (median 7 [4-9] vs. 5 [2-7] Arbitrary Unit (AU), p=0.0003) and higher frequency of other autoimmune endocrine diseases (22.4 vs. 5.3%, p=0.0001) than male patients. In a stepwise logistic regression analysis, diabetes duration (p<0.000001), high GADA levels (Exp (B) 3.68 CI 1.69-7.98, p=0.001) and low BMI (p=0.00002) were associated with total beta-cell failure in Group 3. CONCLUSIONS: GADA-positive female diabetic patients with an age at diagnosis between 40 and 59 years have higher GADA levels and a more severe loss of beta-cell function than male patients with the same age at diagnosis. This could be due to the effect of sex steroids and/or GnRH on the regulation of the immune system. Female patients with high GADA levels also had a high prevalence of other autoimmune endocrine diseases, especially autoimmune thyroid disease, which further emphasises the need for screening of thyroid function in female patients with high GADA levels.

Adolescent↗

PubMedDate not supplied

Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.

The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 microg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 microg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 microg dose group. GADA log levels clearly increased (P=.0002) in response to 500 microg Diamyd. The (CD4+)(CD25+)/(CD4+)(CD25-) cell ratio increased (P=.0128) at 24 weeks in the 20 microg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.

Adult↗

PubMedDate not supplied

Putative role of polymorphisms in UCP1-3 genes for diabetic nephropathy.

Increased production of reactive oxygen species (ROS) has been suggested as a cause of diabetic complications. Uncoupling proteins (UCPs) have been ascribed a role in reducing the formation of ROS, and genetic variation in genes encoding for UCPs could thus be putative candidate genes for diabetic nephropathy. To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes. We did not find any association between the different polymorphisms and diabetic nephropathy, nor did we observe any difference in AER among carriers of different UCP1-3 genotypes. We could, however, confirm the reported association between BMI and the UCP3 -55 C-->T polymorphism; patients carrying the T allele had higher BMI than patients homozygous for the C allele (26.4+/-4.2 vs. 25.3+/-4.3 kg/m(2); P=.01). We conclude that studied polymorphisms in the UCP1-3 genes do not play a major role in the development of micro- or macroalbuminuria in Scandinavian diabetic patients.

Albuminuria↗

PubMedDate not supplied

HLA-DRB1, -DQA1, and -DQB1 subtypes or ACE gene polymorphisms do not seem to be risk markers for severe retinopathy in younger Type 1 diabetic patients.

The aim of this study was to test the hypothesis that HLA-DRB1, -DQA1, and -DQB1 subgroups or angiotensin-converting enzyme (ACE) gene polymorphisms are associated with severe retinopathy in younger Type 1 diabetic patients. Twenty-four Type 1 diabetic patients who had received panretinal photocoagulation for severe nonproliferative or proliferative diabetic retinopathy were compared with 24 Type 1 diabetic patients (participating in a photographic screening program with regular fundus examinations) with no or minimal retinopathy, matched for age at onset and duration of diabetes. The HLA-DRB1-DQA1-B1 haplotype 04-03-0302 represented 22/48 (46%) in the severe and 21/48 (44%) in the no/minimal retinopathy group, respectively (n.s.). The most common genotype, 03-0501-0201/04-03-0302, occurred in 8/24 (33%) with severe and 10/24 (42%) with no/minimal retinopathy, respectively (n.s.). There were no statistical differences between patients with severe and no/minimal retinopathy whether DRB1, DQA1, or DQB1 alleles, haplotypes, or genotypes were analysed. The ACE gene polymorphism was almost identical between patients with severe and no/minimal retinopathy, and serum ACE levels did not differ. Thus, in the present study on a small group with carefully characterised diabetic retinopathy phenotypes, there was no indication that HLA-DRB1, -DQA1, and -DQB1 subtypes or ACE gene polymorphisms were associated with severe retinopathy in younger Type 1 diabetic patients.

Adult↗

PubMedDate not supplied

Bovine retinal pericytes are resistant to glucose-induced oxidative stress in vitro.

Diabetic retinopathy is a sight-threatening complication of diabetes, and loss of pericytes represents early signs of its development. We tested the hypothesis that high glucose levels may induce signs of oxidative stress in cultured bovine retinal pericytes. Pericytes were exposed to either normal (5.5 mM) or high (22 mM) glucose levels for 1, 3, and 5 days. Signs of oxidative stress were measured by expression of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase using real-time RTPCR. To elucidate the role of oxidative stress, we also measured glutathione (GSH) concentration in the cells and investigated the impact of thiol-reactive metal ions and hydrogen peroxide (H(2)O(2)) on intracellular GSH. Despite the stimulation with high glucose, thiol-reactive metal ions, or H(2)O(2), there was no clear increased expression of antioxidant enzymes or influence of GSH levels. Lipid peroxidation (malondialdehyde level) was increased in bovine aortic smooth muscle cells, but not in bovine retinal pericytes. The data indicate that pericytes do not develop oxidative stress in response to hyperglycemia. However, it is not definitively excluded that oxidative stress may occur after longer time periods of glucose stimulation.

Animals↗