Abstract Schizophrenia is associated with a shortened life expectancy and increased somatic comorbidity with e.g. cardiovascular disorders. The purpose of this study was to evaluate hyperlipidemia and metabolic syndrome in schizophrenia and thus find specific risk factors for excess mortality and morbidity. The study population was a subsample of the Northern Finland 1966 Birth Cohort, a general population-based birth cohort. In 1997, 8,463 members of the cohort were invited to a clinical examination, where e.g. blood samples were taken after an overnight fast. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG) were determined. The following psychiatric diagnostic categories were used: 1) DSM-III-R schizophrenia (n = 31), 2) other psychoses (n = 21), 3) non-psychotic disorders (n = 104), 4) comparison group (n = 5,498), having no psychiatric hospital treatment. Mean TC (5.5 mmol/l) and TG (1.5 mmol/l) were significantly higher in the schizophrenia group than in the comparison group (5.1 mmol/l and 1.2 mmol/l, respectively). To evaluate serum lipid levels in subjects with and without antipsychotic medication the sample was analyzed according to used medication. The prevalence of hypercholesterolemia, high LDL cholesterol and hypertriglyceridemia was high in persons using antipsychotic medication (31%, 20% and 22%, respectively) compared to persons without such medication (12%, 10% and 7%, respectively). We found higher triglyceride levels in patients who were ≤ 20 years old at the onset of schizophrenia (mean 1.7 mmol/l; N = 17) as compared with patients with later onset (mean 1.4 mmol/l; N = 14) or non-hospitalized controls (mean 1.2 mmol/l; N = 5,453). The difference between the first and third group was significant (p < 0.01), and there was a negative correlation between the age at onset and the level of serum triglycerides (r = -0.35, p = 0.05). To evaluate the prevalence of metabolic syndrome, the subjects were assessed for the presence of metabolic syndrome according to the criteria of the National Cholesterol Education Program. The prevalence of metabolic syndrome was high in subjects with schizophrenia compared with the comparison group (19% vs. 6%, p = 0.010). The results indicate an elevated risk for hyperlipidemia and metabolic syndrome in persons with schizophrenia or on antipsychotic medication. Regular monitoring of weight, serum lipid and glucose levels and blood pressure is important. Comprehensive efforts directed at controlling weight and improving physical activity are needed.

Made available in DSpace on 2016-05-02T13:54:45Z (GMT). No. of bitstreams: 1 LuisaBarbosaMessora-dissertacao-completa.pdf: 574964 bytes, checksum: f3b5918f00bf09a802e755b11db471d0 (MD5) Previous issue date: 2010-11-21 / LDLr-/ - mice are spontaneously hyperlipidemic and resistant to the development of neointimal lesions. This study determined the influence of plasma levels of high density lipoprotein on cardiovascular inflammation, insulin resistance, and blood cell count in LDL (LDLr-/ -) receptor gene knockout mice. Three groups of 3-month-old male mice were used: Group WT, wild-type mice, Group S, LDLr-/ - mice fed a standard diet, Group HL, LDLr-/ - mice fed a hyperlipidic diet. After 15 days, blood was collected for analysis of plasma lipids, glucose, insulin, and hematological assays. The HOMA index was calculated to determine insulin resistance. The heart and aorta were removed and histologically processed. Heart sections were immunohistochemically processed with the anti-CD40L antibody to evaluate the inflammatory process. Artery sections were stained with hematoxylin-eosin and picrosirius red to assess morphological and morphometric changes. The S mice were resistant to inflammatory, had a low immunoreactivity to CD40L, high HDL plasma levels, and showed no insulin resistance, even with moderate hyperlipidemia in relation to WT. HL mice exhibited severe hyperlipidemia, increased immunoreactivity to CD40L, marked morphological alterations in the aorta wall, and insulin resistance, all associated with a decrease in HDL plasma levels in relation to S. The results showed a negative association between the plasma levels of high density lipoprotein and the total and differential leukocyte and platelet counts in the LDL receptor gene knockout mice. This ratio showed the important influence of the high density lipoprotein on the modulation of the immune and inflammatory response in dyslipidemias. Therefore, the evaluation of the blood cell count results, routinely correlated with the lipid plasma levels, can be promising in the prevention and prognosis of the severity of pathological conditions involving immune responses in dyslipidemias. The high HDL plasma level is a protective factor against the development of cardiovascular inflammation and insulin resistance in LDLr-/- mice, thus preventing the incidence of neointimal lesions. / Os camundongos LDLr-/- são hiperlipidêmicos espontâneos e resistentes ao desenvolvimento de lesões neointimais. O presente estudo teve como objetivo determinar a influência dos níveis plasmáticos de lipoproteína de alta densidade na inflamação cardiovascular, na resistência insulínica e no hemograma de camundongos knockout para gene do receptor de LDL (LDLr-/-). Foram utilizados 3 grupos experimentais de camundongos machos com 3 meses de idade: Grupo WT, camundongos selvagens; Grupo S, camundongos LDLr-/- que receberam ração padrão; Grupo HL, camundongos LDLr-/- que receberam ração hiperlipídica. Após 15 dias, o sangue foi coletado para análises plasmáticas dos lipídeos, glicose, insulina e para análises hematológicas. O índice de Homa foi calculado para determinar a resistência insulínica. O coração e aorta foram removidos e processados histologicamente. Cortes histológicos do coração foram processados imunoistoquimicamente com anticorpo anti-CD40L para avaliar processo inflamatório. Cortes histológicos das artérias foram corados com hematoxilina/eosina e picrosírius red para avaliar alterações morfológicas e morfométricas. Os camundongos S foram resistentes ao processo inflamatório, caracterizado por baixa imunorreatividade para o CD40L, com níveis plasmáticos de HDL elevados, e não desenvolveram resistência insulínica, mesmo com hiperlipidemia moderada em relação aos WT. Os camundongos HL apresentaram uma hiperlipidemia severa, aumento na imunorreatividade cardíaca para o CD40L, pronunciadas alterações morfológicas na parede da aorta e resistência insulínica, associadas a um decréscimo nos níveis plasmáticos do HDL em relação aos S. Os resultados mostraram uma associação negativa entre os níveis plasmáticos de lipoproteína de alta densidade e as contagens total e diferencial de leucócitos e plaquetas nos camundongos knockout para o gene do receptor de lipoproteína de baixa densidade. Essa relação demonstrou importante influência da lipoproteína de alta densidade na modulação da resposta imunológica e inflamatória na dislipidemia. Portanto, a avaliação dos resultados do hemograma correlacionada com os níveis plasmáticos de lipídeos, rotineiramente, pode ser promissora na prevenção e no prognóstico da severidade de quadros patológicos que envolvam respostas imunológicas nas dislipidemias. O nível plasmático elevado de HDL é o fator protetor contra o desenvolvimento de processos inflamatórios cardiovasculares e resistência insulínica nos camundongos LDLr-/-, impedindo o desenvolvimento das lesões neointimais.

Objective: Atherosclerosis, the main pathology underlying cardiovascular diseases is accelerated in diabetic patients. Genetic mouse models require breeding efforts which are time-consuming and costly. Our aim was to establish a new nongenetic model of inducible metabolic risk factors that mimics hyperlipidemia, hyperglycemia, or both and allows the detection of phenotypic differences dependent on the metabolic stressor(s). Methods and Results: Wild-typemice were injected with gain-of-function PCSK9D377Y (proprotein convertase subtilisin/kexin type 9) mutant adeno-associated viral particles (AAV) and streptozotocin and fed either a high-fat diet (HFD) for 12 or 20 weeks or a high-cholesterol/high-fat diet (Paigen diet, PD) for 8 weeks. To evaluate atherosclerosis, two different vascular sites (aortic sinus and the truncus of the brachiocephalic artery) were examined in the mice. Combined hyperlipidemic and hyperglycemic (HGHCi) mice fed a HFD or PD displayed characteristic features of aggravated atherosclerosis when compared to hyperlipidemia (HCi HFD or PD) mice alone. Atherosclerotic plaques of HGHCi HFD animals were larger, showed a less stable phenotype (measured by the increased necrotic core area, reduced fibrous cap thickness, and less a-SMA-positive area) and had more inflammation (increased plasma IL-1b level, aortic pro-inflammatory gene expression, and MOMA-2-positive cells in the BCA) after 20 weeks of HFD. Differences between the HGHCi and HCi HFD models were confirmed using RNA-seq analysis of aortic tissue, revealing that significantly more genes were dysregulated in mice with combined hyperlipidemia and hyperglycemia than in the hyperlipidemia-only group. The HGHCi-associated genes were related to pathways regulating inflammation (increased Cd68, iNos, and Tnfa expression) and extracellular matrix degradation (Adamts4 and Mmp14). When comparing HFD with PD, the PD aggravated atherosclerosis to a greater extent in mice and showed plaque formation after 8 weeks. Hyperlipidemic and hyperglycemicmice fed a PD (HGHCi PD) showed less collagen (Sirius red) and increased inflammation (CD68-positive cells) within aortic plaques than hyperlipidemic mice (HCi PD). HGHCi-PD mice represent a directly inducible hyperglycemic atherosclerosis model compared with HFD-fed mice, in which atherosclerosis is severe by 8 weeks. Conclusion: We established a nongenetically inducible mouse model allowing comparative analyses of atherosclerosis in HCi and HGHCi conditions and its modification by diet, allowing analyses of multiple metabolic hits in mice.

Bakgrund: Hyperlipidemi är ett medicinskt tillstånd som innebär förhöjda nivåer av kolesteroloch triglycerider i blodet. Det är en komplex interaktion av cellulära och molekylära processersom styr kroppens lipidmetabolism. Faktorer som livsstil, kost och ärftliga faktorer spelar en avgörande roll i dess utveckling. Negativa konsekvenser av obehandlad hyperlipidemi inkluderar risken för ateroskleros, hjärt- och kärlsjukdomar, pankreatit, leversjukdomar, synproblem, njursvikt, metabolt syndrom och kognitiva störningar. Behandling och hantering av hyperlipidemi är nödvändig för att minimera dess påverkan på individens hälsa. Sjuksköterskor spelar en viktig roll i att övervaka och stödja patienter med hyperlipidemi genom att erbjuda rådgivning om livsstilsförändringar, administrera läkemedel och utbilda patienter om vikten av följsamhet av behandlingsplaner för att förebygga allvarliga medicinska komplikationer. Syfte: Att undersöka patienters upplevelser av att behandlas för hyperlipidemi. Metod: En litteraturöversikt där fem kvalitativa samt fem kvantitativa artiklar analyserades. Resultat: Resultatet presenteras i tre huvudteman: “Hantering av hyperlipidemi: diagnos, kommunikation och familjevård”, “Emotionell och fysisk hälsa i hyperlipidemi behandling” och“Hyperlipidemi-behandling: symtom, ekonomiska utmaningar och följsamhet” som är uppdelade i åtta underteman. Konklusion: Effektiv kommunikation och tidig utbildning är avgörande för att stödja patienter och minimera riskerna för kardiovaskulära komplikationer. Egenvård med inslag av rätt kost, regelbunden fysisk aktivitet och hantering av stress är centralt för att hantera hyperlipidemi. Patientcentrerad vård och individuellt stöd från sjuksköterskor är avgörande för att förbättra patienternas hälsa och minska risken för hjärt- och kärlsjukdom. / Background: Hyperlipidemia is a medical condition that involves elevated levels of cholesterol and triglycerides in the blood. It is a complex interaction of cellular and molecular processes that governs the body's lipid metabolism. Factors such as lifestyle, diet and hereditary factors play adecisive role in its development. Adverse consequences of untreated hyperlipidemia include the risk of atherosclerosis, cardiovascular disease, pancreatitis, liver disease, vision problems, kidney failure, metabolic syndrome and cognitive impairment. Treatment and management of hyperlipidemia is necessary to minimize its impact on the individual's health. Nurses play an important role in monitoring and supporting patients with hyperlipidemia by offering advice on lifestyle changes, administering medications, and educating patients on the importance of adherence to treatment plans to prevent serious medical complications. Aim: To investigate patients' experiences of being treated for hyperlipidaemia. Method: A literature review in which five qualitative and five quantitative articles were analyzed. Findings: The results are presented in three main themes: "Management of hyperlipidemia: diagnosis, communication and family care", "Emotional and physical health in hyperlipidemia treatment" and "Hyperlipidemia treatment: symptoms, financial challenges and compliance "which are divided into eight sub-themes. Conclusion: Effective communication and early education are essential to support patients and minimize the risks of cardiovascular complications. Self-care with elements of the right diet, regular physical activity and managing stress is central to handle hyperlipidemia. Patient-centered care and individualized support from nurses are critical to improving patient health and reducing the risk of cardiovascular disease.

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Endothelial cell (EC) activation is a change of the endothelium from a quiescent state to one that is involved in immune reactions. Activation of ECs is associated with the inception of atherosclerosis. Atherosclerosis is a chronic inflammatory disease that involves adaptive and innate immunity. There are many pro-inflammatory stimuli which activate the endothelium. The pro-inflammatory cytokine interleukin-17 (IL-17) has been shown to activate lung microvascular ECs. Enhanced expression of the IL-17 receptor by synovial ECs is associated with rheumatoid arthritis. These studies suggest that IL-17 plays an important role in EC biology. Nevertheless, the role of IL-17 in EC activation and endothelial dysfunction in the context of hyperlipidemia-induced atherosclerosis has not been studied. In the current study, we investigated the role of IL-17 in EC activation in vitro with mouse aortic ECs and human aortic ECs. In addition, we used the IL-17/ApoE double knock-out mouse to determine the role of IL-17 in vessel function and atherosclerosis development. First, we found that hyperlipidemia increased the number of IL-17-producing cells in the spleens from wild type mice and ApoE-/- mice that were fed a Western diet when compared to their respective normal chow diet controls. We also found that after treatment with the pro-atherogenic factor, oxidized LDL, there was an increase in the expression of IL-17 receptor by ECs. Using an EC specific array, we found that IL-17 induced significant up-regulation of four genes that are associated with EC activation in mouse aortic ECs. The four genes induced in IL-17-treated mouse aortic ECs were Cxcl1, Cxcl2, Il6, and Csf2. Moreover, we also found that IL-17 induced these four genes in human aortic ECs, and we showed that enhanced monocyte adhesion to ECs was dependent on these four genes. It was previously observed that a Western diet induced vessel dysfunction in the aortas of ApoE-/- mice. Thus, we sought to determine whether IL-17-deficiency rescues impaired endothelium-dependent relaxation in ApoE-/- mice that were fed a Western diet with the Wire Myograph System. We found that ApoE-/- mice on a 3-week Western diet had impaired endothelium-dependent relaxation when compared to IL-17-/-ApoE-/- mice. Endothelium-independent relaxation in response to sodium nitroprusside (SNP) and contraction responses induced by potassium chloride (KCl) and phenylephrine (PE) were not different in ApoE-/- mice and IL-17-/-ApoE-/- mice. Since our in vitro studies and vessel function assay pointed to a pro-atherogenic role for IL-17, we investigated lesion formation in ApoE-/- mice and IL-17-/-ApoE-/- mice. Lesion formation was assessed with Sudan IV staining of the whole aorta and Oil red O staining of aortic sinus cross sections. IL-17 deficiency in ApoE-/- mice did not affect atherosclerotic lesion formation in our study. Hyperlipidemia is a well-established risk factor for atherosclerosis so we investigated whether the pro-atherogenic role of IL-17 may have been compromised by lipid levels in vivo. The lipid profiles of mice which measured the levels of LDL, HDL, triglyceride, non-esterified free fatty acid, and total cholesterol were determined. The lipid profiles showed that IL-17 deficiency in ApoE-/- mice modulated the levels of the lipids in the plasma. Taken together, our data suggest that IL-17 is up-regulated in hyperlipidemia and IL-17 induces aortic EC activation. IL-17 also contributes to endothelial dysfunction in ApoE-/- mice induced by a Western diet. Moreover, IL-17 may modify lipid metabolism in mice. The effects of IL-17 on lipid levels may weaken its pro-atherogenic potential and contribute to the lack of an atherosclerotic phenotype in our atherosclerosis study. Our current work has shed light on the role of IL-17 on EC biology and has provided insights into the effects of IL-17 on EC activation, lipid modification, and vascular function. These important findings may serve as the stepping stone to the development of therapeutics that target vascular inflammation and its underlying mechanisms. The studies in this dissertation were supported by grants from the National Institutes of Health (NIH) and a fellowship from the American Heart Association (AHA). / Pharmacology

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Submitted by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-02-11T18:44:24Z No. of bitstreams: 2 Dissertação - Silmara da Cunha Pimentel.pdf: 1973075 bytes, checksum: 3b9949f43e0f7b653e8e8ccf7fca49c2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-02-12T12:55:06Z (GMT) No. of bitstreams: 2 Dissertação - Silmara da Cunha Pimentel.pdf: 1973075 bytes, checksum: 3b9949f43e0f7b653e8e8ccf7fca49c2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-02-12T12:55:22Z (GMT) No. of bitstreams: 2 Dissertação - Silmara da Cunha Pimentel.pdf: 1973075 bytes, checksum: 3b9949f43e0f7b653e8e8ccf7fca49c2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2016-02-12T12:55:22Z (GMT). No. of bitstreams: 2 Dissertação - Silmara da Cunha Pimentel.pdf: 1973075 bytes, checksum: 3b9949f43e0f7b653e8e8ccf7fca49c2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-08-03 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / Dyslipidemia is a modification in blood levels of fat, one of the higher incidence of the pathologies in the world population, currently regarded as a public health concern. Some factors contribute greatly to increase cardiovascular diseases; among them, the lipid metabolism is one of most important. This factor is related to ingestion of lipid but the consumption of monounsaturated fatty acid (oleic) show neutral effect over cholesterolemy. However, it has been noticed that high oleic acid diets increase High Density Lipoprotein level (HDL-c) and may reduce the Low Density Lipoprotein level (LDL-c). The objective was to evaluate the Dyslipidemia Reduction Factor and compare the lipid profile and nutrition of the animals treated with the commercial diet supplemented and compare physicochemical fat and oil indexes using extra virgin olive oil and cupuaçu fatty seed. In this comparative study was used experimentally fat of cupuaçu seeds (Theobroma grandiflorum, Schum.) and olive oil (Olea europaea) extra virgin as a food supplementing in Wistar rats male youths. In the experiment were used six groups of eight animals and five of them were induced to dyslipidemia by use of monosodium glutamate. The applicability was 28 days which was provided usual feeding with supplemented of (0.1ml to 0.3ml) of one type of lipid in each group and gas chromatography and physicochemical analysis such as saponification, acidity, peroxide, and free fatty acid levels. So according to the procedures of gavage and oral route there was no difference, however between the lipidogram tests performed, Treatment with fat cupuaçu seed was what achieved the best action of Dyslipidemia Reduction Factor, except for HDL cholesterol that there was no difference in any treatment. Results show that extra virgin olive oil and cupuaçu fatty seed have same fatty acids; although, different amounts for these constituents. These results indicate that different quantities of same fatty acids on different levels may interfere on hipodislipidemic factor for cupuaçu fatty seed diets. / A dislipidemia é uma alteração dos níveis sanguíneos de gordura, uma das patologias com maior incidência na população mundial, considerada atualmente como uma preocupação para a saúde pública. Há fatores que contribuem para o aumento das doenças cardiovasculares, entre estes as dislipidemias, mas o consumo de ácido graxo monoinsaturado (oleico) exerce sobre a colesterolemia um efeito neutro. No entanto, tem se observado que as dietas ricas em ácido oleico aumentam o HDL-c e podem reduzir o nível de LDL-c.. O objetivo foi avaliar o fator hipodislipidêmico e comparar o perfil lipídico e nutricional dos animais tratados com dieta comercial suplementada. e comparar analiticamente os índices físico-químicos de óleos e gorduras de azeite de oliva extra virgem e semente de cupuaçu, respectivamente. Neste estudo comparativo utilizou-se experimentalmente gordura de sementes de cupuaçu (Theobroma grandiflorum) e azeite de oliva (Olea europaea) extra virgem como suplemento alimentar em ratos Wistar jovens do sexo masculino. No experimento foi utilizado seis grupos de oito animais e cinco deles foram induzidos à dislipidemia por uso de glutamato monossódico. A aplicabilidade foi de 28 dias onde foi oferecida alimentação usual com suplementação (0,1ml a 0,3ml) de um tipo de lipídio em cada grupo também foi realizado estudo analítico, por cromatografia gasosa qualitativa e físico-químico de 2 tipos de azeites de oliva extra virgem e dois lotes de gordura de semente do cupuaçu. Portanto de acordo com os procedimentos de gavagem e via oral não houve diferença, porém entre os exames realizados de colesterol total e triglicerídeos, o tratamento com gordura de semente de cupuaçu foi o que obteve a melhor ação hipodislipidêmica, Observou-se que azeite de oliva extra virgem e gordura de semente de cupuaçu possuem o mesmo constituinte químico, porem apresentam picos indicativos de quantidades diferentes Contudo verificou-se que as quantidades diferentes podem ser um indicativo de fator hipodislipidemico também para a gordura de cupuaçu.

Une augmentation de l’activité de la protéine de transfert des esters de cholestérol (CETP) est retrouvée associée à une élévation du développement de l’athérosclérose. L’apolipoprotéine C1 est l’inhibiteur physiologique de la CETP. Ses propriétés électrostatiques jouent un rôle important dans sa capacité d’inhibition de l’activité CETP. Aucune étude de ce potentiel inhibiteur de l’apoC1 n’a été réalisée chez des patients à haut risque cardio-vasculaire ou dyslipidémiques. Nous avons souhaité étudier la fonctionnalité de l’apoC1 par rapport à la CETP chez des patients coronariens normolipidémiques et hyperlipidémiques d’une part et chez des patients diabétiques de type 1 et de type 2 en comparaison à des sujets sains normolipidémiques d’autre part. Nous avons confirmé que l’apoC1 était un inhibiteur physiologique de la CETP chez l’homme normolipidémique. Nous avons montré pour la première fois la perte de cette capacité d’inhibition en cas d’hyperlipidémie chez des sujets coronariens et en cas de diabète de type 1 ou de type 2.En cas d’hyperlipidémie, l’hypertriglycéridémie joue un rôle important en stimulant la réaction de transfert des esters de cholestérol. La possible modification de répartition de l’apoC1 entre HDL et VLDL secondaire à l’hyperlipidémie est probablement également impliquée dans cette perte de fonctionnalité. Au cours du diabète, notamment de type 1, nous avons démontré que l’hyperglycémie, à l’origine du phénomène de glycation, participe, au moins en partie, à cette perte de potentiel inhibiteur. Nous avons également mis en évidence que la glycation in vitro de l’apoC1 modifiait sa charge électrostatique, facteur déterminant de son potentiel inhibiteur. / High cholesteryl ester transfer protein (CETP) activity was found to accelerate the progression of atherosclerosis. Apolipoprotein C1 (apoC1) is a potent physiological inhibitor of CETP. ApoC1 operates as CETP inhibitor through its ability to modify the electrostatic charge at the lipoprotein surface. The inhibitory potential of apoC1 has never been studied in high risk patients or in patients with hyperlipidemia. Our aim was to address the functionality of apoC1 as CETP inhibitor in normo- and hyperlipidemic patients with documented coronary artery disease and in patients with type 1 and type 2 diabetes in comparison with normolipidemic-normoglycemic healthy subjects. We confirmed that apoC1 is a physiological inhibitor of CETP in normolipidemic subjects. We showed for the first time that this inhibitory potential is lost in hyperlipidemic patients with coronary artery disease and in patients with type 1 or type 2 diabetes. During hyperlipidemia, abundant triglyceride-rich lipoproteins, as preferential acceptors of HDL cholesteryl ester, probably drive the CETP-mediated cholesteryl ester transfer reaction. The modified distribution of apoC1 between HDL and VLDL might play a role in this loss of inhibitory property. During diabetes, especially in type 1, we showed that hyperglycemia, responsible for glycation, is involved, at least in part, in this loss of CETP inhibitory ability of apoC1. We also showed that in vitro glycation of apoC1 changed its electrostatic properties, which is recognized as a major determinant of its inhibitory ability.