Does Elevated Glucose Promote Atherosclerosis? Pros and Cons

Bornfeldt, Karin E.

doi:10.1161/circresaha.116.308873

Cited by 29 publications

(19 citation statements)

References 20 publications

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“…The reduction of plasma volume and BP without increased sympathetic activity are potential mechanism for early and substantial reduction of HF events in patients receiving empagliflozin and canagliflozin . In addition, our findings support role of extraglycaemic mechanism contributing cardiovascular complications in diabetes . These also underlie the importance of multifaceted approach to prevent cardiovascular complication.…”

Section: Discussionsupporting

confidence: 78%

Effects of dapagliflozin vs vildagliptin on cardiometabolic parameters in diabetic patients with coronary artery disease: a randomised study

Phrommintikul

Wongcharoen

Kumfu

et al. 2019

Brit J Clinical Pharma

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Aims: Sodium glucose co-transporter-2 inhibitors have been shown to reduce cardiovascular events and heart failure in type 2 diabetic (T2D) patients with high cardiovascular risk. Dipeptidyl peptidase-4 inhibitors showed neutral effects and may increase risk of heart failure. We aimed to compare cardiometabolic effects of dapagliflozin and vildagliptin in T2D patients with coronary artery disease (CAD).Methods: Forty-nine T2D patients with CAD were randomly assigned to dapagliflozin (n = 25) or vildagliptin (n = 24) for 6 months in a double-blind fashion. Cardiometabolic parameters were collected at baseline and at the end of treatments.Results: Mean age was 63.2 ± 7.9 years (female 46.9%). Baseline characteristics did not differ between two groups. At 6 months, HbA 1C significantly decreased in both dapaglifozin and vildagliptin groups (0.6 ± 1.0% vs 0.8 ± 1.4%, P = 0.22, respectively). There was no difference between the changes in lipid profiles. Body mass index decreased in patients receiving dapagliflozin, whereas it increased in those receiving vildagliptin (−1.27 [95% confidence interval −2.01, −0.53] vs 1.72 [0.72, 2.72] kg, P < 0.001). The reduction in systolic blood pressure and high-sensitivity troponin T was observed in the dapagliflozin group (−9.87 [−18.00, −1.15] mmHg and 2.49 [−4.50, −0.47] pg/mL) but not in vildagliptin group (−1.97 [−9.42, 5.48] mmHg and 1.98 [−0.02, 3.97] pg/mL). The mean haemoglobin increased in the dapagliflozin group, whereas the mean platelet volume increased in the vildagliptin group. There was no significant change in the inflammatory markers in both the groups. Conclusions: The extraglycaemic effects of dapagliflozin and vildagliptin on cardiometabolic parameters in T2D with CAD were different. The more favourable effects Abbreviations: ACS, Acute coronary syndrome; CAD, Coronary artery disease; DPP-4, Dipeptidyl peptidase-4; GLP-1, Glucagon like peptide-1; SGLT2, Sodium glucose co-transporter 2The authors confirm that the PI for this paper is Arintaya Phrommintikul and that she had direct clinical responsibility for patients

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Section: Discussionsupporting

confidence: 78%

Effects of dapagliflozin vs vildagliptin on cardiometabolic parameters in diabetic patients with coronary artery disease: a randomised study

Phrommintikul

Wongcharoen

Kumfu

et al. 2019

Brit J Clinical Pharma

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“…However, the relationship between elevated blood glucose and atherosclerosis of large arteries appears to be less straightforward. Direct pro-atherogenic effects of glucose levels on the cell types typically present in atherosclerotic lesions could not be demonstrated [38]. It remains possible that elevated glucose acts primarily on tissues, including liver or adipose tissue, and the effect on atherosclerotic lesion cells is mediated by altered signaling from these tissues.…”

Section: The Role Of Hyperglycemia and Advanced Glycation End-productmentioning

confidence: 99%

The Diabetes Mellitus–Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation

Poznyak

Grechko

Poggio

et al. 2020

IJMS

692

359

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Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin secretion, insulin action, or both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, and carbohydrates. Atherosclerosis develops as a result of a multistep process ultimately leading to cardiovascular disease associated with high morbidity and mortality. Alteration of lipid metabolism is a risk factor and characteristic feature of atherosclerosis. Possible links between the two chronic disorders depending on altered metabolic pathways have been investigated in numerous studies. It was shown that both types of diabetes mellitus can actually induce atherosclerosis development or further accelerate its progression. Elevated glucose level, dyslipidemia, and other metabolic alterations that accompany the disease development are tightly involved in the pathogenesis of atherosclerosis at almost every step of the atherogenic process. Chronic inflammation is currently considered as one of the key factors in atherosclerosis development and is present starting from the earliest stages of the pathology initiation. It may also be regarded as one of the possible links between atherosclerosis and diabetes mellitus. However, the data available so far do not allow for developing effective anti-inflammatory therapeutic strategies that would stop atherosclerotic lesion progression or induce lesion reduction. In this review, we summarize the main aspects of diabetes mellitus that possibly affect the atherogenic process and its relationship with chronic inflammation. We also discuss the established pathophysiological features that link atherosclerosis and diabetes mellitus, such as oxidative stress, altered protein kinase signaling, and the role of certain miRNA and epigenetic modifications.

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“…However, in type 1 diabetic patients control of glycemia reduced major cardiovascular events [119], several studies conducted in type 2 diabetic patients showed that glycemic control did not result in a reduction of cardiovascular events [126]. This could be due to the fact that type 2 diabetes frequently is associated with other cardiovascular risk factors such as obesity, hypertension, and dyslipidemia, which could mask the beneficial effects of glucose lowering [126,127]. In addition, forcing myeloid cells to increase glucose uptake and glycolysis through overexpression of Glut1 neither resulted in increased atherosclerosis nor did it mimic the effect of diabetes mellitus on myeloid cells in Ldlr À/À mice [128].…”

Section: The Intriguing Link Between Hyperglycemia and Atherosclerosismentioning

confidence: 99%

Macrophage metabolism in atherosclerosis

2017

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A key aspect of atherosclerosis is the maladaptive inflammatory response to lipoprotein accumulation in the artery. The failure to decrease lipid accumulation, to clear apoptotic cells, and to resolve inflammation ultimately leads to macrophage accumulation within the vascular wall [Thorp EB (2010) Apoptosis 15, 1124–1136; Moore K et al. (2013) Nat Rev Immunol 13, 709–721; Moore KJ and Tabas I (2011) Cell 145, 341–355; Ley K et al. (2011) Arterioscler Thromb Vasc Biol 31, 1506–1516]. Several subsets of macrophages are found inside atherosclerotic plaques [Chinetti‐Gbaguidi G et al. (2015) Nat Rev Cardiol 12, 10–17; Leitinger N and Schulman IG (2013) Arterioscler Thromb Vasc Biol 33, 1120–1126; Mantovani A et al. (2009) Arterioscler Thromb Vasc Biol 29, 1419–1423]: Proinflammatory M1‐like macrophages potentially participate in atherosclerosis initiation and progression; M2‐like macrophages are thought to be protective due to their anti‐inflammatory and profibrotic properties, presumably stabilizing the plaque [Chistiakov DA et al. (2015) Int J Cardiol 184, 436–445; Gordon S (2003) Nat Rev Immunol 3, 23–35]; Mox macrophages develop in response to oxidized phospholipids and present a glutathione‐ and potentially redox‐regulating phenotype [Kadl A et al. (2010) Circ Res 107, 737–746]; Mhem macrophages are found in areas of plaque hemorrhage [Boyle JJ et al. (2009) Am J Pathol 174, 1097–1108; Boyle JJ et al. (2012) Circ Res 110, 20–33] where they are involved in heme clearance. Recent evidence suggests that the relative abundance of these macrophage subsets is a better indicator of plaque progression and stability than the total number of lesion macrophages [Chinetti‐Gbaguidi G et al. (2015) Nat Rev Cardiol 12, 10–17]. Over the last few years, findings in the area of immunometabolism established a link between the metabolic state of the different macrophage phenotypes and their functions [O'Neill LAJ and Pearce EJ (2016) J Exp Med 213, 15–23]. However, the effect of metabolic changes in macrophages on atherosclerotic plaque progression and stability is not well understood and an area of intensive study. In this review, we will summarize and critically discuss recent developments in the field of macrophage metabolism in the context of atherosclerosis to guide future investigation in this area.

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Does Elevated Glucose Promote Atherosclerosis? Pros and Cons

Cited by 29 publications

References 20 publications

Effects of dapagliflozin vs vildagliptin on cardiometabolic parameters in diabetic patients with coronary artery disease: a randomised study

Effects of dapagliflozin vs vildagliptin on cardiometabolic parameters in diabetic patients with coronary artery disease: a randomised study

The Diabetes Mellitus–Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation

Macrophage metabolism in atherosclerosis

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