The relationship between glycemic control and plasma vascular endothelial growth factor and endothelin-1 concentration in diabetic patients

Kakizawa, Hideaki; Itoh, Mitsuyasu; Itoh, Yasuto; Imamura, Shigeo; Ishiwata, Yoko; Matsumoto, Takashi; Yamamoto, Keiko; Kato, Takefumi; Ono, Yuka; Nagata, Mutsuko; Hayakawa, Naohiro; Suzuki, Atsushi; Goto, Yoshie; Oda, Naohisa

doi:10.1016/j.metabol.2003.12.002

Cited by 84 publications

(71 citation statements)

References 30 publications

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“…VEGF levels strongly increased with time in patients with prolonged critical illness. In contrast to the effect of glycemic control in patients with diabetes mellitus (25,26) and of insulin infusion in fasting, obese, nondiabetic subjects (27), intensive insulin therapy did not attenuate the critical illnessinduced rise in VEGF levels. This apparent discrepancy is likely explained by the fact that critical illness induces more pronounced insulin resistance than do type 2 diabetes and obesity.…”

Section: Figurementioning

confidence: 58%

Intensive insulin therapy protects the endothelium of critically ill patients

Langouche

Vanhorebeek²,

Vlasselaers³

et al. 2005

Journal of Clinical Investigation

425

245

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The vascular endothelium controls vasomotor tone and microvascular flow and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive, compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure. We hypothesized that strict blood glucose control with insulin during critical illness protects the endothelium, mediating prevention of organ failure and death. In this preplanned subanalysis of a large, randomized controlled study, intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels in patients with prolonged critical illness, which reflects reduced endothelial activation. This effect was not brought about by altered levels of endothelial stimuli, such as cytokines or VEGF, or by upregulation of eNOS. In contrast, prevention of hyperglycemia by intensive insulin therapy suppressed iNOS gene expression in postmortem liver and skeletal muscle, possibly in part via reduced NF-κB activation, and lowered the elevated circulating NO levels in both survivors and nonsurvivors. These effects on the endothelium statistically explained a significant part of the improved patient outcome with intensive insulin therapy. In conclusion, maintaining normoglycemia with intensive insulin therapy during critical illness protects the endothelium, likely in part via inhibition of excessive iNOS-induced NO release, and thereby contributes to prevention of organ failure and death.

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Section: Figurementioning

confidence: 58%

Intensive insulin therapy protects the endothelium of critically ill patients

Langouche

Vanhorebeek²,

Vlasselaers³

et al. 2005

Journal of Clinical Investigation

425

245

View full text Add to dashboard Cite

show abstract

“…VEGF elicits a pronounced angiogenic response in a wide variety of in vivo models. [28][29][30] There is also a strong evidence that VEGF is a survival factor for endothelial cells, both in vitro and in vivo. 31 In this study, we tried to evaluate the relationship between VEGF and different micro-and macrovascular complications of diabetes in a group of type II diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

The role of vascular endothelial growth factor in the progression of diabetic vascular complications

Mahdy

Nada

Hadhoud

et al. 2010

Eye

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“…The Mann-Whitney test was utilised in a post hoc analysis to compare the individual groups. Letters indicate statistical significance between groups (P < 0AE05 [21], suggesting that chronic hyperglycaemia may increase VEGF secretion and that reduction in elevated levels of VEGF may be possible with improved glycaemic control [28]. However, Loebig et al [4] showed a lack of association of VEGF with insulin sensitivity in normal-weight and obese subjects, and VEGF levels remained unchanged in patients with type 1 diabetes after 210 min of hyperglycaemia (12AE0 mM) and normoglycaemic (5AE0 mM) clamps with high (120 mU ⁄ kg ⁄ h) and standard insulin infusions (30 mU ⁄ kg ⁄ h), respectively [29].…”

Section: Controlsmentioning

confidence: 99%

VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia¹

Siervo

Tomatis

Stephan

et al. 2012

Eur J Clin Investigation

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Eur J Clin Invest 2012; 42 (9): 967–973 Abstract Background Increased levels of vascular endothelial growth factor (VEGF) have been observed in patients with metabolic syndrome (MetS). Nitric oxide (NO) formation is reduced in MetS, but its relationship to VEGF production remains poorly defined. We evaluated the association between VEGF/NO synthesis and insulin sensitivity in obese subjects and investigated the secretory response of VEGF to an acute elevation of glucose. Materials and methods Seven healthy normal‐weight subjects, seven obese subjects without MetS and seven obese subjects with MetS were recruited. Anthropometry, body composition and cardiometabolic functions (blood pressure, glucose, insulin, triglycerides, total cholesterol, HDL‐C and VEGF) were measured, and a novel stable isotope method was used to assess in vivo rates of NO production. A frequent sampling intravenous glucose tolerance test was performed to study the dynamics of VEGF release. Results Fasting VEGF levels were significantly higher in the two obese groups compared to the control group (P for trend = 0·02), but the difference was not significant after adjustment for age. Vascular endothelial growth factor levels were associated with systolic blood pressure (ρ = 0·54; P = 0·01) and NO production (ρ = −0·44; P = 0·04). Vascular endothelial growth factor levels increased in response to acute hyperglycaemia in normal‐weight and obese subjects (P < 0·001). Conclusions Vascular endothelial growth factor levels rapidly increase during hyperglycaemia and are inversely related to NO production at steady state. The potential link between the acute secretion of VEGF and atherosclerotic risk in subjects with poorly controlled glycaemia as well as the potential of lowering elevated VEGF levels by increasing NO production and/or availability warrants further investigation.

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The relationship between glycemic control and plasma vascular endothelial growth factor and endothelin-1 concentration in diabetic patients

Cited by 84 publications

References 30 publications

Intensive insulin therapy protects the endothelium of critically ill patients

Intensive insulin therapy protects the endothelium of critically ill patients

The role of vascular endothelial growth factor in the progression of diabetic vascular complications

VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia¹

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The relationship between glycemic control and plasma vascular endothelial growth factor and endothelin-1 concentration in diabetic patients

Cited by 84 publications

References 30 publications

Intensive insulin therapy protects the endothelium of critically ill patients

Intensive insulin therapy protects the endothelium of critically ill patients

The role of vascular endothelial growth factor in the progression of diabetic vascular complications

VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia1

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VEGF is indirectly associated with NO production and acutely increases in response to hyperglycaemia¹