Short-term effects of glucagon-like peptide 1 (GLP-1) receptor agonists on fat distribution in patients with type 2 diabetes mellitus: an ultrasonography study

AIMS:Glucagon-like peptide 1 receptor agonists (GLP-1 RA) induce weight loss and reduction in adipose tissue, but the effects of GLP-1 RA on the distribution of fat deposits have been poorly investigated. METHODS: In 25 patients with type 2 diabetes (16 females and 9 males, mean age 63.5 ± 8.8 years), treated with GLP-1 RA (exenatide, n. 12; liraglutide, n.13), both before and 3 months after starting treatment, an abdominal ultrasonographic scan, with Doppler of renal arteries, and echocardiography were performed. Subcutaneous fat width (peri-umbilical and sub-xiphoid), deep fat deposits (pre-aortic, peri-renal, and epicardial), and renal resistive index (RI) were evaluated. RESULTS: GLP-1 RA induced highly significant (p < 0.001) decrease in BMI and in fat thickness at all the assessed sites, without differences between exenatide and liraglutide treatment. A slight decrease in RI (p = 0.055) was also found. The percent changes of fat thickness was different between sites (p < 0.025), and the changes in subcutaneous deposits showed no significant correlation (p = 0.064) with those of deep fat deposits. CONCLUSIONS: A short course of treatment with GLP-1 RA, besides weight loss, induces a redistribution of adipose tissue deposits, possibly contributing to a better cardiovascular risk profile in patients with type 2 diabetes mellitus

Aging related changes of circadian rhythmicity of cytotoxic lymphocyte subpopulations

<p>Abstract</p> <p>Background</p> <p>Immunosenescence is a process that affects all cell compartments of the immune system and the contribution of the immune system to healthy aging and longevity is still an open question. Lymphocyte subpopulations present different patterns of circadian variation and in the elderly alteration of circadian rhythmicity has been evidenced. The aim of our study was to analyze the dynamics of variation of specific cytotoxic lymphocyte subsets in old aged subjects.</p> <p>Methods</p> <p>Lymphocyte subpopulation analyses were performed and cortisol serum levels were measured on blood samples collected every four hours for 24 hours from fifteen healthy male young-middle aged subjects (age range 36-55 years) and fifteen healthy male old aged subjects (age range 67-79 years).</p> <p>Results</p> <p>In healthy young-middle aged subjects CD20 were higher and at 06:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16 correlated positively with γδTCR+ cells At 18:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16+ correlated positively with γδTCR+ cells and a clear circadian rhythm was validated for the time-qualified changes of CD3+, CD4+, CD20+, CD25+ and HLA-DR+ cells with acrophase during the night and for the time-qualified changes of CD8+, CD8+ bright, CD8+ dim, CD16+ and γδTCR+ cells with acrophase during the day. In old aged subjects CD25, DR+ T cells and cortisol serum levels were higher, but there was no statistically significant correlation among lymphocyte subpopulations and a clear circadian rhythm was evidenced for time-qualified changes of CD3+ and CD25+ cells with acrophase during the night and for the time-qualified changes of CD8+ cells and cortisol with acrophase during the day.</p> <p>Conclusion</p> <p>Our study has evidenced aging-related changes of correlation and circadian rhythmicity of variation of cytotoxic lymphocyte subpopulations that might play a role in the alteration of immune system function in the elderly.</p

Chronobiologic study of the GH-IGF1 axis and the ageing immune system

One of the many systems that weakens as we age is our immune system and there is a reduction in the GH-IGF1 axis activity with increasing age. In this study we evaluated the immune system and the GH-IGF1 axis function in healthy ageing. CD3, CD4, CD20, CD25, HLA-DR and GH showed acrophase during the night, whereas CD8, CD16 and TCRγδ expressing cells showed acrophase during the day. MESOR of CD3 was higher in the old aged subjects, MESOR of CD20 and CD20 values at 14:00h and at 02:00h were higher in the young middle aged subjects, MESOR of CD25 and CD25 values at 10:00 were higher in the elderly subjects, MESOR of HLA-DR was higher in the young middle aged subjects, whereas MESOR of DR+T cells and HLA-DR at 02:00h were higher in the elderly subjects, MESOR of TCRγδ bearing cells was higher in the elderly subjects, GH value at 18:00h was also higher in the elderly subjects, and MESOR of IGF1 was higher in the young middle aged subjects. There was a statistically significant difference for the acrophases of CD25, HLA-DR and IGF1. There were different and opposing correlations among lymphocyte subpopulations and GH-IGF1 axis hormones in young and middle aged subjects in comparison with old aged subjects. Linear regression evidenced a statistically significant positive trend between age and the 24h mean of CD3 and CD25 and a statistically significant negative trend between age and the 24h mean of CD20 and GH. In conclusion, ageing is associated with an altered GH and IGF1 secretion, with decreased peripheral B cell compartment, increased peripheral T cell compartment and alterations of circadian rhythmicity

Analysis of <i>MTNR1B</i> gene polymorphisms in relationship with <i>IRS2</i> gene variants, epicardial fat thickness, glucose homeostasis and cognitive performance in the elderly

<p>Genome-wide association studies pinpointed common variants in or near the <i>MTNR1B</i> gene encoding MT2 melatonin receptor to be strongly associated with fasting glucose levels. <i>IRS2</i> gene polymorphisms impact insulin resistance and epicardial fat (EF) thickness, which in turn is correlated with visceral adiposity, cognitive ability and risk for metabolic plus cardiovascular disease. We aimed to discover the interactions between <i>MTNR1B</i> and <i>IRS2</i> gene polymorphisms, insulin sensitivity, EF thickness and cognitive performance in the elderly. In 60 subjects aged 60 years and older, we evaluated five single nucleotide polymorphisms (SNPs) within the <i>MTNR1B</i> locus (rs10830962, rs4753426, rs12804291, rs10830963, rs3781638), the Gly1057Asp variant of <i>IRS2</i> gene (rs1805097), biochemical parameters, cognitive performance by the Mini Mental State Examination (MMSE) and EF thickness by transthoracic echocardiography. We found that <i>MTNR1B</i> and <i>IRS2</i> gene variants impacted EF thickness, lipid profile and glucose homeostasis. <i>IRS2</i> but not <i>MTNR1B</i> variants impacted MMSE scores. In conclusion, <i>MTNR1B</i> SNPs interact with <i>IRS2</i> gene variant, correlate with the amount of epicardial adipose tissue and impact glucose homeostasis and lipid profile influencing cardiometabolic risk.</p