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PCsK9 and carbohydrate metabolism:A double-edged sword

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World Journal of Diabetes 2017年第7期8卷 311-316页

作者： Theodosios D Filippatos sebastian Filippas-Ntekouan Eleni Pappa Thalia Panagiotopoulou Vasilios Tsimihodimos moses s elisaf Department of Internal Medicine School of MedicineUniversity of Ioannina45110 IoanninaGreece

Proprotein convertase subtilisin/kexin type 9(PCsK9) plays a paramount role in the degradation of lowdensity lipoprotein(LDL) receptors(LDLR) on the hepatic cells surface and subsequently affects LDL particles catabolism and LDL cholesterol(LDL-c) levels. The anti-PCsK9 monoclonal antibodies lead to substantial decrease of LDL-c concentration. PCsK9(which is also expressed in pancreatic delta-cells) can decrease LDLR and subsequently decrease cholesterol accumulation in pancreatic beta-cells, which impairs glucose metabolism and reduces insulin secretion. Thus, a possible adverse effect of PCsK9 inhibitors on carbohydrate metabolism may be expected by this mechanism, which has been supported by the mendelian studies results. On the other hand, clinical data have suggested a detrimental association of PCsK9 with glucose metabolism. so, the inhibition of PCsK9 may be seen as a double-edged sword regarding carbohydrate metabolism. Completed clinical trials have not shown a detrimental effect of PCsK9 inhibitors on diabetes risk, but their short-term duration does not allow definite conclusions.

关键词： Proprotein convertase subtilisin/kexin type 9 Diabetes Carbohydrate metabolism Low-density lipoprotein Proprotein convertase subtilisin/kexin type 9 inhibitors

High density lipoproteins and type 2 diabetes:Emerging concepts in their relationship

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World Journal of Experimental Medicine 2014年第1期4卷 1-6页

作者： Michael s Kostapanos moses s elisaf Department of Internal Medicine School of Medicine University of Ioannina45110 IoanninaGreece

Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.

关键词： Type 2 diabetes High density lipoproteins Insulin secretion βcells Paraoxonase-1

Effects of glucagon-like peptide-1 receptor agonists on renal function

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World Journal of Diabetes 2013年第5期4卷 190-201页

作者： Theodosios D Filippatos moses s elisaf Department of Internal Medicine School of MedicineUniversity of Ioannina

Glucagon-like peptide-1(GLP-1)receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus.A number of case reports show an association of GLP-1receptor agonists,mainly exenatide,with the development of acute kidney *** present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function,their use in subjects with chronic renal failure and their possible association with acute kidney *** on the current evidence,exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal *** is not eliminated by renal or hepatic mechanisms,but it should be used with caution since there are only limited data in patients with renal or hepatic *** is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering ***,there is evidence that GLP-1 receptor agonists influence water and electrolyte *** effects may represent new ways to improve or even prevent diabetic nephropathy.

关键词： Glucagon-like peptide 1 Glucagon-like peptide 1 receptor agonists Exenatide Liraglutide Kidney Renal impairment Diabetic nephropathy Electrolytes

Antihypertensive drugs and glucose metabolism

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World Journal of Cardiology 2014年第7期6卷 517-530页

作者： Christos V Rizos moses s elisaf Department of Internal Medicine School of MedicineUniversity of Ioannina

Hypertension plays a major role in the development and progression of micro-and macrovascular ***,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin *** a result the need for a comprehensive management of hypertensive patients is ***,the various antihypertensive drug categories have different effects on glucose ***,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose *** channel blockers(CCBs)have an overall neutral effect on glucose ***,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose *** the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose *** note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose *** adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective *** a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

关键词： Hypertension Glucose metabolism Antihypertensive drugs

Combination drug treatment in obese diabetic patients

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World Journal of Diabetes 2010年第1期1卷 8-11页

作者： Theodosios D Filippatos moses s elisaf Department of Internal Medicine University of Ioannina

Drug combinations that include antiobesity drugs(such as orlistat and sibutramine) and target cardiovascular disease(CVD) risk factors may be a good approach to patients with type 2 diabetes and/or metabolic syndrome(Mets).Our group has investigated the orlistat-fenofibrate combination treatment in obese patients with Mets and the orlistat-ezetimibe and the sibutramine-antihypertensive combination treatment in obese patients with hyperlipidaemia with promising results in CVD risk factor *** these studies,the combination treatment significantly improved the lipid and lipoprotein profile,the carbohydrate metabolism parameters and many other variables playing a role in the atherosclerotic *** studies give pro m ising results but double-blind,randomized trials examining the effects of such multif actorial treatment in hard CVD endpoints in diabet ic or Mets patients are missing.

关键词： Diabetes Metabolic syndrome Orlistat sibutramine Fenofibrate Ezetimibe Weight loss

severe hyperkalemia following blood transfusions:Is there a link?

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World Journal of Nephrology 2017年第1期6卷 53-56页

作者： Christos V Rizos Haralampos J Milionis moses s elisaf Department of Internal Medicine Medical SchoolUniversity of Ioannina

Patients with gastrointestinal bleeding often require large volume blood transfusion. Among the various side effects of blood transfusion,the increase of potassium levels is a serious one which is often overlooked. We report a case of severe hyperkalemia in a patient with gastric bleeding after large volume transfusion of packed red blood cells. The patient had hyperkalemia at baseline associated with his receiving medication as well as acute renal failure following hypovolemia. The baseline hyperkalemia was further aggravated after massive transfusions of packed red blood cells in a short period of time. The associated pathogenetic mechanisms resulting in the increase of potassium levels are presented. A number of risk factors which increase the risk of hyperkalemia after blood transfusion are discussed. Moreover,appropriate management strategies for the prevention of blood transfusion associated hyperkalemia are also presented. Physicians should always keep in mind the possibility of hyperkalemia in cases of blood transfusion.

关键词：胃肠道出血患者治疗方法临床分析

Rationale,design and baseline patient characteristics of the optimal type 2 diabetes management including benchmarking and standard treatment study in Greece

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World Journal of Diabetes 2014年第1期5卷 76-83页

作者： Michael s Kostapanos Vasilis Tsimihodimos moses s elisaf Emmanouil Tzouvelekis Nikos Nikas Department of Internal Medicine School of MedicineUniversity of Ioannina Medical Department

AIM:To describe baseline data of the optimal type2 diabetes management including benchmarking and standard treatment(OPTIMIsE)study in ***:"Benchmarking"is the process of receiving feedback comparing one’s performance with that of *** OPTIMIsE(NCT00681850)study is a multinational,multicenter study assessing,at a primary care level,whether using"benchmarking"can help to improve the quality of patient care,compared with a set of guideline-based reference values("non-benchmarking").In the Greek region,797 outpatients(457men,mean age 63.8 years)with type 2 diabetes were enrolled by 84 office-based *** characteristics of this population are ***:Hypertension was the most prevalent concomitant disorder(77.3%)and coronary heart disease was the most frequent macrovascular complication of diabetes(23.8%).Most patients were overweight or obese(body mass index 29.6±5 kg/m2),exhibiting mostly abdominal obesity(waist circumference102.6±13.6 cm).Biguanides were the most prevalent prescribed drugs for the management of diabetes(70.1%of all prescriptions),whereas statins(93.5%of all prescriptions)and angiotensin receptor blockers(55.8%of all prescriptions)were the most prevalent prescribed drugs for hyperlipidemia and hypertension,*** 37.4%of patients were on *** treatment,pre-defined targets for fasting plasma glucose(systolic blood pressure(s with proteinuria)and low density lipoprotein cholesterol levels(s with coronary heart disease)were reached in a relatively small proportion of patients(29%,53%,27%and 31%,respectively).In a Greek population with type 2 diabetes,the control of glycemia or concomitant disorders which increase cardiovascular risk remains ***:Despite relevant treatment,there is a poor control of diabetes,hypertension and hyperlipidemia in Greek outpatients with type 2 diabetes

关键词： Diabetes Benchmarking Treatment tar-get Glycemic control Dyslipidemia Blood pressure

Combination drug treatment in patients with non-alcoholic fatty liver disease

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World Journal of Hepatology 2010年第4期2卷 139-142页

作者： Theodosios D Filippatos moses s elisaf Department of Internal Medicine University of Ioannina Ioannina 45110 Greece

Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis, a benign condition, and non-alcoholic steatohepatitis, a condition that beyond TG accumulation also includes necroinflammation and fibrosis. An association between NAFLD and cardiovascular disease (CVD) has been recently suggested. NAFLD patients usually have an increased CVD risk profile. NAFLD is also associated with metabolic syndrome (Mets) and is considered as the hepatic component of Mets by some authors. Currently, the only established treatment of NAFLD is gradual weight loss. However, multifactorial treatment of NAFLD risk factors may be needed to reduce the increased CVD risk of NALFD patients. Drug combinations that include antiobesity drugs (such as orlistat and sibutramine) and target CVD risk factors may be a good approach to NAFLD patients. Our group has investigated the orlistat-fenofibrate combination treatment in obese patients with Mets and the orlistatezetimibe and sibutramine-antihypertensive combination treatment in obese patients with hyperlipidaemia with promising results in CVD risk factor reduction and improvement of liver function tests. small studies give promising results but double-blind, randomized trials examining the effects of such multifactorial treatment in hard CVD endpoints in NAFLD patients are missing.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Treatment Orlistat sibutramine Fenofibrate Ezetimibe Weight loss

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

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World Journal of Hepatology 2013年第9期5卷 470-478页

作者： Michael s Kostapanos Anastazia Kei moses s elisaf Department of Internal Medicine School of MedicineUniversity of Ioannina45110 IoanninaGreece

Non-alcoholic fatty liver disease(NAFLD) is a common health problem with a high mortality burden due to its liver- and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus(T2DM) and metabolic syndrome(Mets).Impaired hepatic fatty acid(FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors(PPARs)are involved in lipid and glucose metabolic *** novel concept is that the activation of the PPARαsubunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and Mets. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis *** include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet,T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were *** this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

关键词： Fenofibrate Non-alcoholic fatty liver disease steatohepatitis Peroxisome proliferator-activated receptors