Use of Insulin to Improve Glycemic Control in Diabetes Mellitus Paresh Dandona & Ajay Chaudhuri & Husam Ghanim & Priya Mohanty Published online: 18 March 2008 # Springer Science + Business Media, LLC 2008 Abstract Background The restoration of normoglycemia ensures the control of diabetic symptoms and reduction in micro- angiopathic complications in type 1 and type 2 diabetes. However, there is no conclusive evidence that intensive glycemic control alone will prevent macrovascular disease, the commonest cause of morbidity and mortality in type 2 diabetes. As atherosclerosis is an inflammatory condition, it is relevant that the two common insulin resistant states of obesity and type 2 diabetes have significant inflammatory processes, which promote atherosclerosis. It is also relevant that glucose has been shown to have profound effects on the endothelial cell, the leukocyte and the platelet. These effects include the induction of acute oxidative and inflammatory stress and a prothrombotic and pro-apoptotic effect following glucose intake. In contrast insulin has been shown to exert several biological effects at physiologically relevant concentrations, in relation to the endothelial cell, the platelet and leucocyte function, which may be cardio- protective and potentially anti-atherosclerotic. Conclusion These findings are of great interest as it is possible that the prevention of macrovascular complications in type 2 diabetes may require the use of those glucose lowering drugs which have additional anti-inflammatory effects in addition to the control of comorbid conditions (hypertension and dyslipidemia) associated with this disease. Results of future clinical trials are awaited to confirm the benefits of this approach in the primary and secondary prevention of macrovascular complications in type 2 diabetes. Key words diabetes mellitus . glycemic control . insulin . inflammation Introduction Several epidemiological studies have shown that fasting hyperinsulinemia predicts cardiovascular events [1]. This was initially interpreted as evidence that insulin is atherogenic. However, since hyperinsulinemia is a reflection of an insulin resistant state, it is now increasingly accepted that insulin resistance rather than hyperinsulinemia is pro-atherogenic. In the past decade, insulin has been shown to exert several biological effects at physiologically relevant con- centrations, in relation to the endothelial cell, the platelet and leucocyte function, which may be cardioprotective and potentially anti-atherosclerotic [2]. These effects include vasodilation through the activation of the NO–cGMP pathway, an anti-inflammatory effect on the endothelial cell and the mononuclear leucocyte, and an anti-platelet/ anti-thrombotic effect. Similarly, glucose also has been shown to have profound effects on the endothelial cell, the leukocyte and the platelet. These effects include the induction of acute oxidative and inflammatory stress following glucose intake [3]. Glucose also exerts a prothrombotic and pro-apoptotic effect [4]. Work carried out during the last decade has also shown that obesity and type 2 diabetes are pro-inflammatory states [5, 6]. Apart from the increase in pro-inflammatory Cardiovasc Drugs Ther (2008) 22:241–251 DOI 10.1007/s10557-008-6101-3 P. Dandona : A. Chaudhuri : H. Ghanim : P. Mohanty Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY 14209, USA P. Dandona Kaleida Health, 3 Gates Circle, Buffalo, NY 14209, USA P. Dandona (*) Diabetes-Endocrinology Center of WNY, 3 Gates Circle, Buffalo, NY 14209, USA e-mail: pdandona@kaleidahealth.org