Diabetic dyslipidaemia

Adiels, Martin; Olofsson, Sven-Olof; Taskinen, Marja‐Riitta; Borén, Jan

doi:10.1097/01.mol.0000226115.97436.c0

Cited by 163 publications

(115 citation statements)

References 75 publications

(44 reference statements)

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this finding, our diabetic baboons have microalbuminuria and also objective changes indicative of diabetic neuropathy. While improved glycaemic control has been shown to prevent diabetes-related microvascular renal and neuropathic complications both in humans with type 1 diabetes mellitus and in animal models of diabetes [1,12,13], it has yet to be determined whether hepatosclerosis can be prevented by intensive glycaemic control. Indeed, this is an important issue for future studies to address.…”

Section: Discussionmentioning

confidence: 99%

“…However, defenestration associated with old age [9] and treatment with a surfactant, poloxamer 407 [27], are associated with impaired transfer of lipoproteins and hypertriacylglycerolaemia. Delayed chylomicron remnant clearance and subsequent post-prandial hypertriacylglycerolaemia are features of type 1 diabetes [10][11][12]; thus it is possible that the substantial loss of fenestrations may contribute to this dyslipidaemia.…”

Section: Discussionmentioning

confidence: 99%

“…This provides a mechanism for age-related impairment in chylomicron remnant clearance and post-prandial hypertriacylglycerolaemia, thus possibly contributing to enhanced vascular risk among older people [4]. As such, there are potential parallels with dyslipidaemia in patients with diabetes mellitus [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis Diabetes mellitus is associated with extensive vascular pathology, yet little is known about its longterm effects on liver sinusoidal endothelial cells (LSECs).Potential diabetic changes in LSECs are important because of the role played by fenestrations in the LSECs in hepatic disposition of lipoproteins. Materials and methods Surgical liver biopsies for electron microscopy and immunohistochemistry were obtained from baboons with long-standing streptozotocin-induced, insulin-treated diabetes mellitus and compared with those from age-matched control animals. Results There was an increase in the thickness of LSECs (170±17 vs 123±10 nm, p<0.01). Fenestrations in LSECs, as determined by overall porosity, were markedly reduced (1.4±0.1% vs 2.6±0.2%, p<0.01). Increased numbers of stellate cells were seen on electron microscopy, and this finding was corroborated by increased smooth muscle actin expression. Diabetes mellitus was also associated with increased endothelial production of von Willebrand factor and caveolin-1. Conclusions/interpretation Diabetes mellitus in the nonhuman primate is associated with marked changes in LSECs, including a reduction in fenestrations. Such changes provide an additional and novel mechanism for impaired hepatic lipoprotein clearance and post-prandial hyperlipidaemia in diabetes mellitus.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The predictive effects of obesity on dyslipidaemia are in keeping with the known effects of increased portal transfer of NEFA to the liver in obesity, causing increased hepatic synthesis of lipoproteins. The consequent increase in triacylglycerol-rich lipoproteins and NEFA flux can accentuate hepatic glucose production, attenuate peripheral glucose uptake, worsen insulin resistance and alter the activities of hormonesensitive lipases, thus setting up a vicious cycle [41].…”

Section: Effects Of Genotypes and Phenotypes On Renal Functionmentioning

confidence: 99%

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Song

Lee

et al. 2009

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis Cardiovascular and renal diseases share common risk factors. We used structural equation modelling (SEM) to evaluate the independent and combined effects of phenotypes and genotypes implicated in cardiovascular diseases on renal function in type 2 diabetes.Methods 1,188 type 2 diabetic patients were stratified into high-risk and low-risk groups according to bimodal distributions of the logarithmically transformed (log e ) urinary albumin:creatinine ratio and plasma creatinine levels. Models for these groups, comprising continuous and non-ranking categorical data, were developed separately to evaluate the inter-relationships among measured variables and latent factors using non-linear SEMs, Bayesian estimation and model selection as assessed by a goodness-of-fit statistic. Results Inter-correlated measured variables (obesity, glycaemia, lipid, blood pressure) and variants of the genes encoding endothelial nitric oxide synthase (NOS), β-adrenergic receptor (ADRB), components of the reninangiotensin system (RAS) and lipid metabolism were loaded onto their respective latent factors of phenotypes and genotypes. In addition to direct and indirect effects, latent factors of obesity, lipid and BP interacted with latent factors of ADRB and RAS genotypes to influence renal function. Together with variants of the genes encoding peroxisome proliferator-activated receptor γ, atrial natriuretic peptide, adducin, G protein β 3 subunit, epithelial sodium channel α subunit and matrix metallopeptidase 3, these parameters explained 39-80% of the variance in renal function in the high-risk and low-risk models. Conclusions/interpretation SEM is a useful tool for confirming and quantifying multiple interactions of biological pathways with genetic determinants. The combined and interactive effects of blood pressure, lipid and obesity on renal function may have therapeutic implications, especially in type 2 diabetic individuals with genetic risk factors.

show abstract

“…This is supported by data from randomized clinical trials and meta‐analyses showing that treatment with statins reduces LDL‐C levels and ASCVD risk in individuals with DM 11, 12, 13. DM is commonly associated with diabetic dyslipidaemia, including elevated triglycerides and reduced levels of high‐density lipoprotein cholesterol (HDL‐C), and with an increased number of small dense LDL particles and apolipoprotein (apo) B‐containing particles, which is thought to contribute to the increased risk level associated with DM 3, 14. Because of this, some guidelines have suggested using non‐HDL‐C, representative of the sum total of all atherogenic cholesterol‐containing particles, as an alternative or secondary treatment target for LDL‐C 8, 9, 15.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Ganda

Plutzky

Sanganalmath

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

AimsIndividuals with both diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) are at very high risk of cardiovascular events. This post‐hoc analysis evaluated efficacy and safety of the PCSK9 inhibitor alirocumab among 984 individuals with DM and ASCVD pooled from 9 ODYSSEY Phase 3 trials.Materials and methodsChanges in low‐density lipoprotein cholesterol (LDL‐C) and other lipids from baseline to Week 24 were analysed (intention‐to‐treat) in four pools by alirocumab dosage (150 mg every 2 weeks [150] or 75 mg with possible increase to 150 mg every 2 weeks [75/150]), control (placebo/ezetimibe) and background statin usage (yes/no).ResultsAt Week 24, LDL‐C changes from baseline in pools with background statins were −61.5% with alirocumab 150 (vs −1.0% with placebo), −46.4% with alirocumab 75/150 (vs +6.3% with placebo) and −48.7% with alirocumab 75/150 (vs −20.6% with ezetimibe), and −54.9% with alirocumab 75/150 (vs +4.0% with ezetimibe) without background statins. A greater proportion of alirocumab recipients achieved LDL‐C < 70 and < 55 mg/dL at Week 24 vs controls. Alirocumab also resulted in significant reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) vs controls. Alirocumab did not appear to affect glycaemia over 78‐104 weeks. Overall safety was similar between treatment groups, with a higher injection‐site reaction frequency (mostly mild) with alirocumab.ConclusionAlirocumab significantly reduced LDL‐C and other atherogenic lipid parameters, and was generally well tolerated in individuals with DM and ASCVD.

show abstract

Diabetic dyslipidaemia

Cited by 163 publications

References 75 publications

Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes

Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Contact Info

Product

Resources

About