Statins and beyond: Concurrent strategies for prevention of cardiovascular disease in patients with type 2 diabetes

Standl, Eberhard

doi:10.1177/1479164112448876

Cited by 7 publications

(4 citation statements)

References 96 publications

(139 reference statements)

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“…Furthermore, cFLC remained independently associated with CVD risk after adjustment for insulin, statins, or ACE inhibitors. Although these treatments have been successful in reducing the risk of CVD in diabetes, the residual risk remained significant and may result from elevated triglyceride levels and chronic inflammation, which have been proposed as additional therapeutic targets (10,11). In this study, a simple risk model including cFLC, SBP, and triglycerides identified the majority of patents suffering CVD events and could therefore be useful in identifying high-risk patients that may benefit from such novel treatments.…”

Section: Discussionmentioning

confidence: 96%

Elevated Serum Free Light Chains Predict Cardiovascular Events in Type 2 Diabetes

Bellary

Faint²,

Assi³

et al. 2014

Diabetes Care

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OBJECTIVEElevated polyclonal serum immunoglobulin free light chains (FLCs; combined FLCk+FLCl [cFLC]) are associated with adverse clinical outcomes and increased mortality; we investigated cFLC and cardiovascular disease (CVD) events in type 2 diabetes. RESEARCH DESIGN AND METHODSIn a cohort study of 352 south Asian patients with type 2 diabetes, serum cFLC, high-sensitivity C-reactive protein (hsCRP), and standard biochemistry were measured. CVD events over 2 years were recorded and assessed using multiple logistic regression. RESULTScFLC levels were elevated significantly in 29 of 352 (8%) patients with CVD events during 2 years of follow-up (50.7 vs. 42.8 mg/L; P = 0.004). In multivariate analysis, elevated cFLC (>57.2 mg/L) was associated with CVD outcomes (odds ratio 3.3 [95% CI 1.3-8.2]; P = 0.012) and remained significant after adjusting for age, albumin-to-creatinine ratio, diabetes duration, or treatment.CONCLUSIONS cFLC elevation is a novel marker for CVD outcomes in type 2 diabetes that warrants further investigation.Predicting risk of cardiovascular disease (CVD) in type 2 diabetes (1-3) using algorithms achieves only moderate performance particularly in different ethnic populations (3). An association between increased polyclonal combined immunoglobulin free light chain (cFLC, summated FLCk+FLCl) concentrations and increased allcause mortality has been reported (4,5); we assessed the potential of cFLC as a marker of CVD outcomes in south Asian patients with type 2 diabetes. RESEARCH DESIGN AND METHODSThe United Kingdom Asian Diabetes Study was a cluster-randomized controlled trial aimed at reducing cardiovascular risk in south Asian patients with type 2 diabetes (6-8). The current study included 352 south Asian patients whose baseline fasting serum samples were available. Detailed clinical history including treatment, CVD history at baseline and over 2 years of follow-up, plus serum biochemistry at baseline (HbA 1c , lipids, and albumin-to-creatinine ratio [ACR]) were obtained. Serum cFLC (Freelite; The Binding Site Group Ltd, Birmingham, U.K.) and hsCRP (Siemens, München, Germany) levels were measured.

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Section: Discussionmentioning

confidence: 96%

Elevated Serum Free Light Chains Predict Cardiovascular Events in Type 2 Diabetes

Bellary

Faint²,

Assi³

et al. 2014

Diabetes Care

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“…Instead, several authors recommended that correction of hyperglycemia should be combined with statin and lifestyle changes ( 151 , 152 ). Around 2012 several reports proposed that therapy with ω 3-fatty acids may treat HTG and may reduce residual risk in T2DM patients and patients with MetS ( 152 , 153 ). By using lifestyle changes, anti-glycemic agents, and lipid-regulating therapies in patients with T2DM, endothelial function improved as well ( 125 ).…”

Section: Residual Risk Factorsmentioning

confidence: 99%

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine

Reijnders,

van der Laarse,

Jukema

et al. 2023

Front. Cardiovasc. Med.

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As time has come to translate trial results into individualized medical diagnosis and therapy, we analyzed how to minimize residual risk of cardiovascular disease (CVD) by reviewing papers on “residual cardiovascular disease risk”. During this review process we found 989 papers that started off with residual CVD risk after initiating statin therapy, continued with papers on residual CVD risk after initiating therapy to increase high-density lipoprotein-cholesterol (HDL-C), followed by papers on residual CVD risk after initiating therapy to decrease triglyceride (TG) levels. Later on, papers dealing with elevated levels of lipoprotein remnants and lipoprotein(a) [Lp(a)] reported new risk factors of residual CVD risk. And as new risk factors are being discovered and new therapies are being tested, residual CVD risk will be reduced further. As we move from CVD risk reduction to improvement of patient management, a paradigm shift from a reductionistic approach towards a holistic approach is required. To that purpose, a personalized treatment dependent on the individual’s CVD risk factors including lipid profile abnormalities should be configured, along the line of P5 medicine for each individual patient, i.e., with Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive approaches.

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“…High blood pressure, hyperglycemia and dislypidemia are held responsible for the increased risk for cardiovascular disease in MetS and T2DM patients, including microvascular complications (including retinopathy, nephropathy and neuropathy) and atherosclerosis at the macrovascular level [ 1 – 4 ]. Both high fasting glucose levels and impaired glucose tolerance are associated with increased cardiovascular events [ 5 ], while impaired glucose tolerance predicts cardiovascular death [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic changes in type 2 diabetes are reflected in peripheral blood cells, revealing aberrant cytotoxicity, a viral signature, and hypoxia inducible factor activity

et al. 2015

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BackgroundMetabolic syndrome (MetS) is characterized by central obesity, insulin resistance, dysglycemia, and a pro-atherogenic plasma lipid profile. MetS creates a high risk for development of type 2 diabetes (T2DM) and cardiovascular disease (CVD), presumably by altering inflammatory responses. Presently, it is unknown how the chronic metabolic disturbances in acute hyperglycemia, MetS and T2DM affect the immune activity of peripheral blood cells.MethodsWe performed genome-wide expression analysis of peripheral blood cells obtained from patients with T2DM (n = 6) and age-, sex- , BMI- and blood pressure-matched obese individuals with MetS (n = 4) and lean healthy normoglycemic controls (n = 3), both under fasting conditions and after controlled induction of acute hyperglycemia during a 70 min hyperglycemic clamp. Differential gene expression during fasting conditions was confirmed by real-time PCR, for which we included additional age-, sex-, BMI-, and blood pressure-matched obese individuals with (n = 4) or without (n = 4) MetS.ResultsPathway and Gene ontology analysis applied to baseline expression profiles of peripheral blood cells from MetS and T2DM patients revealed metabolic changes, highly similar to a reoviral infection gene signature in T2DM patients. Transcription factor binding site analysis indicated that increased HIF-1α activity, a transcription factor induced by either hypoxia or oxidative stress, is responsible for this aberrant metabolic profile in peripheral blood cells from T2DM patients. Acute hyperglycemia in healthy controls resulted in reduced expression of cytotoxicity-related genes, representing NK- and CD8+ cells. In obese controls, MetS and especially T2DM patients, baseline expression of genes involved in cytotoxicity was already low, compared to healthy controls and did not further decrease upon acute hyperglycemia.ConclusionsThe reduced activity of cytotoxic genes in T2DM is explained by chronic hyperglycemia, but its acute effects are restricted to healthy controls. Genome expression of circulating leukocytes from T2DM patients differs from MetS individuals by a specific reovirus signature. Our data thus suggest a role for suppressed anti-viral capacity in the etiology of diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0096-y) contains supplementary material, which is available to authorized users.

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Statins and beyond: Concurrent strategies for prevention of cardiovascular disease in patients with type 2 diabetes

Cited by 7 publications

References 96 publications

Elevated Serum Free Light Chains Predict Cardiovascular Events in Type 2 Diabetes

Elevated Serum Free Light Chains Predict Cardiovascular Events in Type 2 Diabetes

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine

Metabolic changes in type 2 diabetes are reflected in peripheral blood cells, revealing aberrant cytotoxicity, a viral signature, and hypoxia inducible factor activity

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