Pro- and anti-inflammatory cytokines in latent autoimmune diabetes in adults, type 1 and type 2 diabetes patients: Action LADA 4

Aims/hypothesis

Systemic pro- and anti-inflammatory cytokines are associated with both type 1 and type 2 diabetes, while their role in latent autoimmune diabetes in adults (LADA) is unclear. Therefore, we compared cytokine concentrations in patients with LADA, type 1 or type 2 diabetes and healthy individuals to test the hypothesis that differences of cytokine concentrations between all groups are attributable to diabetes type and BMI.

Methods

The pro-inflammatory cytokines IL-6 and TNF-??, and the anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and IL-10 were measured in 90 participants with type 1 diabetes, 61 with LADA, 465 with type 2 diabetes and 41 control participants using multiple regression models adjusted for BMI, sex, age, blood pressure and diabetes duration.

Results

Patients with type 2 diabetes had higher concentrations of systemic IL-1RA, IL-6 and TNF-?? cytokines than patients with either LADA or type 1 diabetes (p?<?0.0001 for all differences). Cytokine concentrations in controls were lower than those in all diabetes types (p?<?0.04). Increased BMI was positively associated with higher systemic cytokine concentrations in all diabetes types (p?<?0.0001). Despite the association of cytokines with anthropometric data, differences between diabetes forms persisted also after adjusting analysis for the confounders BMI, age, sex, disease duration and blood pressure (p?<?0.04).

Conclusions/interpretation

Although body mass associates positively with pro- and anti-inflammatory cytokine levels, patients with type 2 diabetes have higher cytokine levels independent of the prevailing BMI. LADA and type 1 diabetes could not be distinguished by systemic cytokines.     

Social contexts and HIV vulnerabilities among South Asian women in the greater Toronto area: Examining social norms

We explored how social norms interact with beliefs and social structures (power relations, emotional relations, and gendered division of labor) to influence the experiences of South Asian women with HIV in Canada. The first author conducted semi-structured interviews, and identified five themes using thematic analysis: connection to community/religious institutions, family honor, and restrained/prohibited discussion of sexuality. These norms reproduce hegemonic masculinity; constrain women's social, relational, and economic power; and elevate HIV vulnerability. We present findings to challenge hegemonic masculinity at the international level, and of developing strategies to address both interfamily gender-based violence and racism faced by the South Asians in Canada.     

Otx2-Genetically Modified Retinal Pigment Epithelial Cells Rescue Photoreceptors after Transplantation

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The imbalance between osteoprotegerin and cathepsin K in the serum of patients with longstanding rheumatoid arthritis

Osteoprotegerin (OPG) and soluble receptor activator of NF-kappa B ligand (sRANKL) together regulate the bone metabolism among other cytokines, whereby cathepsin K has a potent collagen-degrading activity. An imbalance of this system may be partly responsible for the skeletal complications of RA. Expanding on a previous study, we investigated the relationship between OPG, sRANKL and cathepsin K levels in the serum of patients with longstanding RA. We measured serum levels of OPG, sRANKL and cathepsin K of 100 patients with active, longstanding RA. We detected elevated serum levels of cathepsin K (median 54.8 pmol/l) and OPG (median 4.8 pmol/l), but normal sRANKL levels (median 0.2 pmol/l). Cathepsin K did not show a correlation with the overexpressed OPG (P = 0.64) and sRANKL (P = 0.81). The radiological destruction correlates significantly with cathepsin K (P = 0.004) and OPG (P = 0.007). We speculate that the increased levels of OPG are effective in compensating the action of sRANKL, but do not directly prevent bone degradation, as reflected by the elevated serum levels of cathepsin K.     

Effects of acute hyperglycaemia on cardiac function: an echocardiographic study of monozygotic twins

BACKGROUND: A major cause of morbidity in type I diabetes is congestive heart failure due predominantly to left ventricular diastolic dysfunction. The mechanism of diastolic dysfunction remains unknown and does not relate to blood pressure, microvascular complications and glycated haemoglobin. Hyperglycaemia is the hallmark of diabetes and is a potential determinant of left ventricular diastolic dysfunction. OBJECTIVE: To determine whether acute hyperglycaemia can induce changes in left ventricular diastolic function in normal subjects similar to those observed in insulin-dependent diabetes mellitus (IDDM). DESIGN: Cross-sectional study. SETTING: London teaching hospital. SUBJECTS: Sixteen twins from eight identical twin pairs discordant for IDDM (age 18-38 years, five male) were studied; none had a history or evidence of myocardial ischaemia, valvular or primary heart muscle disease, systemic hypertension or nephropathy. INTERVENTIONS: Non-diabetic twins underwent a hyperglycaemic clamp at 10 mmol/l. MAIN OUTCOME MEASURES: Doppler echocardiography was performed in basal condition in identical twin pairs discordant for IDDM and repeated in the non-diabetic twins during hyperglycaemia. Blood glucose, insulin and catecholamines were measured at baseline and during hyperglycaemia. RESULTS: Transmitral Doppler E/A velocity ratio was significantly lower in diabetic than non-diabetic twins at baseline (1.44 (0.38) vs. 1.51 (0.19), P<0.05). Glucose infusion in the non-diabetic twins resulted in an increase in their E/A ratio (1.51 (0.19) vs. 1.82 (0. 47), P<0.05) due to an increase in E velocity (68 (12) to 64.7 (10. 7), P<0.05) and a decrease in the peak A velocity (42.7 (3.85) to 38. 0 (4.1), P<0.05). No significant changes were observed in peak E velocity or isovolumic relaxation time in the non-diabetic twins between baseline and hyperglycaemia. CONCLUSIONS: The alterations in left ventricular diastolic function induced by acute hyperglycaemia and consequent increase in plasma catecholamines do not mimic those demonstrated in IDDM patients.     

Binding of the receptor for 1,25-dihydroxyvitamin D3 to the 5'-flanking region of the bovine parathyroid hormone gene

Receptors for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) were prepared from bovine parathyroid glands and incubated with fragments of DNA of the 5'-flanking region of the bovine parathyroid hormone (PTH) gene covering 1700 base pairs (bp) upstream of the initiation site. In filter binding assays, incubation of the DNA fragment spanning -700 to +50 bp with 200 micrograms cytosolic protein gave 288 +/- 63% (mean +/- S.D.) of binding in the absence of protein. In contrast, there was no significant reaction with the -1350 to -700 bp fragment, nor was there binding of the receptor to a fragment of DNA covering the coding region of the PTH gene. Substitution of bovine serum albumin for the receptor preparation did not induce binding to the -700 to +50 bp fragment. The receptor-binding site was further defined to -700 to -100 bp as deletion of the -100 to +50 bp did not reduce receptor binding. Reaction of receptors further purified by sucrose density ultracentrifugation with a monoclonal antibody in immunoblots revealed a single species with a molecular mass of approximately 50,000 Da, which was absent in preparations of cos-1 cells. Autoradiography following incubation of receptors immobilized on nitrocellulose filters with the -700 to +50 bp fragment indicated a single reactive band coincident with the band in the immunoblot. The DNA fragment did not bind to filters containing preparations of cos-1 cells. Extraction of the receptors in the presence or absence of 1,25-(OH)2D3 (4 nmol/l) or the presence of KCl (150 mmol/l) in the incubation medium had no significant effect on DNA binding to the protein in this assay. (ABSTRACT TRUNCATED AT 250 WORDS)     

Cutting Balloon and Stenting of a Stenosis at the Origin of the Left Internal Thoracic Artery

Catheterization was performed in a 58-year-old female with chest pain, which exposed a high-grade stenosis of the ostium of the left internal thoracic artery. Bypass had been completed three years earlier. Successful percutaneous intervention was performed utilizing a cutting balloon and a stent.