Management of Hypertriglyceridemia in the Diabetic Patient

The hypertriglyceridemia of diabetes can be classified into mild to moderate (triglycerides between 150–499 mg/dL) and severe hypertriglyceridemia (triglycerides ≥500 mg/dL). As in any other individuals with hypertriglyceridemia, secondary causes need to be excluded. The management of severe hypertriglyceridemia (chylomicronemia syndrome) includes aggressive reduction of triglycerides with intravenous insulin, fibrates, omega-3 fatty acids, and/or niacin therapy to avert the risk of pancreatitis. In patients with mild to moderate hypertriglyceridemia, the treatment of choice is statin therapy to achieve the low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) target goals. The evidence base would favor niacin therapy in combination with statin therapy to achieve the goals pertaining to LDL cholesterol and non-HDL cholesterol. The data about the combination of fibrate therapy with statin therapy are disappointing

Adverse effects of statin therapy: perception vs. the evidence - focus on glucose homeostasis, cognitive, renal and hepatic function, haemorrhagic stroke and cataract

Aims: To objectively appraise evidence for possible adverse effects of long-term statin therapy on glucose homeostasis, cognitive, renal and hepatic function, and risk for haemorrhagic stroke or cataract. Methods and results: A literature search covering 2000-2017 was performed. The Panel critically appraised the data and agreed by consensus on the categorization of reported adverse effects. Randomized controlled trials (RCTs) and genetic studies show that statin therapy is associated with a modest increase in the risk of new-onset diabetes mellitus (about one per thousand patient-years), generally defined by laboratory findings (glycated haemoglobin ≥6.5); this risk is significantly higher in the metabolic syndrome or prediabetes. Statin treatment does not adversely affect cognitive function, even at very low levels of low-density lipoprotein cholesterol and is not associated with clinically significant deterioration of renal function, or development of cataract. Transient increases in liver enzymes occur in 0.5-2% of patients taking statins but are not clinically relevant; idiosyncratic liver injury due to statins is very rare and causality difficult to prove. The evidence base does not support an increased risk of haemorrhagic stroke in individuals without cerebrovascular disease; a small increase in risk was suggested by the Stroke Prevention by Aggressive Reduction of Cholesterol Levels study in subjects with prior stroke but has not been confirmed in the substantive evidence base of RCTs, cohort studies and case-control studies. Conclusion: Long-term statin treatment is remarkably safe with a low risk of clinically relevant adverse effects as defined above; statin-associated muscle symptoms were discussed in a previous Consensus Statement. Importantly, the established cardiovascular benefits of statin therapy far outweigh the risk of adverse effects

Association of Genetic Variants Related to CETP Inhibitors and Statins With Lipoprotein Levels and Cardiovascular Risk

Importance: Some cholesteryl ester transfer protein (CETP) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels without reducing cardiovascular events, suggesting that the clinical benefit of lowering LDL-C may depend on how LDL-C is lowered. Objective: To estimate the association between changes in levels of LDL-C (and other lipoproteins) and the risk of cardiovascular events related to variants in the CETP gene, both alone and in combination with variants in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene. Design, Setting, and Participants: Mendelian randomization analyses evaluating the association between CETP and HMGCR scores, changes in lipid and lipoprotein levels, and the risk of cardiovascular events involving 102 837 participants from 14 cohort or case-control studies conducted in North America or the United Kingdom between 1948 and 2012. The associations with cardiovascular events were externally validated in 189 539 participants from 48 studies conducted between 2011 and 2015. Exposures: Differences in mean high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein B (apoB) levels in participants with CETP scores at or above vs below the median. Main Outcomes and Measures: Odds ratio (OR) for major cardiovascular events. Results: The primary analysis included 102 837 participants (mean age, 59.9 years; 58% women) who experienced 13 821 major cardiovascular events. The validation analyses included 189 539 participants (mean age, 58.5 years; 39% women) with 62 240 cases of coronary heart disease (CHD). Considered alone, the CETP score was associated with higher levels of HDL-C, lower LDL-C, concordantly lower apoB, and a corresponding lower risk of major vascular events (OR, 0.946 [95% CI, 0.921-0.972]) that was similar in magnitude to the association between the HMGCR score and risk of major cardiovascular events per unit change in levels of LDL-C (and apoB). When combined with the HMGCR score, the CETP score was associated with the same reduction in LDL-C levels but an attenuated reduction in apoB levels and a corresponding attenuated nonsignificant risk of major cardiovascular events (OR, 0.985 [95% CI, 0.955-1.015]). In external validation analyses, a genetic score consisting of variants with naturally occurring discordance between levels of LDL-C and apoB was associated with a similar risk of CHD per unit change in apoB level (OR, 0.782 [95% CI, 0.720-0.845] vs 0.793 [95% CI, 0.774-0.812]; P = .79 for difference), but a significantly attenuated risk of CHD per unit change in LDL-C level (OR, 0.916 [95% CI, 0.890-0.943] vs 0.831 [95% CI, 0.816-0.847]; P < .001) compared with a genetic score associated with concordant changes in levels of LDL-C and apoB. Conclusions and Relevance: Combined exposure to variants in the genes that encode the targets of CETP inhibitors and statins was associated with discordant reductions in LDL-C and apoB levels and a corresponding risk of cardiovascular events that was proportional to the attenuated reduction in apoB but significantly less than expected per unit change in LDL-C. The clinical benefit of lowering LDL-C levels may therefore depend on the corresponding reduction in apoB-containing lipoprotein particles.Dr Oliver-Williams is supported by Homerton College, University of Cambridge. Dr Butterworth is supported by the European Research Council. Dr Danesh is supported by the Medical Research Council, British Heart Foundation, and the National Institute for Health Research. Dr Davey Smith works within the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_12013/1) and the University of Bristol

Chemical Imaging on Liver Steatosis Using Synchrotron Infrared and ToF-SIMS Microspectroscopies

Fatty liver or steatosis is a frequent histopathological change. It is a precursor for steatohepatitis that may progress to cirrhosis and in some cases to hepatocellular carcinoma. In this study we addressed the in situ composition and distribution of biochemical compounds on tissue sections of steatotic liver using both synchrotron FTIR (Fourier transform infrared) and ToF-SIMS (time of flight secondary ion mass spectrometry) microspectroscopies. FTIR is a vibrational spectroscopy that allows investigating the global biochemical composition and ToF-SIMS lead to identify molecular species in particular lipids. Synchrotron FTIR microspectroscopy demonstrated that bands linked to lipid contribution such as -CH3 and -CH2 as well as esters were highly intense in steatotic vesicles. Moreover, a careful analysis of the -CH2 symmetric and anti-symmetric stretching modes revealed a slight downward shift in spectra recorded inside steatotic vesicles when compared to spectra recorded outside, suggesting a different lipid environment inside the steatotic vesicles. ToF-SIMS analysis of such steatotic vesicles disclosed a selective enrichment in cholesterol as well as in diacylglycerol (DAG) species carrying long alkyl chains. Indeed, DAG C36 species were selectively localized inside the steatotic vesicles whereas DAG C30 species were detected mostly outside. Furthermore, FTIR detected a signal corresponding to olefin (C = C, 3000-3060 cm−1) and revealed a selective localization of unsaturated lipids inside the steatotic vesicles. ToF-SIMS analysis definitely demonstrated that DAG species C30, C32, C34 and C36 carrying at least one unsaturated alkyl chain were selectively concentrated into the steatotic vesicles. On the other hand, investigations performed on the non-steatotic part of the fatty livers have revealed important changes when compared to the normal liver. Although the non-steatotic regions of fatty livers exhibited normal histological aspect, IR spectra demonstrated an increase in the lipid content and ToF-SIMS detected small lipid droplets corresponding most likely to the first steps of lipid accretion

Efficacy and Safety of Alirocumab in Individuals with Diabetes Mellitus:Pooled Analyses from Five Placebo-Controlled Phase 3 Studies

Introduction: Diabetes mellitus (DM) carries an elevated risk for cardiovascular disease. Here, we assessed alirocumab efficacy and safety in people with/without DM from five placebo-controlled phase 3 studies. Methods: Data from up to 78 weeks were analyzed in individuals on maximally tolerated background statin. In three studies, alirocumab 75 mg every 2 weeks (Q2W) was increased to 150 mg Q2W at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥ 70 mg/dL; two studies used alirocumab 150 mg Q2W throughout. The primary endpoint was percentage change in LDL-C from baseline to week 24. Results: In the alirocumab 150 mg pool (n = 2416), baseline LDL-C levels were 117.4 mg/dL (DM) and 130.6 mg/dL (without DM), and in the 75/150 mg pool (n = 1043) 112.8 mg/dL (DM) and 133.0 mg/dL (without DM). In the 150 mg Q2W group, week 24 LDL-C reductions from baseline were observed in persons with DM (− 59.9%; placebo, − 1.4%) and without DM (− 60.6%; placebo, + 1.5%); 77.7% (DM) and 76.8% (without DM) of subjects achieved LDL-C < 70 mg/dL. In the alirocumab 75/150 mg group, 26% (DM) and 36% (without DM) of subjects received dose increase. In this group, week 24 LDL-C levels changed from baseline by − 43.8% (DM; placebo, + 0.3%) and − 49.7% (without DM; placebo, + 5.1%); LDL-C < 70 mg/dL was achieved by 68.3% and 65.8% of individuals, respectively. At week 24, alirocumab was also associated with improved levels of other lipids. Adverse event rates were generally comparable in all groups (79.8–82.0%). Conclusions: Regardless of DM status, alirocumab significantly reduced LDL-C levels; safety was generally similar. Funding Sanofi and Regeneron Pharmaceuticals, Inc. Plain Language Summary Plain language summary available for this article. Electronic supplementary material The online version of this article (10.1007/s13300-018-0439-8) contains supplementary material, which is available to authorized users

Impacto da exposição académica no estado de saúde de estudantes universitários

OBJECTIVE: To assess the impact of academic life on health status of university students. METHODS: Longitudinal study including 154 undergraduate students from the Universidade de Aveiro, Portugal, with at least two years of follow-up observations. Sociodemographic and behavioral characteristics were collected using questionnaires. Students' weight, height, blood pressure, serum glucose, serum lipids and serum homocysteine levels were measured. Regression analysis was performed using linear mixed-effect models, allowing for random effects at the participant level. RESULTS: A higher rate of dyslipidemia (44.0% vs. 28.6%), overweight (16.3% vs. 12.5%) and smoking (19.3% vs. 0.0%) was found among students exposed to the academic life when compared to freshmen. Physical inactivity was about 80%. Total cholesterol, high density lipoprotein-cholesterol (HDL-C), triglycerides, systolic blood pressure, and physical activity levels were significantly associated with gender (p<0.001). Academic exposure was associated with increased low density lipoprotein-cholesterol (LDL-C) levels (about 1.12 times), and marginally with total cholesterol levels (p=0.041). CONCLUSIONS: High education level does not seem to have a protective effect favoring a healthier lifestyle and being enrolled in health-related areas does not seem either to positively affect students' behaviors. Increased risk factors for non-transmissible diseases in university students raise concerns about their well-being. These results should support the implementation of health promotion and prevention programs at universities.OBJETIVO: Avaliar a influência da vida académica na saúde de estudantes universitários. MÉTODOS: Estudo longitudinal envolvendo 154 estudantes de graduação da Universidade de Aveiro, Portugal, por pelo menos dois anos de acompanhamento. Características sociodemográfi cas e comportamentais foram recordados, por meio de questionários. Foram medidos peso, altura,pressão arterial, glicemia, perfil lipídico e os níveis séricos de homocisteína dos alunos. Foi realizada análise de regressão com modelos lineares mistos considerando as medidas repetidas de cada sujeito. RESULTADOS: Estudantes expostos à vida académica, quando comparados àqueles de ingresso recente à universidade apresentaram proporção mais elevada de dislipidemia (44,0% versus 28,6%), sobrepeso (16,3% versus 12,5%) e tabagismo (19,3% versus 0,0%). No geral, foi observada alta proporção de sedentarismo (cerca de 80%). O colesterol total, lipoproteína de alta densidade, triglicérides, pressão arterial sistólica e níveis de atividade física apresentaram associação signifi cativa com o género (p < 0,001). A exposição académica apresentou-se associada com o aumento dos níveis das lipoproteínas de baixa densidade (cerca de 1,12 vezes), e marginalmente com os níveis de colesterol total (p = 0,041). CONCLUSÕES: Nem o alto nível de instrução parece ter papel protetor na adoção de estilo de vida saudável, tampouco o envolvimento com áreas de saúde muda o comportamento dos estudantes. Altas proporções de fatores de risco para doenças não-transmissíveis em jovens universitários podem afetar seu bem-estar. Os resultados podem servir de apoio às universidades no desenvolvimento de programas de prevenção e promoção da saúde

Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women