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The article provides information on a study that examined whether exposure to consecutive high-fat mixed meals during a 24-hour period will disclose type 2 diabetic patients' compromised metabolism and subsequent endothelial dysfunction. Plasma glucose, triglyceride, and insulin concentrations rose postprandially in patients, relative to baseline and healthy control subjects. At baseline, flow-mediated dilation was decreased in patients versus control subjects, and deteriorated postprandially in both groups

Fat accumulation in the liver or non-alcoholic fatty liver disease (NAFLD) is regarded as a key pathogenic factor and component of the metabolic syndrome. It was reported that administration of the incretin mimetic exenatide reversed hepatic steatosis in an obese mouse model. We had the opportunity to study the effect of additional exenatide administration on liver fat content in a patient with type 2 diabetes. Case report: A 59-year-old male with poorly controlled type 2 diabetes was treated with exenatide in addition to metformin monotherapy. Following 44 weeks of exenatide therapy, mean the liver fat measured by liver spectroscopy declined from 15.8% to 4.3%. This dramatic decrease in liver fat was accompanied by significant beneficial changes in several cardiovascular disease risk factors and improvement of all liver enzymes, in particular alanine aminotransferase, the most important marker of liver steatosis. Conclusion: This case report suggests that the incretin mimetic exenatide decreases hepatic fat accumulation and may play a role in the future treatment of NAFLD, and the associated insulin resistance and cardiovascular risk factors in an ever-growing high-risk population. [ABSTRACT FROM AUTHOR]

Background: Peroxisome proliferator-activated receptor (PPAR) agonists may have favorable outcomes on non-alcoholic fatty liver disease. This study serves as proof of concept to evaluate whether dual PPAR-α/γ agonists improve non-invasive tests of liver steatosis and fibrosis. Methods: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled, multi-center trial comprising 7226 patients with type 2 diabetes mellitus and recent coronary artery disease randomized to receive aleglitazar, a PPAR-α/γ agonists, or placebo for two years. Main outcomes were change in non-invasive tests for liver steatosis and fibrosis: Liver Fat Score (LFS), Liver Accumulation Product (LAP), Fibrosis-4 (FIB-4), and NAFLD Fibrosis Score (NFS). Results: LFS, LAP and FIB-4 decreased upon treatment, whereas scores in the placebo group remained the same or increased (P<0.001). NFS responded differently but remained consistently lower than placebo. In the treatment group more participants shifted to a lower FIB-4 and NFS category, or improved in respect to the LAP cut-off values compared to the placebo group (P<0.001 for FIB-4 and LAP, P<0.004 for NFS). LFS had a low discriminative power in this study. Conclusion: This post-hoc analysis showed improvement of non-invasive tests of liver steatosis and fibrosis after starting dual PPAR-α/γ agonist treatment, adding to the evidence that this pathway has potential in non-alcoholic fatty liver disease treatment. [ABSTRACT FROM AUTHOR]

In insulin resistant states, increased lipolysis in adipose tissue and unsuppressed hepatic VLDL-triglyceride output lead to a high exposure of non-adipose tissues to lipids. Experimental and autopsy data indicate that fatty infiltration of pancreatic islets may also contribute to β-cell dysfunction, but whether this phenomenon occurs in humans in vivo is unknown. Using proton magnetic resonance spectroscopy and oral glucose tolerance tests, we studied the association of pancreatic lipid accumulation in vivo and various aspects of β-cell function in 12 insulin-naïve type 2 diabetic and 24 age- and BMI-matched non-diabetic males. Patients versus controls had higher HbA1c, fasting plasma glucose, insulin and triglyceride levels, lower HDL-C, but similar waist circumference. Median (interquartile range) pancreatic fat content in patients was 20.4(13.4-43.6) and 9.7(7.0-20.2)% in controls (P=0.032). Pancreatic fat correlated negatively with β-cell function parameters, including insulinogenic index adjusted for insulin resistance, early phase insulin secretion, β-cell glucose sensitivity, rate sensitivity (all P<0.05), but not potentiation. The interaction of pancreatic fat with the diabetic state significantly affected the association. Separate analyses showed a significant association of pancreatic fat with β-cell dysfunction in the non-diabetic group only (all P<0.01), suggesting that once diabetes occurs, factors additional to pancreatic fat may account for further β-cell function decline. In controls, the association of pancreatic fat and β-cell dysfunction remained significant after correction for BMI, fasting plasma glucose and triglycerides (P=0.006). These findings indicate that pancreatic lipid content may contribute to β-cell dysfunction and possibly to the subsequent development of type 2 diabetes in susceptible humans. [ABSTRACT FROM AUTHOR]

Abstract: Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n =27) and without albuminuria (NA, n =48) and controls (CO, n =28). MMP-8 and -9 levels were highest in UA patients (P <0.01). Of UA patients, 93% had at least one MMP increased, compared to 78% of NA patients and 46% of CO (P =0.001). Age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c and renal function were determinants of MMP-8 and -9 (P <0.05). In summary, MMP-8 and -9 are highest in T2DM UA patients. MMP-9, showed the strongest associations with clinical parameters related to DN. [Copyright &y& Elsevier]

Type 2 diabetes (DM2) and the metabolic syndrome (MetS) are conditions associated with a high risk of coronary artery disease (CAD) and congestive heart failure (CHF). Although CAD contributes to diastolic dysfunction and left ventricular (LV) stiffness, the interaction between CAD, DM2 and the MetS, is largely unknown. We studied the impact of CAD, DM2 and the MetS on LV function and stiffness in patients who underwent a diagnostic coronary angiography. Sixty patients (n=22 with and n=21 without the MetS and n=17 with DM2; n=38 males were studied. Only subjects with LV ejection fraction >40% were included to avoid the confounding of post myocardial infarction remodeling. CAD severity was determined according to the number of the vessels with >50% stenosis. Thus, 26 patients had no CAD, 14 had 1, 9 had 2, 11 had 3 vessel disease. Hemodynamic and echocardiographic data were collected and combined to calculate percent LV wall thickening (LVWT%), a measure of systolic function, as well as LV end-diastolic wall thickness (LVWTed) and myocardial stiffness modulus, both variables of diastolic function. LVWT% did not differ among groups. DM2 subjects and those with the MetS had higher LVWTed than controls (P=0.019), but LV stiffness was not increased. Patients with vs those without CAD had higher LVWTed (P=0.022) and lower LVWT% (P=0.031). A trend for increased LV stiffness in CAD patients was observed (P=0.158). LV stiffness worsened according to the number of vessels involved (P=0.044). Multivariate analyses revealed CAD as an independent determinant of LV stiffness, after correction for age, gender and fasting glucose, in patients with MetS and DM2 (P=0.002), but not in controls (P=0.895). In conclusion, increased LVWTed was observed in subjects with the MetS and DM2, vs controls, and in patients with relative to those without CAD. We show that the contribution of CAD to LV stiffness depends on the presence of dysmetabolic conditions including the MetS and DM2. These findings implicate that strategies aiming early detection and treatment of CAD in people with MetS and DM2 may prevent future development of CHF. [ABSTRACT FROM AUTHOR]