An analysis of epidemiological data in HLA-typed diabetic children

Summary To clarify the heterogeneity of Type 1 (insulin-dependent) diabetes mellitus, differences between patients with different HLA risk antigens were investigated with regard to sex, age at diagnosis, season of year and calendar year at diagnosis of the disease. The study consisted of 293 HLA-typed patients from the Department of Paediatrics, University of Oulu, Oulu, Finland. HLA-Dw2 was extremely rare among diabetic patients, whereas Dw3 and Dw4 were associated with increased risk in this as in other series. Male patients more often had the HLA-A1 antigen than females. On comparison of the Dw3 positive patients, boys more frequently had the combination A1,B8 than girls. A1,B8-positive patients were more often diagnosed during the warm months, in the late summer and autumn. Patients with both Dw3 and Dw4 were younger at diagnosis when compared with the rest of the patients. The results support the concept of heterogeneity in the pathogenesis of Type 1 diabetes associated with HLA-linked genetic determinants.     

Accumulation of lipid in muscular arteries of short-term diabetic rats

Summary Lipid accumulation in muscular (pulmonary, coronary and tibial) arteries and elastic (aorta and pulmonary) arteries of streptozotocin diabetic (65 mg/kg) rats was studied with an electron microscope. Arterial tissue specimens taken 4 days after the induction of diabetes showed lipid deposits in smooth muscle cells in the muscular arteries of 9 out of 24 diabetic rats, but in none of the 17 control rats. Histochemically the lipid was identified as triacylglycerol. Lipid accumulation was not seen in the elastic arteries of either diabetic or control rats. The diabetic animals with lipid deposits had slightly but significantly higher plasma glucose concentrations (p<0.02), higher non-esterified fatty acids levels (p<0.01), and lower concentrations of plasma insulin (p<0.02) than those without arterial deposits. The amount of lipid deposited in the arteries was closely related to the plasma non-esterified fatty acid level, which was in the ranges 0.8–1.1 mmol/l in diabetic rats without deposits, and 1.1–2.4 mmol/l in those with deposits. The findings suggest that lipid accumulation in smooth muscle cells of muscular arteries during acute diabetes could result from the high plasma non-esterified fatty acid concentrations.     

Exercise-induced proteinuria in children and adolescents with Type 1 (insulin dependent) diabetes

Summary The urinary excretion of albumin and -₂microglubulin was measured by radioimmunoassay in 64 children and adolescents with Type 1 (insulin dependent) diabetes and in 68 non-diabetic subjects aged from 9 to 19 years. At rest the albumin excretion of the diabetic subjects did not differ from that of the non-diabetic children and adolescents but during exercise the albumin excretion was significantly higher in children and adolescents with Type 1 diabetes (p<0.02). The excretion rate of ₂-microglobulin in diabetic subjects did not differ from that of the healthy subjects. Both at rest and during exercise the albumin excretion rate was highest in those diabetics with poorest metabolic control of their disease.     

Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study

BRCA1 and BRCA2 screening in women at high‐risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population‐based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA‐binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. © 2010 Wiley‐Liss, Inc.     

Thylakoids suppress appetite by increasing cholecystokinin resulting in lower food intake and body weight in high‐fat fed mice

Thylakoids are membranes isolated from plant chloroplasts which have previously been shown to inhibit pancreatic lipase/colipase catalysed hydrolysis of fat in vitro and induce short‐term satiety in vivo. The purpose of the present study was to examine if dietary supplementation of thylakoids could affect food intake and body weight during long‐term feeding in mice. Female apolipoprotein E‐deficient mice were fed a high‐fat diet containing 41% of fat by energy with and without thylakoids for 100 days. Mice fed the thylakoid‐enriched diet had suppressed food intake, body weight gain and body fat compared with the high‐fat fed control mice. Reduced serum glucose, serum triglyceride and serum free fatty acid levels were found in the thylakoid‐treated animals. The satiety hormone cholecystokinin was elevated, suggesting this hormone mediates satiety. Leptin levels were reduced, reflecting a decreased fat mass. There was no sign of desensitization in the animals treated with thylakoids. The results suggest that thylakoids are useful to suppress appetite and body weight gain when supplemented to a high‐fat food during long‐term feeding. Copyright © 2009 John Wiley & Sons, Ltd.     

Diet,cow's milk protein antibodies and the risk of IDDM in Finnish children

Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-date-and sex-matched population-based control children in the nationwide Childhood Diabetes in Finland study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - BLG betalactoglobulin - BSA bovine serum albumin - ICA islet cell antibodies - IAA insulin autoantibodies - OR odds ratio - CI confidence interval     

Behavioral goal assessment in patients with persistent musculoskeletal pain

Identification and achievement of behavioral goals is an important issue in pain rehabilitation. For this dual purpose, we developed a patient-specific clinical tool—the Patient Goal Priority Questionnaire (PGPQ). Using the PGPQ, this study identifies patients' behavioral goals for physical therapy (PT) in a primary health care sample of patients with persistent musculoskeletal pain. In addition, this study examines the concurrent validity of the PGPQ in relation to a generic measure of disability, the Pain Disability Index (PDI). In all, 197 subjects participated in the study. The behavioral goals differed among the patients, comprehending several everyday activities and behaviors, and thus an individualized and behavioral focus was relevant for these patients. The PGPQ was negatively and moderately correlated with the PDI, indicating patient-specific properties of the new instrument. An elaborated version of the PGPQ can serve (a) as a clinical tool for identification of the patient's priorities of behavioral goals for PT, (b) as a clinical tool for collaborative formative evaluation during treatment, and (c) as a complementary measure in research for assessment of clinically significant changes related to behavioral performance.     

Work ability is influenced by kinesiophobia among patients with persistent pain

The purpose of this study was to investigate how kinesiophobia fluctuates in patients over a four weeks multimodal rehabilitation program and to study the relationship between work ability and kinesiophobia. The study included 112 patients (94 women, 18 men). Measurements were made before, directly after, 2 months after, and 12 months after the program. The level of work ability was rated by the patients on a scale from 0% to 100%, and kinesiophobia was measured by the Swedish version of the Tampa Scale for Kinesiophobia (TSK-SV). Kinesiophobia decreased between the start of the multimodal rehabilitation program and the follow-up periods. Work ability increased over time, but not between baseline and the 2-month follow-up. Decreases in the TSK-SV score between baseline and the 2-month follow-up were related to the increased probability of improved work ability at the 12-month follow-up. In conclusion, a decrease in kinesiophobia seems to be related to increased work ability of patients participating in a 4-week multimodal rehabilitation program.