Vascular disease and diabetes: Is hypoglycemia an aggravating factor?

Department of Diabetes, Royal Infirmary of Edinburgh, UK.
Diabetes/Metabolism Research and Reviews (Impact Factor: 3.55). 07/2008; 24(5):353-63. DOI: 10.1002/dmrr.865
Source: PubMed


Acute hypoglycaemia provokes profound physiological changes affecting the cardiovascular system and several haematological parameters, principally as a consequence of sympatho-adrenal activation and counter-regulatory hormonal secretion. Many of these responses have an important role in protecting the brain from neuroglycopenia, through altering regional blood flow and promoting metabolic changes that will restore blood glucose to normal. In healthy young adults the cardiovascular effects are transient and have no obvious detrimental consequences. However, some of the effected changes are potentially pathophysiological and in people with diabetes who have developed endothelial dysfunction, they may have an adverse impact on a vasculature that is already damaged. The acute haemodynamic and haematological changes may increase the risk of localized tissue ischaemia, and major vascular events can certainly be precipitated by acute hypoglycaemia. These include myocardial and cerebral ischaemia and occasionally infarction. Established diabetic retinopathy often deteriorates after strict glycaemic control is instituted, the latter being associated with a threefold increase in frequency of severe hypoglycaemia, and enhanced exposure to mild hypoglycaemia. The possible mechanisms underlying these hypoglycaemia-induced effects include haemorrheological changes, white cell activation, vasoconstriction, and the release of inflammatory mediators and cytokines. The concept that acute hypoglycaemia could aggravate vascular complications associated with diabetes is discussed in relation to evolving comprehension of the pathogenesis of atherosclerosis and blood vessel disease.

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    • "It has recently been suggested that hypoglycemia may play an important role in vascular complications of diabetes [1]. "
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    ABSTRACT: It has been reported that hyperglycemia following hypoglycemia produces an ischemia-reperfusion-like effect in type 1 diabetes. In this study the possibility that GLP-1 has a protective effect on this phenomenon has been tested. 15 type 1 diabetic patients underwent to five experiments: a period of two hours of hypoglycemia followed by two hours of normo-glycemia or hyperglycemia with the concomitant infusion of GLP-1 or vitamin C or both. At baseline, after 2 and 4 hours, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2alpha, sCAM-1a, IL-6 and flow mediated vasodilation were measured. After 2 h of hypoglycemia, flow mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine and IL-6 significantly increased. While recovering with normoglycemia was accompanied by a significant improvement of endothelial dysfunction, oxidative stress and inflammation, a period of hyperglycemia after hypoglycemia worsens all these parameters. These effects were counterbalanced by GLP-1 and better by vitamin C, while the simultaneous infusion of both almost completely abolished the effect of hyperglycemia post hypoglycemia. This study shows that GLP-1 infusion, during induced hyperglycemia post hypoglycemia, reduces the generation of oxidative stress and inflammation, improving the endothelial dysfunction, in type 1 diabetes. Furthermore, the data support that vitamin C and GLP-1 may have an additive protective effect in such condition.
    Cardiovascular Diabetology 06/2013; 12(1):97. DOI:10.1186/1475-2840-12-97 · 4.02 Impact Factor
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    • "It is of interest that our study confirms that both hyperglycemia and hypoglycemia can be considered equivalent as proatherosclerotic risk factors, and that they seem to work through the same pathways and mainly by generating oxidative stress (1,7). "
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    ABSTRACT: OBJECTIVE Hyperglycemia and hypoglycemia currently are considered risk factors for cardiovascular disease in type 1diabetes. Both acute hyperglycemia and hypoglycemia induce endothelial dysfunction and inflammation, raising the oxidative stress. Glucagon-like peptide 1 (GLP-1) has antioxidant properties, and evidence suggests that it protects endothelial function.RESEARCH DESIGN AND METHODS The effect of both acute hyperglycemia and acute hypoglycemia in type 1 diabetes, with or without the simultaneous infusion of GLP-1, on oxidative stress (plasma nitrotyrosine and plasma 8-iso prostaglandin F2alpha), inflammation (soluble intercellular adhesion molecule-1 and interleukin-6), and endothelial dysfunction has been evaluated.RESULTSBoth hyperglycemia and hypoglycemia acutely induced oxidative stress, inflammation, and endothelial dysfunction. GLP-1 significantly counterbalanced these effects.CONCLUSIONS These results suggest a protective effect of GLP-1 during both hypoglycemia and hyperglycemia in type 1 diabetes.
    Diabetes care 04/2013; 36(8). DOI:10.2337/dc12-2469 · 8.42 Impact Factor
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    • "Although the sample size was very small, the results of the present study highlighted the role of hypoglycemia in vascular endothelial dysfunction. There was no significant difference in the reduction of risk for macrovascular complications between the standard treatment and consolidation treatment groups in the ACCORD study; rather, the total number of deaths was significantly higher [7], and the number of sudden cardiovascular deaths was also higher [8] in patients with severe hypoglycemia. What are the underlying mechanisms of the poor outcome in patients with hypoglycemia? "
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    ABSTRACT: Background: Fluctuations in blood glucose level cause endothelial dysfunction and play a critical role in onset and/or progression of atherosclerosis. We hypothesized that fluctuation in blood glucose levels correlate with vascular endothelial dysfunction and that this relationship can be assessed using common bedside medical devices. Methods: Fluctuations in blood glucose levels were measured over 24 hours by continuous glucose monitoring (CGM) on admission day 2 in 57 patients with type 2 diabetes mellitus. The reactive hyperemia index (RHI), an index of vascular endothelial function, was measured using peripheral arterial tonometry (EndoPAT) on admission day 3. Results: The natural logarithmic-scaled RHI (L_RHI) correlated with SD (r=-0.504; P<0.001), the mean amplitude of glycemic excursions (MAGE) (r=-0.571; P<0.001), mean postprandial glucose excursion (MPPGE) (r=-0.411; P=0.001) and percentage of time ≥ 200 mg/dl (r=-0.292; P=0.028). In 12 patients with hypoglycemia, L_RHI also correlated with the percentage of time at hypoglycemia (r=-0.589; P=0.044). L_RHI did not correlate with HbA1c or fasting plasma glucose levels. Furthermore, L_RHI did not correlate with LDL cholesterol, HDL cholesterol, and triglyceride levels or with systolic and diastolic blood pressures. Finally, multivariate analysis identified MAGE as the only significant determinant of L_RHI. Conclusions: Fluctuations in blood glucose levels play a significant role in vascular endothelial dysfunction in type 2 diabetes.
    Cardiovascular Diabetology 01/2013; 12(1):1. DOI:10.1186/1475-2840-12-1 · 4.02 Impact Factor
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