Effect of amlodipine on insulin resistance & tumor necrosis factor-alpha levels in hypertensive obese type 2 diabetic patients.

BACKGROUND & OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) has been suggested to play a key role in insulin resistance (IR) in obesity and may contribute to the development of type 2 diabetes mellitus. Recently, studies are focused on the effect of antihypertensive drugs on insulin sensitivity and cytokines. We undertook this study to evaluate the effect of amlodipine, a long-acting dihydropyridine calcium channel blocker treatment on TNF-alpha, homeostasis model assessment (HOMA) IR and leptin levels in obese hypertensive type 2 diabetic patients. METHODS: Amlodipine 5-10 mg for 12 wk was given to type 2 diabetic patients in the amlodipine group. Pre- and post-treatment values of laboratory parameters in the amlodipine group were compared with those of normotensive nondiabetic obese controls. At baseline blood pressures (BP) and metabolic parameters were measured in all patients and repeated after 12 wk in the amlodipine group. RESULTS: Basal waist-to-hip ratio, systolic and diastolic BPs, fasting glucose, TNF-alpha and HOMAIR values of the amlodipine group were higher than the control group. No difference was detected in body mass index, fasting insulin, hemoglobin A1c and leptin values between groups. The systolic and diastolic BPs, fasting glucose, HOMA-IR and TNF-alpha values decreased significantly after the treatment. But, there was no correlation between percentage change in TNF-alpha and HOMA-IR. INTERPRETATION & CONCLUSION: Besides reducing BP, amlodipine seemed to improve IR and decrease TNF-alpha levels. In this context, these properties may provide additional benefits of antihypertensive drug regimens chosen for this population, but larger group interventions are needed.

Immunoglobulin subclasses and HLA alleles in immunoglobulin A deficiency.

OBJECTIVE: The term "IgA Deficiency (IgAD)" should be reserved for the individuals who do not have detectable disorders known to be associated with low IgA levels. IgG subclass deficiency or a lack of the IgG2 subclass that is specific against polysaccharide antigens, can be seen in many cases. METHODS: Forty-five patients (27 males and 18 females; mean age 8.6 years, range 6.3 to 12.8 years) with IgA deficiency who had been admitted to the Department of Pediatric Immunology in Uludag University School of Medicine, Turkey, were included in this study. Serum immunoglobulin (Ig) class and IgG subclass levels, and HLA haplotypes were prospectively determined in patients and healthy controls. RESULTS: Of the 45 patients with IgAD, 1 was found to have a low level of IgG in the serum. Serum Ig levels were also examined in the families of 22 patients. Five patients had low-normal levels of IgM, whilst one had low levels of IgA and IgG. The levels of IgG subclasses were assessed in 23 patients. One patient had a low level of IgG1; 2 had low levels of both IgG2 and IgG3, and 11 had low levels of IgG3. IgG subclass concentrations were found to be normal in control groups. HLA alleles were tested in 25 patients. An increased prevelence of HLA-A1, -B8, -B14, -DR1, -DR3, and -DR7 were previously observed in patients with IgA deficiency. In this study, HLA-A1 allel was found in 3 patients (12%), HLA-B14 in 3 patients (12%), HLA-DR1 in 10 patients (40%), HLA-DR7 in 4 patients (16%) and HLA-DR3 in 1 patient (4%). HLA-B8 allel was not found in any patient. Twenty-five children with normal IgA levels have chosen as a control group. They had HLA-DR1 (36%), HLA-DR7 (16%), HLA-B8 (8%), HLA-DR3 (16%). HLA-A1 was not found in any member of our control group. CONCLUSION: No statistically significant difference in HLA susceptibility alleles was found between patients and healthy controls. Our data suggest that there may be heterogenous HLA distribution patterns in IgA deficiency, or that HLA allel-associated tendency to IgA deficiency may be polygenic.