Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus.

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of diabetes and its complications. Arachidonic acid lipoxygenases have been intensively studied in their role in inflammation in metabolic pathways. Thus, we aimed to explore variants of lipoxygenase genes (arachidonate lipoxygenase genes) in a diabetes adult population using a case-control study design. METHODS: Study population consisted of 1285 elderly participants, 716 of whom had type 2 diabetes mellitus. The control group consisted of non-diabetes individuals with no history of diabetes history and with a glycated haemoglobin <6.5% (<48 mmol/mol)] and fasting plasma glucose levels <126 mg/dL. Blood samples were genotyped on Illumina Infinium PsychArray. Variants of ALOX5, ALOX5AP, ALOX12, ALOX15 were selected. All statistical analyses were undertaken within PLINK and SPSS packages utilising permutation analysis tests. RESULTS: Our findings showed an association of rs9669952 (odds ratio = 0.738, p = 0.013) and rs1132340 (odds ratio = 0.652, p = 0.008) in ALOX5AP and rs11239524 in ALOX5 gene with disease (odds ratio = 0.808, p = 0.038). Rs9315029 which is located near arachidonate ALOX5AP also associated with type 2 diabetes mellitus ( p = 0.025). No variant of ALOX12 and ALOX15 genes associated with disease. CONCLUSION: These results indicate a potential protective role of ALOX5AP and 5-arachidonate lipoxygenase gene in diabetes pathogenesis, indicating further the importance of the relationship between diabetes and inflammation. Larger population studies are required to replicate our findings.

Matrix Gelatinases in Atherosclerosis and Diabetic Nephropathy: Progress and Challenges.

BACKGROUND: Matrix metalloproteinases (MMPs) are zinc-dependent proteases that degrade components of the extracellular matrix (ECM). In glomerular disease, MMPs are major regulators of ECM degradation as well as structural and functional integrity in the glomerulus. In altered matrix composition diseases, glomerular damage is due to increased degradation of kidney and vessel basement membranes (BMs) by MMPs. MMP -2 and -9 are both considered as the main enzymes that degrade collagen type-IV (coll-IV), which represents the key collagenous component of ECM and constitutes the architectural structure of vessels and glomerular BM. There is growing evidence implicating MMPs in atherosclerosis as well as in cardiovascular disease (CVD) and chronic kidney disease (CKD). Specific endogenous tissue inhibitors of MMPs (TIMPs) are also implicated in CKD, CVD and diabetic nephropathy (DN). CONCLUSION: The present review discusses the role of MMPs -2 and -9 in DN, as a leading cause of endstage renal disease and as a model of the link between progressive glomerulosclerosis and MMP expression.

Left ventricular systolic and diastolic function in normotensive type 2 diabetic patients with or without autonomic neuropathy: a radionuclide ventriculography study.

We investigated the relation between diabetic autonomic neuropathy (DAN) and left ventricular (LV) function in 59 patients with type 2 diabetes mellitus (T2DM) free of coronary artery disease (CAD) or hypertension. Diabetic autonomic neuropathy was established by ≥2 abnormal autonomic nervous function tests. Left ventricular systolic and diastolic functions were assessed by resting radionuclide ventriculography. Compared with non-DAN patients (n=24), patients with DAN (n=35) had an increased adjusted atrial contribution to ventricular filling (A/V%, 30.1%±8.2% vs 26.5%±5.1%; P=.031), suggestive of diastolic dysfunction (DD). There were no differences between the 2 groups in peak filling rate, first 1/3 filling fraction, ejection fraction, cardiac output, and cardiac index. Patients with diabetic autonomic neuropathy had an increased heart rate (77.8±6.3 vs 69.3±3.3 bpm; P<.0001) and a higher rest LV workload (10,072±1165 vs 8606±1075 bpm mm Hg; P<.0001). Patients with DAN T2DM without CAD or hypertension have DD, increased A/V index, and a higher LV working load than non-DAN patients.

Aortic elastic properties are related to left ventricular diastolic function in patients with type 1 diabetes mellitus.

OBJECTIVE: The aim of the study was to evaluate left ventricular diastolic function and its relation to aortic wall stiffness in patients with type 1 diabetes mellitus without coronary artery disease or hypertension. PATIENTS: Sixty-six patients with type 1 diabetes mellitus were examined by echocardiography and divided into two groups according to the diastolic filling pattern determined by mitral annulus tissue Doppler velocities. Group A patients (n = 21) presented diastolic dysfunction with a peak early diastolic mitral annular velocity (Em)/peak late diastolic mitral annular velocity (Am) ratio <1 whereas in group B patients (n = 45) the Em/Am ratio was >1. Coronary artery disease was excluded based on normal thallium scintigraphy. Aortic stiffness index was calculated from aortic diameters measured by echocardiography, using accepted criteria. RESULTS: Aortic stiffness index differed significantly among the two groups. Significant correlations were found between parameters of left ventricular diastolic function (Em/Am, isovolumic relaxation time, deceleration time) and aortic stiffness index. Multiple stepwise linear regression analysis revealed aortic stiffness index (beta = -0.39, p = 0.001) and isovolumic relaxation time (beta = -0.46, p < 0.001) as the main predictors of Em/Am ratio. CONCLUSIONS: Aortic stiffness is increased in type 1 diabetic patients with left ventricular diastolic dysfunction. This impairment in aortic elastic properties seems to be related to parameters of diastolic function.