Association study between chromosome 10q26.11 and obesity among Swedish men

OBJECTIVE: Proximal chromosome 10q26 was recently linked to waist/hip ratio in European and African-American families. The objective was to investigate whether genomic variation in chromosome 10q26.11 reflects variation in obesity-related clinical parameters in a Swedish population. DESIGN: Genetic association study of single-nucleotide polymorphisms (SNPs) in chromosome 10q26.11 and obesity-related clinical parameters was performed. Obesity was defined as body mass index (BMI) > or = 30 kg/m2. SUBJECTS: Swedish Caucasians comprising 276 obese and 480 nonobese men, 313 obese and 494 nonobese women, 177 obese and 163 nonobese patients with type 2 diabetes mellitus (T2DM), and 106 obese and 201 nonobese subjects with impaired glucose tolerance (IGT) patients. MEASUREMENTS: Genotypes of 11 SNPs at chromosome 10q26.11, and various obesity-related clinical parameters. RESULTS: Homozygosity of a common haplotype constructed by three SNPs, rs2185937, rs1797 and hCV1402327, covering an interval of 2.7 kb, was suggested to confer an increased risk for obesity of 1.5 among men (P = 0.043). The C allele frequency and homozygous genotype frequency of the rs1797 tended to be higher among obese compared to among nonobese men (P = 0.017 and 0.020, respectively). The distribution of BMI and diastolic blood pressure was higher among those with the C/C genotype (P = 0.022 and 0.0061, respectively). The obese and the nonobese groups were homogeneous over BMI subgroups with regard to rs1797 risk genotype distribution. There was no tendency for association between rs1797 and obesity among neither women nor T2DM nor IGT patients. CONCLUSION: We show support for association between proximal chromosome 10q26.11 and obesity among Swedish men but not women through the analysis of a haplotype encompassing 2.7 kb.     

Skeletal changes in type-2 diabetic Goto-Kakizaki rats

We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age- and sex-matched non-diabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment.     

Day-care attendance and increased risk for respiratory and allergic symptoms in preschool age

BACKGROUND: The reported impact of day-care attendance on respiratory and atopic symptoms has varied between studies from different countries. Regarding to the 'hygiene-hypothesis', day-care attendance may lead to less sensitization later in life, but the question still is whether day-care attendance and subsequent exposure to more frequent early infections is a risk or a protection against future allergic disease or asthma (atopic and nonatopic). METHODS: A cross-sectional postal questionnaire was replied by parents of 10,851 children, aged 1-6 years, in the year 2000 in a Swedish region (DBH-phase 1). The questionnaire focused on respiratory and atopic symptoms, the home environment and information on day care of the children. RESULTS: Children in day care were reported to have more symptoms than children in home care: adjusted odds ratio (AOR) for wheezing last 12 months, AOR 1.33 (CI 95%: 1.12-1.58), cough at night apart from colds last 12 months AOR 1.56 (CI: 1.17-2.07), doctor diagnosed asthma AOR 1.23 (CI: 0.88-1.71), rhinitis last 12 months AOR 1.15 (CI: 0.92-1.44), doctor diagnosed hay fever AOR 1.75 (CI: 0.94-3.23), eczema last 12 months, AOR 1.49 (CI: 1.24-1.79), allergic reactions to foods, AOR 1.27 (CI: 1.07-1.52), >6 colds last 12 months of 2.57 (CI: 2.12-3.12) and ear infection ever AOR 2.14 (CI: 1.87-2.45). The increased risks were mainly seen and reached significance in the youngest group of children, aged 1-4 years. Adjusting and stratification for the number of airway infections last year did not change the risk associated with day-care attendance for allergic diseases. CONCLUSIONS: Attending day care was associated with an increased risk of symptoms related to airways infections as well with eczema and allergic reactions to food. No sign of protection from day-care attendance for allergic diseases was found up to 6 years of age. Multiple airway infections and day-care attendance were found to be independently associated with asthma and allergic symptoms.     

Does the clinical outcome of hepatitis C infection vary with the infecting hepatitis C virus type?

Whether differences in the natural history of hepatitis C virus (HCV) can be explained by differences in the infecting HCV type is unknown. The aim of this study was to investigate whether the HCV type might influence the clinical outcome of infection. Study serum samples were assembled from 749 individuals enrolled into the UK HCV National Register from which data on clinical outcomes were extracted. HCV-RNA-positive specimens were genotyped and HCV-RNA-negative specimens serotyped. Logistic regression analysis was used to investigate the independent effect of HCV type on viral clearance by comparing patients who were HCV RNA negative (n = 86) with those who were HCV RNA positive (n = 508). The same method was used to investigate whether HCV type was associated with histological stage of liver disease. The prevalence of HCV type 1 among those who cleared infection was 69% and among those who remained HCV RNA positive was 51%: Type 1 infections were more likely to be HCV RNA negative than non-1 types (OR 0.47, 95% CI 0.29-0.78, P = 0.003). Type 1 infections were also more likely to be associated with histological stage scores above the median when compared with non-1 types (OR 2.03, 95% CI 1.07-3.83, P = 0.03). In conclusion, HCV type 1 infection was more often HCV RNA negative, suggesting that spontaneous clearance may occur more commonly with this type. Among the RNA-positive infections, type 1 infection may be more aggressive than types 2/3.     

Rapid inhibitory effects of corticosterone on calcium influx in rat dorsal root ganglion neurons

Corticosterone may nongenomically affect cell functions in addition to its well-characterized effects on gene expression. The purpose of this study is to examine if corticosterone has a rapid nongenomic effect on excitability of dorsal root ganglion neurons by using patch-clamp and single-cell Ca(2+) microfluometry techniques. The results show that corticosterone has a dose-dependent rapid inhibitory effect on the voltage-dependent calcium currents in dorsal root ganglion neurons. Moreover, corticosterone inhibits [Ca(2+)](i) elevation induced by 50 mM high K(+) within just 3 s. The inhibitory effects of corticosterone on the voltage-dependent calcium current and high K(+)-induced calcium influx diminish after adding protein kinase C inhibitor or pretreatment with pertussis toxin for 24 h. Our results demonstrate an nongenomic effect of corticosterone on the excitability of dorsal root ganglion neurons and the effect is mediated through a putative pertussis toxin-sensitive G-protein-coupled receptor and activation of protein kinase C.     

Effects of dexamethasone,diclofenac, or placebo on the inflammatory response after cataract surgery

AIM: To compare the inflammatory response after phacoemulsification and intraocular lens (IOL) implantation using postoperative treatment with dexamethasone, diclofenac, or placebo. METHODS: A prospective, randomised, controlled double masked study including 180 patients enrolled for cataract surgery. The patients were 64-85 years old and had no eye disease other than cataract. After phacoemulsification and IOL implantation the patients were randomised to topical treatment with dexamethasone phosphate 0.1% (group I), diclofenac sodium 0.1% (group II), or placebo (saline 0.9%) (group III). The drops were administered four times daily during the first week and twice daily during the second, third, and fourth weeks. The inflammatory reaction in the anterior chamber was measured with laser flare photometry preoperatively and 1, 3, and 8 days, 2 and 4 weeks, 2 and 6 months, and 1, 2, and 4 years postoperatively. Inflammatory symptoms were registered. Biomicroscopy and visual acuity determinations were performed. The rate of Nd:YAG laser posterior capsulotomies after 2 and 4 years was determined. RESULTS: After 3 and 8 days (p <0.0001), 2 weeks (p <0.0001), and 1 month (p = 0.0013) median flare was highest in group III. There were no significant differences between group I and II. Inflammatory symptoms and striate keratopathy were more common in group III. CONCLUSION: Dexamethasone and diclofenac were equally effective in reducing postoperative inflammation after phacoemulsification and IOL implantation in eyes with no other disease than cataract. Both substances were more effective than placebo.     

Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women

OBJECTIVES: The association between coffee consumption, type 2 diabetes and impaired glucose tolerance was examined. In addition, indicators of insulin sensitivity and beta-cell function according to homeostasis model assessment were studied in relation to coffee consumption. DESIGN: Population-based cross-sectional study. SETTING AND SUBJECTS: The study comprised 7949 healthy Swedish subjects aged 35-56 years residing within five municipalities of Stockholm. An oral glucose tolerance test identified 55 men and 52 women with previously undiagnosed type 2 diabetes and 172 men and 167 women with impaired glucose tolerance. Information about coffee consumption and other factors was obtained by questionnaire. RESULTS: The relative risks (adjusted for potential confounders) of type 2 diabetes and impaired glucose tolerance when drinking >/=5 cups of coffee per day compared with /=5 cups day(-1)) was inversely associated with insulin resistance. In addition, in those with type 2 diabetes and in women (not in men) with impaired glucose tolerance high coffee consumption was inversely associated with low beta-cell function. In women, but not obviously in men, with normal glucose tolerance, coffee consumption was associated with a reduced risk of insulin resistance. CONCLUSIONS: The results of this study indicated that high consumers of coffee have a reduced risk of type 2 diabetes and impaired glucose tolerance. The beneficial effects may involve both improved insulin sensitivity and enhanced insulin response.     

Enhanced leukocyte–platelet cross-talk in Type 1 diabetes mellitus: relationship to microangiopathy

Summary. Background: Platelets and leukocytes may influence each others' function, i.e. platelet–leukocyte cross‐talk. Diabetes mellitus (DM) is associated with platelet and leukocyte dysfunction. Objective: To evaluate platelet–leukocyte cross‐talk, and if this might contribute to platelet and leukocyte dysfunction and microangiopathy in DM patients. Patients and methods: We evaluated platelet and leukocyte function, and cross‐talk between these cells in Type 1 DM patients without (n = 19) and with (n = 20) microangiopathy, and healthy subjects (n = 27), using whole blood flow cytometry. Platelet–leukocyte cross‐talk was studied in hirudinized whole blood incubated at 37 °C with stirring. Results: Basal single platelet P‐selectin and leukocyte CD11b expression were similar in DM patients and healthy subjects, whilst circulating platelet–leukocyte aggregates and plasma elastase levels were elevated in DM patients. The thromboxane A₂ analog U46619 (3 × 10^?7 m ) induced more marked increases of platelet P‐selectin expression and platelet–leukocyte aggregation in DM patients than in healthy subjects. The leukocyte‐specific agonist N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) (10^?7 m ) induced more marked CD11b expression in DM patients with microangiopathy, compared with healthy subjects. Platelet–leukocyte cross‐talk induced by U46619 (10^?6 m ) showed no difference between DM patients and healthy subjects. fMLP (10^?6 m ) evoked marked leukocyte activation, which subsequently caused mild platelet P‐selectin expression. This leukocyte–platelet cross‐talk was more pronounced in DM patients than in healthy subjects. Furthermore, enhanced leukocyte–platelet cross‐talk was correlated to platelet hyperreactivity among DM patients with microangiopathy only. Conclusions: Type 1 DM is associated with platelet and leukocyte hyperactivity, and enhanced leukocyte–platelet cross‐talk, which may contribute to platelet hyperactivity and the microvascular complications seen in Type 1 DM.