Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease

Sobel, Burton E.; Frye, Robert L.; Detre, Katherine M.

doi:10.1161/01.cir.0000048897.03553.e4

Cited by 129 publications

(19 citation statements)

References 47 publications

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“…Although white adipose tissue (WAT) plays an important role in mammalian energy homeostasis by preventing lipotoxicity and providing a source of energy in times of need, excess amounts of WAT relates to reduction in the number of mitochondria and inflammation of the tissue (Semple et al 2004, Dahlman et al 2006, subsequently resulting in metabolic dysfunction (Trayhurn & Beattie 2001. Obesity is associated with several serious complications including type 2 diabetes, coronary heart disease, and certain types of cancer and, therefore, significantly increases morbidity risks in those affected (Sobel et al 2003). The current prevalence of obesity most likely resulted from the notable decrease in overall physical activity and increase in consumption of readily available energy-dense foods (Ledikwe et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health

Duivenvoorde¹,

Schothorst²,

Bunschoten³

et al. 2011

Journal of Molecular Endocrinology

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High energy intake and, specifically, high dietary fat intake challenge the mammalian metabolism and correlate with many metabolic disorders such as obesity and diabetes. However, dietary restriction (DR) is known to prevent the development of metabolic disorders. The current western diets are highly enriched in fat, and it is as yet unclear whether DR on a certain high-fat (HF) diet elicits similar beneficial effects on health. In this research, we report that HF-DR improves metabolic health of mice compared with mice receiving the same diet on an ad libitum basis (HF-AL). Already after five weeks of restriction, the serum levels of cholesterol and leptin were significantly decreased in HF-DR mice, whereas their glucose sensitivity and serum adiponectin levels were increased. The body weight and measured serum parameters remained stable in the following 7 weeks of restriction, implying metabolic adaptation. To understand the molecular events associated with this adaptation, we analyzed gene expression in white adipose tissue (WAT) with whole genome microarrays. HF-DR strongly influenced gene expression in WAT; in total, 8643 genes were differentially expressed between both groups of mice, with a major role for genes involved in lipid metabolism and mitochondrial functioning. This was confirmed by quantitative real-time reverse transcription-PCR and substantiated by increase in mitochondrial density in WAT of HF-DR mice. These results provide new insights in the metabolic flexibility of dietary restricted animals and suggest the development of substrate efficiency.

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Section: Introductionmentioning

confidence: 99%

Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health

Duivenvoorde¹,

Schothorst²,

Bunschoten³

et al. 2011

Journal of Molecular Endocrinology

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“…The rationale and design of the BARI 2D trial have been described previously 10, 11. Briefly, the BARI 2D trial randomized 2368 patients with both type 2 diabetes mellitus and SIHD to receive either prompt revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in addition to intensive medical therapy or to intensive medical therapy alone and to receive either IS or IP therapy.…”

Section: Methodsmentioning

confidence: 99%

Increased Hazard of Myocardial Infarction With Insulin‐Provision Therapy in Actively Smoking Patients With Diabetes Mellitus and Stable Ischemic Heart Disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Trial

Khan

Chung

Novak

et al. 2017

JAHA

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BackgroundIn the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision (IP) therapy, as opposed to insulin sensitization (IS) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of IP therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction (MI).Methods and ResultsWe analyzed BARI 2D patients who were active smokers randomized to IP or IS therapy. The primary end point was fatal or nonfatal MI. PAI‐1 (plasminogen activator inhibitor 1) activity was analyzed at 1, 3, and 5 years. Of 295 active smokers, MI occurred in 15.4% randomized to IP and in 6.8% randomized to IS over the 5.3 years (P=0.023). IP therapy was associated with a 3.2‐fold increase in the hazard of MI compared with IS therapy (hazard ratio: 3.23; 95% confidence interval, 1.43–7.28; P=0.005). Baseline PAI‐1 activity (19.0 versus 17.5 Au/mL, P=0.70) was similar in actively smoking patients randomized to IP or IS therapy. However, IP therapy resulted in significantly increased PAI‐1 activity at 1 year (23.0 versus 16.0 Au/mL, P=0.001), 3 years (24.0 versus 18.0 Au/mL, P=0.049), and 5 years (29.0 versus 15.0 Au/mL, P=0.004) compared with IS therapy.ConclusionsAmong diabetic patients with stable ischemic heart disease who were actively smoking, IP therapy was independently associated with a significantly increased hazard of MI. This finding may be explained by higher PAI‐1 activity in active smokers treated with IP therapy.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

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“…97,98 The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was a randomized comparison of myocardial revascularization, either with CABG or PCI, versus optimal medical treatment (OMT) in DM patients with stable CAD considered eligible for either PCI or CABG. 99 Once the most appropriate revascularization technique had been chosen, patients were randomized to OMT alone or to revascularization plus OMT. At 5 years, there were no significant differences in the combined endpoint of death, MI, or stroke between the OMT (12%) and revascularization (12%) arms.…”

Section: Revascularization -Percutaneous Coronary Intervention Versusmentioning

confidence: 99%

Optimal treatment of chronic angina in patients with type 2 diabetes mellitus

Kaur¹,

Sandhu²,

A³

et al. 2014

RRCC

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Type 2 diabetes mellitus (T2DM) trebles the risk of developing coronary artery disease (CAD); once CAD has developed, the risk of acute coronary syndromes (ACS) and clinical risk associated with a coronary event, both double in diabetic patients. Patients with T2DM have more extensive CAD and present at a younger age; therefore, identification and management of chronic angina in these patients presents an opportunity to limit both cardiovascular symptoms and adverse outcomes. This article reviews the role of screening and treatment for chronic angina in patients with T2DM. There is a strong evidence base for modifying lifestyle as a way of reducing adverse cardiovascular outcomes in the diabetic population and this article reviews evidence of lifestyle modification as an important and necessary adjunct to pharmacologic intervention. Management of chronic stable angina is addressed by looking at treatments that reduce ischemic symptoms and those that reduce adverse cardiovascular outcomes. Trials specific to the diabetic population are limited, with information largely obtained from the diabetic subgroup analysis of large intervention trials. The growing diabetic population with increased propensity to cardiovascular disease mandates trials specifically in this patient population. Revascularization in patients with diabetes is associated with more complications than in the non-diabetic population. Recent trials specific to this population suggest surgical revascularization to be associated with better long-term outcomes and therefore, this article reviews the evidence for the optimal mode of revascularization in this population.

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Burgeoning Dilemmas in the Management of Diabetes and Cardiovascular Disease

Cited by 129 publications

References 47 publications

Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health

Dietary restriction of mice on a high-fat diet induces substrate efficiency and improves metabolic health

Increased Hazard of Myocardial Infarction With Insulin‐Provision Therapy in Actively Smoking Patients With Diabetes Mellitus and Stable Ischemic Heart Disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Trial

Optimal treatment of chronic angina in patients with type 2 diabetes mellitus

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