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Target attainment of multifactorial treatment in diabetic patients in a specialized clinic
Abstracts / Atherosclerosis 241 (2015) e149ee229
smokers, had impaired lipid metabolism, high blood pressure, severe coronary artery lesions EAS-0374. CYCLIC ANTITHROMBOTIC AGENTS WITH NON-RGD LIKE ACTIVITY P. Trypou*, V. Moussis, E. Malissiova, V.G. Chantzichristos, A.D. Tselepis, V. Tsikaris. Section of Organic Chemistry & Biochemistry, University of Ioannina, Ioannina, Greece
* Corresponding author. The platelet fibrinogen receptor, integrin aIIbb3, plays a key role in hemostasis and thrombosis. During platelet activation, conformational changes of the receptor convert aIIbb3 from a low- to a high affinity state (able to bind ligands through the Arg-Gly-Asp sequence), resulting in platelet aggregation. Inhibition of this process can be achieved by RGD peptide analogues that bind to aIIbb3 receptor. In current antiplatelet therapy there are available two RGD based drugs. However, this class of inhibitors upon binding to receptor cause an outside-in signaling which induces a further activation of the platelet. In previous studies we presented cyclic (S,S)eCDCe containing compounds and aIIb derived sequences that exhibit a non-RGD-like inhibitory activity. The aim of this study was to design, synthesize and test for their inhibitory activity new cyclic compounds. Peptides were synthesized using the standard Fmoc methodology. The formation of the disulfide bond was performed using Tl(tfa)3 or NCS. Platelet aggregation to ADP(10mM) in platelet rich plasma was determined using light transmission aggregometry and the % inhibition of platelet aggregation (IPA) values versus baseline were estimated.
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was significantly decreased in this group. All diabetic groups revealed decreased relative n-3 PUFA amount (3,35 D t.1 vs 3,40 D t.2 vs 4,68 control, p<0,001) related to decreased DHA, not EPA. GIP level positively correlated with (C<20) SFA and MUFA and negatively with (C20) FA and PUFA. Conclusions: The detailed plasma lipids study revealed the associations of GIP blood concentration with fatty acids profile and suggest, that this gut hormone level may reflect disturbed FA metabolism (ineffective desaturase and elongase action). Thus, GIP plasma level may also indicate subjects who would potentially benefit from n-3 PUFA supplementation. Supported by NCN grant no. K/PBN/000001; EU FP7 BIOCLAMS, Grant no. 244995, grants K/ZDS/002442 and K/ZDS/004501.
EAS-0437. TARGET ATTAINMENT OF MULTIFACTORIAL TREATMENT IN DIABETIC PATIENTS IN A SPECIALIZED CLINIC F. Barkas*, E. Liberopoulos, G. Liamis, A. Liontos, T. Panagiotopoulou, E. Moses. Internal Medicine, School of Medicine University of Ioannina, Ioannina, Greece
* Corresponding author. Aim: To assess goal achievement of lipid-lowering, antihypertensive and antidiabetic therapy in diabetic patients in a specialized clinic. Methods: This was a retrospective study including consecutive adults with a follow-up 3 years. Low-density lipoprotein cholesterol (LDL-C), blood pressure (BP) and glycated hemoglobin (HbA1c) goals achievement were
Peptide
IC50(mM)
Peptide
IC50(mM)
(S,S)DPro-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (S,S)His-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (S,S)His-Ser-Lys-Cys-Asp-Cys-Arg-NH2 (S,S)Tyr-Met-Glu-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (S,S)His-Ser-Orn-Cys-Asp-Cys-Arg-NH2
15 10 30 58 100
(S,S)Tyr-Met-Glu-Cys-Arg-Ala-Asp-Cys-Arg-NH2 (S,S)Tyr-Met(ox)-Glu-Cys-Arg-Ala-Asp-Cys-Arg-NH2 (S,S)Pro-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (Control) Tyr-Met-Glu-Ser-Arg-Ala-Asp-Arg-OH (Control)
166 193 2 250
In conclusion the biological assays revealed that the (S,S)-CDC- scaffold and also hybrid compounds (aIIb derived sequences incorporated with the -CDC- site) can be used for developing potent non-RGD-like antiplatelet agents. EAS-0411. RELATIONSHIPS OF GIP SECRETION WITH PLASMA FATTY ACIDS PROFILE IN DIABETIC PATIENTS ralska 1, *, B. Kiec-Wilk 2, M. Malczewska-Malec 1, U. Razny 1, P. J. Go Zabielski 3, A. Chabowski 3, A. Zdzienicka 1, B. Solnica 1, M. Malecki 2, A. Dembinska-Kiec 1. 1 Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland; 2 Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; 3 Department of Physiology, Medical University of Bialystok, Bialystok, Poland
* Corresponding author. Aim: Mechanism underlying associations of GIP with fat metabolism is not clear. The aim was to investigate plasma GIP level in relation to plasma concentration of 14 different fatty acids in diabetes type 1, diabetes type 2 and non-diabetic patients. Methods: A total of 93 subjects, included patients with diabetes type 1 (n¼13), diabetes type 2 (n¼33) and non-diabetic subjects (n¼45). Fasting plasma GIP and fatty acids profile were measured. Results: Fasting GIP plasma level was significantly increased in diabetes t.2 compared to diabetes type1 (44,45 vs 20,19pg/ml). The highest saturated to unsaturated (SFA/UFA) ratio was found in diabetes t.2 (0,52), and lowest in diabetes type 1 (0,45). Diabetes t.2 patients presented increased long chain (C<20) SFA, MUFA, and decreased PUFA. Although the highest amount of UFA was presented by diabetes t.1 patients, the n-3/n-6 ratio
recorded in those diagnosed with diabetes according to European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), European Society of Hypertension (ESH)/ESC and European Association for the Study of Diabetes (EASD) guidelines, respectively. Results: Of 1000 enrolled subjects, 211 were diagnosed with diabetes. Of those, 72% achieved the BP target (<140/85 mmHg). The rates of target attainment regarding low density lipoprotein cholesterol (LDL-C <70 mg/ dL) and non-high density lipoprotein cholesterol (non-HDL-C <100 mg/dL) were 35% kai 43%, respectively. Of the diabetic individuals, 72% had triglycerides levels <150 mg/dL. As far as glycemic target is concerned, 54.4% of the diabetics had HbA1c <7%, while only 26% achieved the more stringent HbA1c goal (<6.5%). Only 1 of 10 patients achieved all treatment targets simultaneously. Conclusion: Even in a setting of a specialized clinic, a high proportion of diabetic patients fails to achieve the targets of antihypertensive, lipid and glucose lowering treatment. EAS-0443. THE IMPACT OF SUPPORTED TELEMETRIC MONITORING IN PEOPLE WITH TYPE 2 DIABETES: THE TELESCOT RANDOMIZED CONTROLLED TRIAL S. Wild*. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom
* Corresponding author. Aim: Good control of glycaemia and blood pressure (BP) reduces complications in people with diabetes. The aim of this trial was to determine whether supported telemetric monitoring improves control of hyperglycaemia and BP in people with poorly controlled type 2 diabetes.
smokers, had impaired lipid metabolism, high blood pressure, severe coronary artery lesions EAS-0374. CYCLIC ANTITHROMBOTIC AGENTS WITH NON-RGD LIKE ACTIVITY P. Trypou*, V. Moussis, E. Malissiova, V.G. Chantzichristos, A.D. Tselepis, V. Tsikaris. Section of Organic Chemistry & Biochemistry, University of Ioannina, Ioannina, Greece
* Corresponding author. The platelet fibrinogen receptor, integrin aIIbb3, plays a key role in hemostasis and thrombosis. During platelet activation, conformational changes of the receptor convert aIIbb3 from a low- to a high affinity state (able to bind ligands through the Arg-Gly-Asp sequence), resulting in platelet aggregation. Inhibition of this process can be achieved by RGD peptide analogues that bind to aIIbb3 receptor. In current antiplatelet therapy there are available two RGD based drugs. However, this class of inhibitors upon binding to receptor cause an outside-in signaling which induces a further activation of the platelet. In previous studies we presented cyclic (S,S)eCDCe containing compounds and aIIb derived sequences that exhibit a non-RGD-like inhibitory activity. The aim of this study was to design, synthesize and test for their inhibitory activity new cyclic compounds. Peptides were synthesized using the standard Fmoc methodology. The formation of the disulfide bond was performed using Tl(tfa)3 or NCS. Platelet aggregation to ADP(10mM) in platelet rich plasma was determined using light transmission aggregometry and the % inhibition of platelet aggregation (IPA) values versus baseline were estimated.
e219
was significantly decreased in this group. All diabetic groups revealed decreased relative n-3 PUFA amount (3,35 D t.1 vs 3,40 D t.2 vs 4,68 control, p<0,001) related to decreased DHA, not EPA. GIP level positively correlated with (C<20) SFA and MUFA and negatively with (C20) FA and PUFA. Conclusions: The detailed plasma lipids study revealed the associations of GIP blood concentration with fatty acids profile and suggest, that this gut hormone level may reflect disturbed FA metabolism (ineffective desaturase and elongase action). Thus, GIP plasma level may also indicate subjects who would potentially benefit from n-3 PUFA supplementation. Supported by NCN grant no. K/PBN/000001; EU FP7 BIOCLAMS, Grant no. 244995, grants K/ZDS/002442 and K/ZDS/004501.
EAS-0437. TARGET ATTAINMENT OF MULTIFACTORIAL TREATMENT IN DIABETIC PATIENTS IN A SPECIALIZED CLINIC F. Barkas*, E. Liberopoulos, G. Liamis, A. Liontos, T. Panagiotopoulou, E. Moses. Internal Medicine, School of Medicine University of Ioannina, Ioannina, Greece
* Corresponding author. Aim: To assess goal achievement of lipid-lowering, antihypertensive and antidiabetic therapy in diabetic patients in a specialized clinic. Methods: This was a retrospective study including consecutive adults with a follow-up 3 years. Low-density lipoprotein cholesterol (LDL-C), blood pressure (BP) and glycated hemoglobin (HbA1c) goals achievement were
Peptide
IC50(mM)
Peptide
IC50(mM)
(S,S)DPro-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (S,S)His-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (S,S)His-Ser-Lys-Cys-Asp-Cys-Arg-NH2 (S,S)Tyr-Met-Glu-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (S,S)His-Ser-Orn-Cys-Asp-Cys-Arg-NH2
15 10 30 58 100
(S,S)Tyr-Met-Glu-Cys-Arg-Ala-Asp-Cys-Arg-NH2 (S,S)Tyr-Met(ox)-Glu-Cys-Arg-Ala-Asp-Cys-Arg-NH2 (S,S)Pro-Ser-Arg-Cys-Asp-Cys-Arg-NH2 (Control) Tyr-Met-Glu-Ser-Arg-Ala-Asp-Arg-OH (Control)
166 193 2 250
In conclusion the biological assays revealed that the (S,S)-CDC- scaffold and also hybrid compounds (aIIb derived sequences incorporated with the -CDC- site) can be used for developing potent non-RGD-like antiplatelet agents. EAS-0411. RELATIONSHIPS OF GIP SECRETION WITH PLASMA FATTY ACIDS PROFILE IN DIABETIC PATIENTS ralska 1, *, B. Kiec-Wilk 2, M. Malczewska-Malec 1, U. Razny 1, P. J. Go Zabielski 3, A. Chabowski 3, A. Zdzienicka 1, B. Solnica 1, M. Malecki 2, A. Dembinska-Kiec 1. 1 Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland; 2 Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; 3 Department of Physiology, Medical University of Bialystok, Bialystok, Poland
* Corresponding author. Aim: Mechanism underlying associations of GIP with fat metabolism is not clear. The aim was to investigate plasma GIP level in relation to plasma concentration of 14 different fatty acids in diabetes type 1, diabetes type 2 and non-diabetic patients. Methods: A total of 93 subjects, included patients with diabetes type 1 (n¼13), diabetes type 2 (n¼33) and non-diabetic subjects (n¼45). Fasting plasma GIP and fatty acids profile were measured. Results: Fasting GIP plasma level was significantly increased in diabetes t.2 compared to diabetes type1 (44,45 vs 20,19pg/ml). The highest saturated to unsaturated (SFA/UFA) ratio was found in diabetes t.2 (0,52), and lowest in diabetes type 1 (0,45). Diabetes t.2 patients presented increased long chain (C<20) SFA, MUFA, and decreased PUFA. Although the highest amount of UFA was presented by diabetes t.1 patients, the n-3/n-6 ratio
recorded in those diagnosed with diabetes according to European Society of Cardiology/European Atherosclerosis Society (ESC/EAS), European Society of Hypertension (ESH)/ESC and European Association for the Study of Diabetes (EASD) guidelines, respectively. Results: Of 1000 enrolled subjects, 211 were diagnosed with diabetes. Of those, 72% achieved the BP target (<140/85 mmHg). The rates of target attainment regarding low density lipoprotein cholesterol (LDL-C <70 mg/ dL) and non-high density lipoprotein cholesterol (non-HDL-C <100 mg/dL) were 35% kai 43%, respectively. Of the diabetic individuals, 72% had triglycerides levels <150 mg/dL. As far as glycemic target is concerned, 54.4% of the diabetics had HbA1c <7%, while only 26% achieved the more stringent HbA1c goal (<6.5%). Only 1 of 10 patients achieved all treatment targets simultaneously. Conclusion: Even in a setting of a specialized clinic, a high proportion of diabetic patients fails to achieve the targets of antihypertensive, lipid and glucose lowering treatment. EAS-0443. THE IMPACT OF SUPPORTED TELEMETRIC MONITORING IN PEOPLE WITH TYPE 2 DIABETES: THE TELESCOT RANDOMIZED CONTROLLED TRIAL S. Wild*. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom
* Corresponding author. Aim: Good control of glycaemia and blood pressure (BP) reduces complications in people with diabetes. The aim of this trial was to determine whether supported telemetric monitoring improves control of hyperglycaemia and BP in people with poorly controlled type 2 diabetes.