After all, why would the pulmonary vasculature be selectively spared from the effects of diabetes? Competing Interests The authors declare that they have no competing interests.. hypertension (PH) refers to an abnormally elevated blood pressure in the Dexmedetomidine HCl pulmonary blood circulation that can lead to right ventricular (RV) failure and death . Interestingly, PH has been partitioned and separated from other vascular disorders, including systemic hypertension. Therefore, while the role of diabetes mellitus in the pathogenesis of systemic microvascular and macrovascular disease has been appreciated for decades, there has been little evaluation of the potential role that diabetes could have in the pathogenesis of PH. The existing classification of PH does not account for the potential influence of diabetes or other components of the metabolic syndrome, and current treatment is focused on the use of pulmonary vasodilators. Only recently have we begun to understand that not only diabetes may predispose to PH, but also it may fundamentally alter the prognosis in those with PH. Below, we will review the current diagnosis and management of PH, the clinical evidence supporting a role of diabetes in the pathophysiology of PH, the biochemical evidence suggesting a role of local hyperglycemia and insulin resistance in the development of PH, and directions for future research. 2. Current Classification and Treatment of Pulmonary Hypertension Since 1996, there has been a classification system developed by the World Health Business (WHO) and Dexmedetomidine HCl comprising 5 groups . This system has been subject to minor changes over time, but it has remained relatively stable (Table 1). Table 1 Current clinical classification of pulmonary hypertension. 0.001) for the development of PH, even after other components of the metabolic syndrome are controlled for. In addition, an abnormally high percentage of patients are found to have glucose intolerance at the time they are diagnosed with PAH. Four pulmonary hypertension centers have systematically assessed those patients newly diagnosed with pulmonary hypertension for diabetes mellitus [10C12]. When the experiences from these centers are combined, a total of 415 PH patients were evaluated, of whom 107 (26%) experienced diabetes. This correlates with data from the UK and Ireland pulmonary hypertension registry, which found that 23% of PH patients over the age of 50 experienced diabetes . While these studies provide only a snapshot of the PH community, the incidence of diabetes in the PH populace appears to be higher than the incidence of diabetes in the general populace over the age of 45 (19%)  and suggests a connection between diabetes and PH. In those already diagnosed with PH, diabetes appears to have a significant impact on their disease course. It has been well established that current patients with pulmonary hypertension are older (average age 53.1 in the REVEAL cohort)  and have more comorbidities compared with cohorts from your 1980s and Dexmedetomidine HCl 1990s (common age 36 in the NIH cohort) . Not surprisingly, the older PH populace is much more likely ( 0.001) to have diabetes compared with the younger PH populace . There are now several single-center or two-center studies that have found worse survival in patients with PH and diabetes, compared with those PH patients without diabetes. One showed that, at the time a patient is usually diagnosed with PH, hemoglobin A1C less Dexmedetomidine HCl than 5.7 was an independent predictor of survival ( 0.002) . A separate analysis found that patients with PH and diabetes experienced worse survival (hazard ratio 1.7, = 0.04) compared with other PH patients . A third study found that 10-12 months survival was worse in those with diabetes and PH compared with those without diabetes (= 0.04) . While these studies only show an association and cannot show that diabetes prospects to PH and accelerates the disease, they do raise the question why would the presence of diabetes be harmful to those with PH? To answer this question, we will look at existing research that suggests potential involvement of the microvascular blood circulation of the pulmonary arterioles and the right ventricle as related to diabetes. 4. Right Ventricular Failure and Diabetes Mellitus Many clinical studies have shown that this prognosis of patients with PH is dependent on the right ventricle’s ability to tolerate the increased afterload imposed by pulmonary hypertension. In patients with PH, the RV is usually resultantly hypertrophied and enlarged. The hypertrophied RV is usually subject to ischemia, and this ischemia is usually associated with RV dysfunction and prognosis . Ischemia may be related to increased afterload, to increased myocardial density without a compensatory increase in right ventricular angiogenesis, and to RV microvascular injury impairing oxygen delivery. In addition, it has been well documented CDC7L1 that patients with systemic sclerosis have increased right ventricular.