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Biomedical subjects

E Hägg

Publications and source records attributed to E Hägg.

At least 19 recordsLinked to original sources
PubMed2004

Association between insulin resistance and GAD65-autoantibody levels--a pilot study in an adult non-diabetic population.

The aim of this pilot study was to investigate any association between insulin resistance (IR) and serum levels of autoantibodies against the glutamic acid decarboxylase (GAD65Ab) among adult non-diabetic subjects. Based on calculations of IR using the IR homeostasis model in a Swedish adult non-diabetic population (n = 756) participating in the WHO MONICA-study, an insulin sensitive group (n = 54, M/F:27/27) and an insulin resistant group (n = 46 M/F:24/22) were identified. Serum from the subjects were analysed for the presence of GAD65Ab. There was no significant difference in GAD65Ab levels between the groups. However, there was a correlation between IR and serum GAD65Ab within the insulin sensitive group (Spearman rho 0.4, p < 0.01). Our observation could indicate that IR could serve as an initiator or a progression factor in the autoimmune process in subjects predisposed to autoimmunity. This finding will be further investigated in a larger study including subjects with a continuum of IR.

Adult↗
PubMed2003

High GAD65 autoantibody levels in nondiabetic adults are associated with HLA but not with CTLA-4 or INS VNTR.

OBJECTIVES: To explore the relationship between genetic background and antibody levels in a nondiabetic population. We evaluated if high levels of autoantibodies against the 65 kDa isoform of glutamic acid decarboxylase (GAD65Ab), were associated with high-risk genes, i.e. HLA, CTLA-4 and INS VNTR genes. DESIGN AND SUBJECTS: Seventy-five (M/F 39/36) subjects exceeding the 95th percentile of GAD65 autoantibody index and 75 age and sex matched subjects below the 95th percentile, randomly selected amongst participants in the Västerbotten Intervention Programme. METHODS: The GAD65 Ab were measured in a radioligand-binding assay. HLA class II typing was performed by an oligoblot hybridization method. CTLA-4 repeat length was analysed and divided into short forms and long forms. Class I and class III alleles of INS VNTR were detected. Differences in distribution were tested by Pearson chi-square with Yates correction. Odds ratios (OR) were used to compare groups calculated with Cochran's and Mantel-Haenszel statistics. RESULTS: The DQB1*0201-DQA1*0501-DRB1*03 haplotype was increased in subjects with high GAD65Ab levels (P = 0.04). This increase seemed to be explained by a difference in haplotype frequencies amongst men (P = 0.01). Calculating OR showed a significant association between the DQB1*0201-DQA1*0501-DRB1*03 haplotype and elevated levels of GAD65Ab in all subjects (OR 2.2, 95% CI 1.02-4.9) as well as in men (OR 4.6, 95% CI 1.3-15.9). There was no association between high levels of GAD65Ab and either INS VNTR or CTLA-4 polymorphisms. CONCLUSION: Our study suggests that adult males with the DQB1*0201-DQA1*0501-DRB1*03 haplotype tend to develop high GAD65Ab titres. As none of these subjects have developed diabetes these data suggest that HLA may be important in GAD65Ab formation but that additional factors are required for the progression to overt type 1 diabetes.

Abatacept↗
PubMed2001

Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population.

OBJECTIVE: Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. DESIGN: A population-based follow-up cohort study. SETTING: Participants visited the primary health care centre in Lycksele, Sweden in 1988-92. PARTICIPANTS: A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow-up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main outcome measurements. A clinically diagnosed diabetes at follow-up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies. RESULTS: At follow-up, 42/2278 (1.8%, 95% CI 1.2-2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow-up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3-18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8-12.6) in the fourth quartile of 2-h plasma glucose (>7.5 mmol L(-1)) and 7.2 (95% CI 4.8-11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L(-1)). CONCLUSION: Islet cell autoantibodies did not predict diabetes at follow-up. BMI measured at base line was as effective as 2-h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.

Adult↗
PubMed2000

Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease.

Although a specific GH deficiency (GHD) syndrome in the adult and the response to GH replacement therapy are well recognized, there are few data available on the effect of GH replacement therapy in elderly GH-deficient patients. We studied the effect of GH therapy on body composition and bone mineral density measured by dual energy x-ray absorptiometry, markers for bone metabolism, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) in 31 patients (6 women and 25 men; aged 60-79 yr; mean, 68 yr) with multiple pituitary hormone deficiencies. The GH response to arginine or insulin was below 3 microg/L (9 mU/L) in all subjects. They were randomized to GH (Humatrope, Eli Lilly & Co.) or placebo for 6 months, followed by 12 months of open treatment. The dose was 0.05 IU/kg x week for 1 month, and after that it was 0.1 IU/kg x week divided into daily sc injections (0.75-1.25 IU/day). There were no changes in any of the measured variables during placebo treatment. GH treatment normalized serum IGF-I in a majority of the patients and increased IGFBP-3 and -5 as well as IGFBP-4 and IGF-II to values within normal range. Lean body mass was increased, and the increase at 6 and 12 months correlated with the increase in IGF-I (r = 0.46; P = 0.010 and r = 0.54, respectively; P = 0.003). GH treatment caused a modest, but highly significant, reduction of total body fat. Mean bone mineral density was not different from that in healthy subjects of the same age and did not change during the observation period. Markers for bone formation (bone-specific alkaline phosphatase activity, osteocalcin, and procollagen I carboxyl-terminal peptide in serum) increased within the normal range, and levels were sustained throughout the study. The bone resorption marker (pyridinoline in urine) was significantly elevated for 12 months. Side-effects were mild, mostly attributed to fluid retention. In two patients with normal glucose tolerance at the start of the study, pathological glucose tolerance occurred in one patient and was impaired in one. In conclusion, elderly patients with GHD respond to replacement therapy in a similar manner as younger subjects, with an improvement in body composition and an increase in markers for bone metabolism. Side-effects are few, and elderly GHD patients can be offered treatment. As long-term risks are unknown, GH doses should be titrated to keep IGF-I within the age-related physiological range.

Adenoma↗
PubMed1999

Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index.

AIMS/HYPOTHESIS: Our aims were to investigate the concentrations and prevalence of autoantibodies against the Mr 65.000 isoform of glutamate decarboxylase (GAD65) and the tyrosine phosphatase-like protein (IA-2) in adults and to test the hypothesis that GAD65 and IA-2 autoantibodies in a regional population are related to abnormal oral glucose tolerance. METHODS: We analysed serum from 2157 Swedish subjects aged either 30, 40, 50 or 60 years old who, in 1988-1992, participated in the Västerbotten County Health Project and were subjected to the World Health Organisation (WHO) standard oral glucose tolerance test at entry into the study. RESULTS: We found 23 of 2157 (1.1%) and 17 of 2152 (0.8%) subjects exceeded the 99th centile of GAD65 autoantibody index and IA-2 autoantibody index, respectively. In 18 subjects with diabetic oral glucose tolerance test, GAD65 autoantibody concentrations were higher than in those with normal oral glucose tolerance test (p = 0.02). Subjects with IGT (n = 185) [corrected] and diabetes (n = 18), i.e. abnormal OGTT (n = 203) [corrected], had higher GAD65Ab [corrected] index compared with those with normal OGTT (p = 0.026) [corrected]. A stepwise multiple logistic regression test showed that the odds ratios for subjects in the highest BMI group to exceed the 95th or 99th GAD65 autoantibody centile were 3.6 (CI 1.4-8.9) and 17.6 (CI 2.6-121.6), respectively. CONCLUSION/INTERPRETATION: GAD65 and IA-2 autoantibodies, are associated with impaired or diabetic glucose tolerance in an adult regional population. This observation together with the association between GAD65 autoantibody concentrations and body mass index indicate a possible relation between islet autoimmunity and beta-cell function abnormalities with obesity and insulin resistance.

Adult↗
PubMed1999

Magnesium therapy in type 1 diabetes. A double blind study concerning the effects on kidney function and serum lipid levels.

To test the hypothesis that magnesium depletion might be of importance for the development of vascular complications in diabetes mellitus we performed a randomized, double-blind, placebo-controlled study during 12 months with 20-30 mmol/day of oral magnesium hydroxide in 28 type 1 diabetic patients. Urinary albumin excretion, Cr-EDTA-clearance and certain blood cardiovascular risk factors were measured. At the end of the study there were no significant differences of these parameters between the two groups, except that serum triglyceride values increased in three magnesium treated patients who either showed an increase in blood glycosylated hemoglobin values or body weight during the study.

Adult↗
PubMed1997

Aberrant V(H) gene utilization in patients with established insulin dependent diabetes mellitus.

We have compared the B-lymphocyte repertoire in seven IDDM patients with 12 healthy controls by examining the variable heavy (V(H)) gene expression. The V(H) gene representation in the pool of pokeweed mitogen (PWM) stimulated, immunocompetent B cells and in the pool of naturally activated plasma cells (actual repertoire) was analysed by RNA-RNA in situ hybridization. Differences between IDDM patients and normal controls in the relative expression of several V(H) gene families were observed. In IDDM patients, the V(H)3 was significantly underrepresented in the PWM stimulated repertoire. In the actual B cell repertoire the V(H)5 clones were underrepresented among diabetic patients. Moreover, the altered distribution of V(H) gene usage between the PWM stimulated repertoire and the actual repertoire observed in normal controls was found to be less pronounced in the IDDM patients. This observation suggests a defect in the V-gene directed cellular selection occurring between resting, immunocompetent B cells and naturally activated plasma cells. The possible implication of the observed aberrations in the B cell selection process for the pathogenesis of autoimmunity is discussed.

Adult↗
PubMed1994

Prediction of caries in 1 1/2-year-old children.

The aim was to test the predictive ability of defined levels of dietary and oral hygiene habits and also mutans streptococci and lactobacilli in saliva, separately and in combinations, in 1 1/2-year-old children. The population consisted of 181 children, who were investigated with respect to the above factors together with general health, use of fluoride in tablets and/or toothpaste, gingival condition and caries prevalence. Initially, 99% of the subjects were caries-free as against 72% at the age of 3 years, with a mean of 0.8 ds. Using data for sensitivity and specificity the predictive values for positive (PV+) and negative (PV-) tests were calculated for different levels and combinations of variables. A dividing line between high and low caries risk that combined high sensitivity and high specificity could not be established for any variable or combination of variables. High sensitivity was noted with diet as the predictor, high specificity with oral hygiene or occurrence of mutans streptococci. Lactobacilli were excluded as they were found in only 6 children. A two-step computation with mutans streptococci as second predictor improved the ability to single out children with caries at the age of 3 years. Subgrouping and analyses of the material as regards use of fluoride did not influence the results. To sum up, prediction at the age of 1 1/2 years, in a population with a low caries prevalence, was not successful with the variables used in this study.

DMF Index↗
PubMed1993

The prognostic value of admission blood pressure in patients with acute stroke.

BACKGROUND AND PURPOSE: Patients with acute stroke are often found to have high blood pressures at hospital admission. Previous studies have shown variable results regarding the prognostic value of high blood pressure in acute stroke. The aim of this study was to investigate the prognostic value of admission blood pressure in a population-based sample of patients with acute stroke. METHODS: Eighty-five patients with intracerebral hemorrhage and 831 with ischemic disease were included in the study. The relations between admission blood pressure and 30-day mortality were studied by logistic regression analyses. RESULTS: High blood pressure in patients with impaired consciousness on hospital admission was significantly related to 30-day mortality in patients with intracerebral hemorrhage (P = .037) and in patients with ischemic disease (P < .0001). In patients without impaired consciousness, high blood pressure at time of admission was not related to increased mortality at 30 days. CONCLUSIONS: High admission blood pressure in alert stroke patients was not related to increased mortality. Stroke patients with impaired consciousness showed higher mortality rates with increasing blood pressure. However, this does not provide a basis for recommending antihypertensive therapy for such patients.

Aged↗
PubMed1993

Influence of smoking and snuff use on electrolytes, adrenal and calcium regulating hormones.

Little is known about the effects of snuff use on health. We have investigated electrolyte levels, adrenocortical and calcium regulating hormones in three groups of healthy young men, including 18 non-tobacco users, 21 snuff users and 19 smokers with similar age and body mass index. Smoking and snuff use was positively associated with alcohol and coffee consumption and inversely related to physical activity. Compared to non-tobacco users, smokers had significantly increased levels of serum sodium and magnesium, plasma calcitonin, urinary cortisol and potassium levels and decreased serum sex hormone-binding globulin as well as serum and urinary creatinine values. However, only decreased sexual hormone-binding globulin and urinary creatinine and increased serum phosphate and urinary potassium levels were seen in snuff users. Among tobacco users we noted that smokers differed from snuff users in that they had higher serum sodium (1.4 mmol/l, p < 0.01), plasma calcitonin (3.3 pmol/l, p < 0.05) and urinary cortisol (41 nmol/24 h, p < 0.05) but lower serum creatinine (5.8 mumol/l, p < 0.01). We conclude that chronic snuff use appears to have less influence on hormone and electrolyte balance than does smoking, and that some of the abnormalities seen in smokers do not seem to be mediated by nicotine.

Adrenal Cortex↗
PubMed1993

Microangiography--a sensitive method for studying experimental diabetic nephropathy.

Microangiographic and conventional histopathologic investigations of the kidney were compared in 15 alloxan diabetic and 7 nondiabetic control rats. Contrary to the relatively sparse histologic lesions, microangiography disclosed advanced vascular abnormalities, including arteriolar aneurysms, which increased with the duration of diabetes. It is concluded that microangiography is a sensitive and suitable method for studying the development of microvascular lesions of the kidney in experimental diabetes.

Alloxan↗
PubMed1992

Screening of patients with hereditary spastic paraparesis and Addison's disease for adrenoleukodystrophy/adrenomyeloneuropathy.

X-linked adrenoleukodystrophy/adrenomyeloneuropathy presents a wide variation of clinical manifestations and may mimic several diseases. A screening investigation by measuring plasma saturated very long-chain fatty acids was performed in two groups of patients. Among six patients with hereditary spastic paraparesis one woman was detected to be a heterozygous gene carrier. However, in a group of eleven adult men with idiopathic Addison's disease the plasma concentrations of very long-chain fatty acids were all within normal limits. We conclude that X-linked adrenoleukodystrophy and symptomatic heterozygous females should be considered in cases of progressive spastic paraparesis.

Addison Disease↗
PubMed1991

Catecholamine excretion in old age.

Catecholamine excretion was studied in two groups of nonhospitalized subjects, 60 and 80 years of age, N = 35 and 29, respectively. Urinary 24h dopamine excretion exhibited an age-related decline (p = 0.001). There was a sex difference for dopamine excretion; men had higher excretion levels (p = 0.04). Twenty-four-hour excretion of epinephrine and norepinephrine was slightly higher in 60- than in 80-year-old individuals (NS). Smoking was associated with a considerable increase in epinephrine (p = 0.001) and norepinephrine (p = 0.04) excretion. Body mass index was negatively correlated to epinephrine excretion (r = -0.27; p less than 0.05). When analyzed with a multi-way analysis of variance with analysis of covariance, significant influences of age on dopamine excretion, of creatinine clearance on dopamine and norepinephrine excretion, and of smoking on epinephrine excretion were seen. Thus, factors such as age, gender, body mass, kidney function and smoking habits considerably influence catecholamine excretion in elderly people.

Aged↗