Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45–65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001) effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual’s 24-hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05) of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin relative to cycle mean, or expression of subcutaneous adipose leptin gene expression, compared with lean subjects

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Major Determinants of the Carotid Intima-Media Thickness in Type 2 Diabetic Patients: Age and Body Mass Index

The present study has been designed to quantify and compare right and left carotid intima-media thicknesses (IMT) in type 2 diabetics and healthy controls. It was also intended to investigate the effects of various risk factors on the carotid IMT in these subjects. A total of 122 subjects; 70 patients with type 2 diabetes and 52 non-diabetic subjects as controls, were recruited for the study. Right and left common carotid artery stiffness indices were assessed with ultrasonography in both groups. Age, body mass index (BMI), duration of diabetes, cigarette smoking, lipid profile including lipoprotein a, Chlamydia pneumonia seropositivity, glycemic indices, fasting insulin levels, serum fibrinogen levels and presence of hypertension, coronary artery disease, degenerative complications of diabetes mellitus were all assessed in order to define their role as determinants of carotid artery IMT. The difference between the groups regarding mean carotid IMT was statistically significant for the left carotid arteries (p=0.028) and borderline significance was found for the right carotid arteries (p=0.055). Age has a very strong association with carotid IMT in diabetic patients (p<0.0001) with univariate analysis. According to the results of multivariate analysis, age and BMI were found to be the most important independent determinants of carotid TMT for both sides. When age was excluded from the model, BMI and coronary artery disease were found to have strong association with IMT on the right (p=0.0036 and 0.0249) and BMI was the only significant determinant for the left side (p=0.0025). This study shows that carotid IMT is greater in diabetic subjects compared with healthy controls. For the diabetic subjects, age, BMI and presence of coronary heart disease have a strong influence on the atherosclerotic process of the carotid arteries.WoSScopu

Chlamydia Pneumonia Seropositivity Correlates With Serum Fibrinogen And Lipoprotein A Levels: Any Role In Atherosclerosis?

The aim of the study is to determine the impact of Chlamydial seropositivity on atherosclerosis in a group of patient requiring coronary and/or carotid revascularization. A population of 30 diabetic patients (group 3) and 26 nondiabetic patients (group 2) with angiographically documented coronary and/or carotid artery disease were enrolled for the study. Volunteers from the relatives of hospital staff with no known disease (n=29; group 1) were included as the control group. Serum samples from the participants were assayed for cardiovascular risk factors including total serum cholesterol, triglyceride and lipoprotein levels, fibrinogen, Hb Al, levels and IgG titers for Chlamydia pneumonia (C. pneumonia). Chlamydial seropositivity was analysed further to determine a possible impact on atherogenesis. Serum LDL cholesterol levels revealed statistically significant difference between groups 1 and 2 (p=0.001). There was no difference between groups 2 and 3 regarding LDL cholesterol levels. There was no significant difference among the groups with respect to C. pneumonia seropositivity and the other atherosclerotic risk factors. Chlamydial seropositivity was found to be more frequent in males than in females (p=0.008). In the C. pneumonia seropositive group, serum fibrinogen and lipoprotein a levels were found to be significantly higher than the seronegative group (p=0.0001 and p=0.001, respectively). Other atherogenic risk factors were similar in the seropositive and negative groups. The causal role of Chlamydial infections in atherosclerotic plaque formation might be due to their influence on the serum fibrinogen and lipoprotein a levels.WoSScopu

GA genotype of the Arg280His polymorphism on the XRCC1 gene: Genetic susceptibility genotype in differentiated thyroid carcinomas?

Differentiated thyroid carcinomas (DTC) are the most common form of endocrine malignancies. The role of genetic variations in the development of papillary thyroid carcinoma (PTC) is approximately 60.0-70.0%. The X-ray repair cross-complementing group 1 (XRCC1) protein has an important role in DNA repair mechanisms and genomic polymorphisms of XRCC1 gene affect the function of the protein. In the present case-control study, we aimed to compare the genotype frequency distributions of XRCC1 single nucleotide polymorphisms (SNPs) in terms of the presence of other risk factors (Hashimoto’s thyroiditis, smoking, obesity, radiation exposure) in patients with thyroid nodules who had fine-needle aspiration biopsy (FNAB) and/or thyroid surgery due to thyroid cancer. The genotype frequency distributions of three common XRCC1 SNPs (Arg194Trp, Arg399Gln, Arg280His) were compared to those with DTC (n = 228), benign thyroid nodules (BTN, n = 100) and healthy controls (n = 93) in terms of certain pre defined risk factors such as the presence of Hashimoto’s thyroiditis, smoking, obesity, a family history of thyroid cancer and radiation exposure. The frequency of the GA genotype of Arg280His in DTC cases was found to be higher than in those with BTN and the healthy control group (p <0.001). The DTC group had the lowest frequency of AA genotype of Arg280His (35.5%, p <0.001). Among those with a family history of thyroid cancer, 78.9% had a GA genotype and 21.1% had the AA genotype of Arg280His (p = 0.004). The Arg280His GA genotype was more common in DTC than in cancer-free controls. The GA genotype frequency was also high in DTC cases with a family history of thyroid cancer