- Email: [email protected]
The effect of insulin analog initiation therapy on plasma polyunsaturated fatty acids during early phase
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Abstracts / Atherosclerosis 235 (2014) e84–e191
1. Uda et al., Tumour Biol. (2012) 2. Uda et al., J Lipid Res. (2013) 3. Luker et al., J Biol Chem. (1999) 36 - Cellular lipid metabolism EAS-1072. A SALMON PROTEIN HYDROLYSATE EXCERTS LIPID-INDEPENDENT ANTI-ATHEROSCLEROTIC ACTIVITY IN APOE-DEFICIENT MICE R. Vika, C. Parolinab, B. Bjørndala, A. Busnellib, S. Holmc, T. Brattelidd, S. Manzinib, G.S. Ganzettib, B. Halvorsenc, P. Aukrustc, C.R. Sirtorib, J.E. Nordrehauga, J. Skorvea, R. Bergea, G. Chiesab a Department of Clinical Science, University of Bergen, Bergen, Norway; b Dept of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; c Research Institute of Internal Medicine, Rikshospitalet University Hospital, Oslo, Norway; d NIFES, National Institute of Nutrition and Seafood Research, Bergen, Norway
Objectives: Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD) risk perhaps through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have antiatherosclerotic and anti-inflammatory properties. Methods: Twenty-four apolipoprotein (apo) E-/- mice were fed a high-fat diet with or without 5% SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. Results: A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in apolipoprotein apoE-/- mice fed 5% SPH for 12 weeks compared to a casein control diet. This was accompanied by reduced mRNA levels of Vcam1, Icam1 and Mcp1 in the aortic arch. The plasma content of arachidonic acid (C20:4n-6) and oleic acid (C18:1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1b, IL-6, TNF-a, GM-CSF and G-CSF, whereas the plasma content of cholesterol and triacylglycerols (TAGs) were unchanged. Liver TAGs were decreased in the SPH-fed group, accompanied by indication of decreased lipogenesis. Conclusion: These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE-/- mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids. 36 - Cellular lipid metabolism EAS-0909. THE POLYPHENOL CURCUMIN PROMOTES EXOSOMES SECRETION WHICH ATTENUATES LYSOSOMAL CHOLESTEROL TRAFFIC IMPAIRMENT A. Canfrán-Duquea, M. Lermaa, M.E. Casadoa, O. Pastorb, G. de la Peñaa, A. Martín-Hidalgoa, M.A. Lasuncióna, R. Bustoa a Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal IRYCIS and CIBERobn, Madrid, Spain; b Servicio de Bioquímica-Clínica, Hospital Universitario Ramón y Cajal IRYCIS, Madrid, Spain
Objectives: Exosomes are originated from multivascular bodies which allow the secretion of endolysosome components out of the cell. In the present work we investigated the effects of curcumin, the main active polyphenol extracted from the rhizome of Curcuma longa, on exosomes secretion in different cells lines, using U18666A as a model of intracellular cholesterol trafficking impairment. Methods: The HepG2 hepatocarcinoma cells and THP-1 differentiated macrophages were used in this studied. The methods utilized were inmunocytochemistry, DiI-LDL uptake by flow cytometry, cholesterol efflux assays, analysis of sterols by gas chromatography mass spectrometry; and exosomes were isolated and then analyzed by western-blot, electron microscopy and bead fluorescence-activated cell sorting.
Results: In both cells line, the treatment with curcumin affected the size and the localization of endosome/lysosomes accumulated by U18666A, and reduced the cholesterol cell content. To ascertain the mechanism, we analyzed the incubation medium. Curcumin stimulated the release of cholesterol and the lysosomal b-hexosaminidase enzyme, as well as the exosome markers, flotillin-2 and CD63. Electron microscopy studies demonstrated the presence of small vesicles similar to exosomes in the secretion fluid. These vesicles harbored CD63 on their surface, indicative of their endolysosomal origin. These effects of curcumin were particularly intense in cells treated with U18666A. Conclusion: These findings indicate that curcumin ameliorates the U18666A-induced endolysosomal cholesterol accumulation by shuttling cholesterol and presumably other lipids out of the cell via exosomes secretion. This action may contribute to the potential of curcumin in the treatment of lysosomal storage diseases. 36 - Cellular lipid metabolism EAS-0539. RESTORING CD36 TRAFFICKING: DIABETIC CARDIOMYOPATHY
NOVEL
ROADS
FOR
TREATING
J.J.F.P. Luiken, J.F.C. Glatz Molecular Genetics, Maastricht University, Maastricht, Netherlands Background: Western lifestyle, especially lipid overconsumption, causes myocellular lipid accumulation, lipid-induced insulin resistance, and finally impaired cardiac function (diabetic cardiomyopathy). Previously, we identified CD36 as the major cardiac fatty acid transporter and disclosed its major role in the etiology of high fat diet-induced cardiac contractile dysfunction. Specifically, a permanent relocation of this transporter from intracellular compartments (endosomes) to the sarcolemma fuels a vicious cycle of increased CD36-mediated LCFAuptake, subsequent accumulation of toxic lipid metabolites (lipotoxicity), lipid-induced insulin resistance, and finally cardiac dysfunction. In cardiomyocytes cultured under lipid-overload conditions, immunochemical CD36 inhibition prevented lipid accumulation and preserved contractile function, thereby providing proof-of-principle for the use of CD36 as an antidiabetic target (Angin, Biochem-J 448:43-53; 2012). We hypothesize that manipulation of subcellular trafficking processes aimed at internalizing CD36 away from the sarcolemma back to the endosomes also would represent a useful antidiabetic strategy. The CD36-dedicated trafficking machinery is poorly characterized, but likely encompasses isoforms of protein families with known functions in vesicular trafficking, i.e., SNARE proteins, rabs, coat proteins, etc. Methods: Isoforms of trafficking protein families specifically occurring in the heart were selected for genetic/pharmacological manipulation in cardiomyocytes cultured under basal or diabetogenic conditions. Thereafter, CD36 trafficking, insulin signaling, and toxic lipid metabolites were measured and contractile function evaluated. Results: We identified specific trafficking proteins to be involved in CD36 trafficking (VAMP3 and 4, rab11 and adaptor proteins, b-COP, vesiculartype ATPase), and excluded others (VAMP5 and 7, F-actin, tubulin). Overexpression of VAMP3 and overactivation of v-ATPase in cardiac myocytes each were found to prevent excess CD36 presence on the sarcolemma and protect against lipid-induced insulin resistance and contractile dysfunction of these myocytes. Conclusion: The CD36-dedicated trafficking machinery provides a set of novel protein targets to combat lipid-induced diabetic cardiomyopathy. 37 - Diabetes, insulin sensitivity and resistance EAS-0010. THE EFFECT OF INSULIN ANALOG INITIATION THERAPY ON PLASMA POLYUNSATURATED FATTY ACIDS DURING EARLY PHASE I. Aslan MD a, M. Aslan MD b
Abstracts / Atherosclerosis 235 (2014) e84–e191 a Endocrinology and Metabolism, Antalya Training and Research Hospital, Antalya, Turkey; b Department of Medical Biochemistry, Akdeniz University Medical School, Antalya, Turkey
Objectives: This study was designed to evaluate the effect of insulin analog initiation therapy on n6 and n3 PUFAs in type 2 diabetic patients during early phase. Methods: Sixteen type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of arachidonic acid (AA, C20:4n6), dihomo-gammalinolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fastliquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Results: All measured PUFAs were significantly increased after treatment with insulin analogs plus metformin compared to before treatment levels. The mean AA/EPA ratio was significantly lower after treatment with insulin analogs plus metformin. Conclusion: The significant decrease in AA/EPA ratio indicates that insulin analog initiation therapy has anti-inflammatory properties by favoring the increase of n-3 fatty acid EPA. 37 - Diabetes, insulin sensitivity and resistance EAS-0503. EFFECT OF MAGNESIUM SUPPLEMENTATION ON METABOLIC CONTROL AND INSULIN SENSITIVITY IN TYPE 2 DIABETIC PATIENTS J.L. Ble-Castilloa, A. Navarrete-Cortesb, F. Guerrero-Romeroc, R. Cordova-Uscangab, I.E. Juarez-Rojopa, H. Aguilar-Mariscala, C.A. Tovilla-Zarated, M.R. López-Guevarab, J.C. Diaz-Zagoyaa a
Division Academica de Ciencias de la Salud, Universidad Juarez Autonoma de Tabasco, Villahermosa, Mexico; b Hospital General de Zona 46, Instituto Mexicano del Seguro Social, Villahermosa, Mexico; c Unidad de Investigación Médica en Epidemiología Clínica, Instituto Mexicano del Seguro Social, Durango, Mexico; d División Académica Multidisciplinaria de Comalcalco, Universidad Juarez Autonoma de Tabasco, Villahermosa, Mexico Objectives: Diabetes is a major risk factor for cardiovascular disease. The goal for reducing complications is to maintain a good metabolic control. There are limited and conflicting data from trials concerning the beneficial effects of magnesium supplementation. The aim of the present study was to examine the effects of oral magnesium supplementation on the metabolic control and insulin sensitivity in type 2 diabetic patients. Methods: We undertook this randomized, crossover, double blind placebo controlled trial in 98 type 2 diabetic subjects who were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for 3 months with a 3 months of washout period. Fasting blood and 24 h urine specimen were collected at the beginning and end of each treatment period. Sixty-five subjects finished the study Results: Serum magnesium in diabetics was significantly lower than in the healthy population, however, no hypomagnesemia was observed. A significant inverse relation between the serum magnesium and fast glycemia was observed in diabetics. Urinary magnesium excretion was increased after magnesium supplementation compared with the placebo. Conclusion: Magnesium supplementation did not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia
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37 - Diabetes, insulin sensitivity and resistance EAS-0069. EFFECTS OF HYPOLIPIDEMIC DRUGS (ATORVASTATIN, FENOFIBRATE AND COMBINED TREATMENT) ON INSULIN RESISTANCE INDEX, ADIPOKINES AND INFLAMMATORY MARKERS IN DYSLIPIDEMIC SUBJECTS L. Buldak MD a, B. Okopien MD a, R. Krysiak MD a, K. Labuzek MD a, A. Dulawa-Buldak MD b a Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia in Katowice, Katowice, Poland; b Department of Anaestesiology and Intensive Care, Medical University of Silesia in Katowice, Katowice, Poland
Objectives: Concerns regarding worsening of insulin sensitivity during statin therapy were recently suggested. Therefore we aimed to evaluate the influence of hypolipidemic treatment with atorvastatin, fenofibrate and combined treatment on insulin resistance index (HOMA-IR), adipokines and proinflammatory cytokines level. Methods: 53 obese or overweight subjects with mixed dyslipidemia and impaired glucose tolerance underwent randomization into the treatment consisting of 10mg atorvastatin (A) or 267mg fenofibrate (F) or combined therapy (C) with 10mg atorvastatin and 267mg fenofibrate. The study lasted for 90 days. Fasting glucose and fasting insulin levels were used to calculate HOMA-IR. Adipokines and proinflammatory cytokines were assayed using commercially available kits. Results: At the beginning of the study demographic variables, HOMA-IR, proinflammatory cytokines and adipokines levels were similar in all groups. After 90 days of treatment a significant improvement in insulin resistance (HOMA-IR) was observed in patients treated with (F) and (C) vs. baseline values (3.82.4vs.5.11.8; p Conclusion: Fenofibrate-based therapy most potently reduced HOMA-IR and increased adiponectin level therefore it seems to posses beneficial effects on carbohydrate metabolism. We did not observe detoriation in glucose tolerance after the therapy with atorvastatin. Both therapies reduced inflammatory cytokines concentration but combined treatment resulted in even more profound reduction in IL-6 level. 37 - Diabetes, insulin sensitivity and resistance EAS-0118. IMPACT OF DIFFERENT CRITERIA ON TYPE 2 DIABETES REMISSION RATE AFTER BARIATRIC SURGERY M. Antonioa, P. Juana, B. Davida, F. Juanaa, R. Jose Manuelb, C. Juan Joséa, P. Alejandraa, V. Montserrata, P.E.R.A. Manuelb, G. Alberta Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain; b Surgery, Hospital del Mar, Barcelona, Spain
a
Objectives: Laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) achieve similar type 2 diabetes mellitus (T2DM) remission rates. Since a great variability exits in defining T2DM remission, an expert panel proposed partial and complete remission criteria that include the maintenance of fasting plasma glucose (FPG) and A1c objectives for at least one year. The 2-year T2DM remission rate and time needed to reach it after LSG or LRYGB were compared using different remission criteria. Methods: Prospective cohort study of 55 T2DM subjects operated on with LSG (n¼21) or LRYGB (n¼34). Four models for defining remission were used: Classical criteria (FPG <100 mg/dl or A1c <6%); ADA complete (FPG <100 mg/dl plus A1c <6% maintained for at least one year); ADA partial (FPG <125 mg/dl with A1c< 6.5% maintained for at least one year); and ADA complete without time requirement. Results: All 55 diabetic patients were Caucasian, with a mean age of 49.0 4.9 years and a baseline BMI of 45.4 4.9 Kg/m2; 80% were women.
Abstracts / Atherosclerosis 235 (2014) e84–e191
1. Uda et al., Tumour Biol. (2012) 2. Uda et al., J Lipid Res. (2013) 3. Luker et al., J Biol Chem. (1999) 36 - Cellular lipid metabolism EAS-1072. A SALMON PROTEIN HYDROLYSATE EXCERTS LIPID-INDEPENDENT ANTI-ATHEROSCLEROTIC ACTIVITY IN APOE-DEFICIENT MICE R. Vika, C. Parolinab, B. Bjørndala, A. Busnellib, S. Holmc, T. Brattelidd, S. Manzinib, G.S. Ganzettib, B. Halvorsenc, P. Aukrustc, C.R. Sirtorib, J.E. Nordrehauga, J. Skorvea, R. Bergea, G. Chiesab a Department of Clinical Science, University of Bergen, Bergen, Norway; b Dept of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; c Research Institute of Internal Medicine, Rikshospitalet University Hospital, Oslo, Norway; d NIFES, National Institute of Nutrition and Seafood Research, Bergen, Norway
Objectives: Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD) risk perhaps through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have antiatherosclerotic and anti-inflammatory properties. Methods: Twenty-four apolipoprotein (apo) E-/- mice were fed a high-fat diet with or without 5% SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. Results: A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in apolipoprotein apoE-/- mice fed 5% SPH for 12 weeks compared to a casein control diet. This was accompanied by reduced mRNA levels of Vcam1, Icam1 and Mcp1 in the aortic arch. The plasma content of arachidonic acid (C20:4n-6) and oleic acid (C18:1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1b, IL-6, TNF-a, GM-CSF and G-CSF, whereas the plasma content of cholesterol and triacylglycerols (TAGs) were unchanged. Liver TAGs were decreased in the SPH-fed group, accompanied by indication of decreased lipogenesis. Conclusion: These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE-/- mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids. 36 - Cellular lipid metabolism EAS-0909. THE POLYPHENOL CURCUMIN PROMOTES EXOSOMES SECRETION WHICH ATTENUATES LYSOSOMAL CHOLESTEROL TRAFFIC IMPAIRMENT A. Canfrán-Duquea, M. Lermaa, M.E. Casadoa, O. Pastorb, G. de la Peñaa, A. Martín-Hidalgoa, M.A. Lasuncióna, R. Bustoa a Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal IRYCIS and CIBERobn, Madrid, Spain; b Servicio de Bioquímica-Clínica, Hospital Universitario Ramón y Cajal IRYCIS, Madrid, Spain
Objectives: Exosomes are originated from multivascular bodies which allow the secretion of endolysosome components out of the cell. In the present work we investigated the effects of curcumin, the main active polyphenol extracted from the rhizome of Curcuma longa, on exosomes secretion in different cells lines, using U18666A as a model of intracellular cholesterol trafficking impairment. Methods: The HepG2 hepatocarcinoma cells and THP-1 differentiated macrophages were used in this studied. The methods utilized were inmunocytochemistry, DiI-LDL uptake by flow cytometry, cholesterol efflux assays, analysis of sterols by gas chromatography mass spectrometry; and exosomes were isolated and then analyzed by western-blot, electron microscopy and bead fluorescence-activated cell sorting.
Results: In both cells line, the treatment with curcumin affected the size and the localization of endosome/lysosomes accumulated by U18666A, and reduced the cholesterol cell content. To ascertain the mechanism, we analyzed the incubation medium. Curcumin stimulated the release of cholesterol and the lysosomal b-hexosaminidase enzyme, as well as the exosome markers, flotillin-2 and CD63. Electron microscopy studies demonstrated the presence of small vesicles similar to exosomes in the secretion fluid. These vesicles harbored CD63 on their surface, indicative of their endolysosomal origin. These effects of curcumin were particularly intense in cells treated with U18666A. Conclusion: These findings indicate that curcumin ameliorates the U18666A-induced endolysosomal cholesterol accumulation by shuttling cholesterol and presumably other lipids out of the cell via exosomes secretion. This action may contribute to the potential of curcumin in the treatment of lysosomal storage diseases. 36 - Cellular lipid metabolism EAS-0539. RESTORING CD36 TRAFFICKING: DIABETIC CARDIOMYOPATHY
NOVEL
ROADS
FOR
TREATING
J.J.F.P. Luiken, J.F.C. Glatz Molecular Genetics, Maastricht University, Maastricht, Netherlands Background: Western lifestyle, especially lipid overconsumption, causes myocellular lipid accumulation, lipid-induced insulin resistance, and finally impaired cardiac function (diabetic cardiomyopathy). Previously, we identified CD36 as the major cardiac fatty acid transporter and disclosed its major role in the etiology of high fat diet-induced cardiac contractile dysfunction. Specifically, a permanent relocation of this transporter from intracellular compartments (endosomes) to the sarcolemma fuels a vicious cycle of increased CD36-mediated LCFAuptake, subsequent accumulation of toxic lipid metabolites (lipotoxicity), lipid-induced insulin resistance, and finally cardiac dysfunction. In cardiomyocytes cultured under lipid-overload conditions, immunochemical CD36 inhibition prevented lipid accumulation and preserved contractile function, thereby providing proof-of-principle for the use of CD36 as an antidiabetic target (Angin, Biochem-J 448:43-53; 2012). We hypothesize that manipulation of subcellular trafficking processes aimed at internalizing CD36 away from the sarcolemma back to the endosomes also would represent a useful antidiabetic strategy. The CD36-dedicated trafficking machinery is poorly characterized, but likely encompasses isoforms of protein families with known functions in vesicular trafficking, i.e., SNARE proteins, rabs, coat proteins, etc. Methods: Isoforms of trafficking protein families specifically occurring in the heart were selected for genetic/pharmacological manipulation in cardiomyocytes cultured under basal or diabetogenic conditions. Thereafter, CD36 trafficking, insulin signaling, and toxic lipid metabolites were measured and contractile function evaluated. Results: We identified specific trafficking proteins to be involved in CD36 trafficking (VAMP3 and 4, rab11 and adaptor proteins, b-COP, vesiculartype ATPase), and excluded others (VAMP5 and 7, F-actin, tubulin). Overexpression of VAMP3 and overactivation of v-ATPase in cardiac myocytes each were found to prevent excess CD36 presence on the sarcolemma and protect against lipid-induced insulin resistance and contractile dysfunction of these myocytes. Conclusion: The CD36-dedicated trafficking machinery provides a set of novel protein targets to combat lipid-induced diabetic cardiomyopathy. 37 - Diabetes, insulin sensitivity and resistance EAS-0010. THE EFFECT OF INSULIN ANALOG INITIATION THERAPY ON PLASMA POLYUNSATURATED FATTY ACIDS DURING EARLY PHASE I. Aslan MD a, M. Aslan MD b
Abstracts / Atherosclerosis 235 (2014) e84–e191 a Endocrinology and Metabolism, Antalya Training and Research Hospital, Antalya, Turkey; b Department of Medical Biochemistry, Akdeniz University Medical School, Antalya, Turkey
Objectives: This study was designed to evaluate the effect of insulin analog initiation therapy on n6 and n3 PUFAs in type 2 diabetic patients during early phase. Methods: Sixteen type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of arachidonic acid (AA, C20:4n6), dihomo-gammalinolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fastliquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Results: All measured PUFAs were significantly increased after treatment with insulin analogs plus metformin compared to before treatment levels. The mean AA/EPA ratio was significantly lower after treatment with insulin analogs plus metformin. Conclusion: The significant decrease in AA/EPA ratio indicates that insulin analog initiation therapy has anti-inflammatory properties by favoring the increase of n-3 fatty acid EPA. 37 - Diabetes, insulin sensitivity and resistance EAS-0503. EFFECT OF MAGNESIUM SUPPLEMENTATION ON METABOLIC CONTROL AND INSULIN SENSITIVITY IN TYPE 2 DIABETIC PATIENTS J.L. Ble-Castilloa, A. Navarrete-Cortesb, F. Guerrero-Romeroc, R. Cordova-Uscangab, I.E. Juarez-Rojopa, H. Aguilar-Mariscala, C.A. Tovilla-Zarated, M.R. López-Guevarab, J.C. Diaz-Zagoyaa a
Division Academica de Ciencias de la Salud, Universidad Juarez Autonoma de Tabasco, Villahermosa, Mexico; b Hospital General de Zona 46, Instituto Mexicano del Seguro Social, Villahermosa, Mexico; c Unidad de Investigación Médica en Epidemiología Clínica, Instituto Mexicano del Seguro Social, Durango, Mexico; d División Académica Multidisciplinaria de Comalcalco, Universidad Juarez Autonoma de Tabasco, Villahermosa, Mexico Objectives: Diabetes is a major risk factor for cardiovascular disease. The goal for reducing complications is to maintain a good metabolic control. There are limited and conflicting data from trials concerning the beneficial effects of magnesium supplementation. The aim of the present study was to examine the effects of oral magnesium supplementation on the metabolic control and insulin sensitivity in type 2 diabetic patients. Methods: We undertook this randomized, crossover, double blind placebo controlled trial in 98 type 2 diabetic subjects who were randomly assigned to receive magnesium lactate (360 mg elemental magnesium) or placebo for 3 months with a 3 months of washout period. Fasting blood and 24 h urine specimen were collected at the beginning and end of each treatment period. Sixty-five subjects finished the study Results: Serum magnesium in diabetics was significantly lower than in the healthy population, however, no hypomagnesemia was observed. A significant inverse relation between the serum magnesium and fast glycemia was observed in diabetics. Urinary magnesium excretion was increased after magnesium supplementation compared with the placebo. Conclusion: Magnesium supplementation did not improve metabolic control or insulin sensitivity in diabetic subjects with normomagnesemia
e189
37 - Diabetes, insulin sensitivity and resistance EAS-0069. EFFECTS OF HYPOLIPIDEMIC DRUGS (ATORVASTATIN, FENOFIBRATE AND COMBINED TREATMENT) ON INSULIN RESISTANCE INDEX, ADIPOKINES AND INFLAMMATORY MARKERS IN DYSLIPIDEMIC SUBJECTS L. Buldak MD a, B. Okopien MD a, R. Krysiak MD a, K. Labuzek MD a, A. Dulawa-Buldak MD b a Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia in Katowice, Katowice, Poland; b Department of Anaestesiology and Intensive Care, Medical University of Silesia in Katowice, Katowice, Poland
Objectives: Concerns regarding worsening of insulin sensitivity during statin therapy were recently suggested. Therefore we aimed to evaluate the influence of hypolipidemic treatment with atorvastatin, fenofibrate and combined treatment on insulin resistance index (HOMA-IR), adipokines and proinflammatory cytokines level. Methods: 53 obese or overweight subjects with mixed dyslipidemia and impaired glucose tolerance underwent randomization into the treatment consisting of 10mg atorvastatin (A) or 267mg fenofibrate (F) or combined therapy (C) with 10mg atorvastatin and 267mg fenofibrate. The study lasted for 90 days. Fasting glucose and fasting insulin levels were used to calculate HOMA-IR. Adipokines and proinflammatory cytokines were assayed using commercially available kits. Results: At the beginning of the study demographic variables, HOMA-IR, proinflammatory cytokines and adipokines levels were similar in all groups. After 90 days of treatment a significant improvement in insulin resistance (HOMA-IR) was observed in patients treated with (F) and (C) vs. baseline values (3.82.4vs.5.11.8; p Conclusion: Fenofibrate-based therapy most potently reduced HOMA-IR and increased adiponectin level therefore it seems to posses beneficial effects on carbohydrate metabolism. We did not observe detoriation in glucose tolerance after the therapy with atorvastatin. Both therapies reduced inflammatory cytokines concentration but combined treatment resulted in even more profound reduction in IL-6 level. 37 - Diabetes, insulin sensitivity and resistance EAS-0118. IMPACT OF DIFFERENT CRITERIA ON TYPE 2 DIABETES REMISSION RATE AFTER BARIATRIC SURGERY M. Antonioa, P. Juana, B. Davida, F. Juanaa, R. Jose Manuelb, C. Juan Joséa, P. Alejandraa, V. Montserrata, P.E.R.A. Manuelb, G. Alberta Endocrinology and Nutrition, Hospital del Mar, Barcelona, Spain; b Surgery, Hospital del Mar, Barcelona, Spain
a
Objectives: Laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) achieve similar type 2 diabetes mellitus (T2DM) remission rates. Since a great variability exits in defining T2DM remission, an expert panel proposed partial and complete remission criteria that include the maintenance of fasting plasma glucose (FPG) and A1c objectives for at least one year. The 2-year T2DM remission rate and time needed to reach it after LSG or LRYGB were compared using different remission criteria. Methods: Prospective cohort study of 55 T2DM subjects operated on with LSG (n¼21) or LRYGB (n¼34). Four models for defining remission were used: Classical criteria (FPG <100 mg/dl or A1c <6%); ADA complete (FPG <100 mg/dl plus A1c <6% maintained for at least one year); ADA partial (FPG <125 mg/dl with A1c< 6.5% maintained for at least one year); and ADA complete without time requirement. Results: All 55 diabetic patients were Caucasian, with a mean age of 49.0 4.9 years and a baseline BMI of 45.4 4.9 Kg/m2; 80% were women.