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Thiazide-associated hyponatremia in the elderly： what the clinician needs to know

Journal of Geriatric Cardiology 2016年第2期13卷 175-182页

作者： George Liamis Theodosios D Filippatos moses s elisaf Department of Internal Medicine School of Medicine University of loannina Ioannina Greece

Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antide- pressants. sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clini- cians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inap- propriate antidiuretic hormone secretion （sIADH）. The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides （extracellular volume depletion-related or sIADH-like）. Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.

关键词： Antidiuretic hormone Diuretics Hyponatremia Potassium sodium Thiazides

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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

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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

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Nicotinic acid: Do we know how it works after 55 years of clinical experience?

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World Journal of Pharmacology 2012年第3期1卷 50-54页

作者： Anastazia Kei moses s elisaf Department of Internal Medicine School of Medicine University of Ioannina 45110 Ioannina Greece

Nicotinic acid （NA） comprises the oldest hypolipidemic drug, in use since 1955. Despite its established broad spectrum effect on lipid profle and the associated re-duction in cardiovascular morbidity and mortality, the mechanisms by which NA achieves its benefcial effects remain elusive. Regarding the NA-associated reduction in triglyceride and low density lipoprotein cholesterol levels, data are controversial. The prevailing view which suggested that NA inhibits lipolysis and decreases free fatty acid （FFA） release both via activation of adipose tissue G-protein receptor-109A （GPR109A） and via inhibition of hepatic triglyceride synthesis is currently debated by the observation that the initially decreased FFA levels rebound during long-term NA treatment even though the benefcial NA effects on lipid metabo-lism are preserved, while other mechanisms involving modulation of transcription and translation pathways are emerging. In addition, NA has been demonstrated to affect high density lipoprotein （HDL） particles remod-eling in a number of ways, including reducing choles-terol ester transfer protein levels and activity, increas-ing apolipoprotein A-I levels, eliminating HDL hepatic uptake, increasing cholesterol efflux via ATP-binding cassette A1, inhibiting hepatic lipase, thereby overall in-creasing the plasma residence time of HDL and apoA-I with retention of cholesterol esters in HDL. Focus of this article is to present the mechanisms by which NA exerts its broad spectrum hypolipidemic actions.

关键词： Dyslipidemia Nicotinic acid Niacin Mechanisms GPR109A Free fatty acids

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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

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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

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Proton pump inhibitor-induced hypomagnesemia: A new challenge

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World Journal of Nephrology 2012年第6期1卷 151-154页

作者： Matilda Florentin moses s elisaf Department of Internal Medicine Medical School University of Ioannina Ioannina 45110 Greece

Proton pump inhibitors （PPIs） are commonly used in clinical practice for the prevention and treatment of peptic ulcer, gastritis, esophagitis and gastroesophageal refux. Hypomagnesemia has recently been recognized as a side effect of PPIs. Low magnesium levels may cause symptoms from several systems, some of which being potentially serious, such as tetany, seizures and arrhythmias. It seems that PPIs affect the gastrointesti-nal absorption of magnesium. Clinicians should be vigi-lant in order to timely consider and prevent or reverse hypomagnesemia in patients who take PPIs, especially if they are prone to this electrolyte disorder.

关键词： Hypocalcemia Hypokalemia Hypomag-nesemia Proton pump inhibitors Transient receptor potential melastatin

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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

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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： Hyperkalemia Blood transfusions Packed red blood cells Renal function Gastrointestinal bleeding

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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

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