NEW-ONSET DIABETES AFTER TRANSPLANTATION: 2003 INTERNATIONAL CONSENSUS GUIDELINES1 (2003)

INTRODUCTION Diabetes Mellitus Diabetes mellitus is one of the most common chronic diseases in the world, with an estimated worldwide prevalence of over 176 million in 2000. Furthermore, the prevalence of the disease is expected to increase in the coming years as industrialized societies become older, more obese, and more sedentary, and it is predicted to rise to 370 million by 2030 (1). Acute metabolic complications of diabetes are associated with high mortality rates; in particular, hyperosmolar hyperglycemia (approximately 15%) and ketoacidosis (up to 5%). The prognosis in these conditions is substantially worse in older patients and those with coma or hypotension (2). Following a review of epidemiologic and pathologic evidence, the American Heart Association has also classified diabetes a major independent risk factor for cardiovascular disease (CVD) (3–8). Manifestations of CVD include atherosclerotic coronary heart disease (CHD), heart failure (diabetic cardiomyopathy), myocardial infarction, stroke, and peripheral vascular disease (7). The risk for stroke has been reported to be two to four times higher in patients with diabetes (7,9). Furthermore, patients with diabetes who develop CVD have a worse prognosis for survival than patients with CVD but without diabetes (8–11). In fact, CVD is listed as the cause of death in approximately 65% of patients with diabetes (12). In addition to the risk for macrovascular complications, diabetes is associated with long-term microvascular complications including neuropathy, retinopathy, nephropathy, and erectile dysfunction. Diabetic nephropathy is the most common single cause of end-stage renal disease in the United States and Europe (13). With respect to retinopathy, after 20 years with the condition, almost all individuals with type 1 diabetes and over 60% with type 2 diabetes have a degree of retinopathy that may progress to loss of vision (14). In fact, diabetes is now considered the leading cause of blindness in developed countries, causing 12,000 to 24,000 new cases each year (15,16). New-Onset Diabetes after Transplantation Diabetes and impaired glucose tolerance occurring as a complication of organ transplantation have been recognized for many years. However, incidence figures for new-onset diabetes after transplantation across different studies have ranged between 2% and 53% (17). Precise figures have been difficult to determine because there has been no consensus regarding the definition of the condition and hence different clinical studies have used a variety of diagnostic criteria. Despite the apparently high incidence of new-onset diabetes after transplantation, transplant patients are for hyperglycemia and the condition is it is that of diabetes after transplantation has for the and the of studies that diabetes after transplantation is associated with and and loss In addition to risk studies that may for a degree of the risk for of diabetes after transplantation However, used in the to diabetes and the of have a major risk for the In diabetes is a complication that the survival of the transplant long-term survival of the and the of is that and of patients and the risk for the Furthermore, and of patients who have developed diabetes the long-term of the the of the the the the and the the New-Onset Diabetes after Transplantation is that of these may in or the incidence and of new-onset diabetes mellitus after The of New-Onset Diabetes after Transplantation Diabetes is one of the most long-term complications of transplantation, the condition is clinical that transplant who develop diabetes are risk of complications, including and Furthermore, the chronic hyperglycemia associated with the condition a long-term risk of microvascular and macrovascular The of new-onset diabetes also of in the United States between and has that the of new-onset diabetes after transplantation are between and higher than for those with no diabetes by the of the year and between and higher by the of the year and prevalence of new-onset diabetes after transplantation The prevalence of new-onset diabetes after transplantation has been in the because of the of a definition for the for diabetes after transplantation are glucose or glucose than and clinical include glucose tolerance to determine the incidence of in transplant has to in the reported incidence of the disease The of many studies are also are and the incidence of the risk of diabetes and patients may develop the condition many years The incidence of new-onset diabetes after transplantation in by incidence of diabetes after transplantation for and transplantation studies reported to be the of 2% to 53% (17). In the type of used to of the in with associated with the (17). in a of in the United the incidence of new-onset diabetes after transplantation patients and and of patients of new-onset diabetes with a after transplant with The of patients with a and new-onset diabetes is the Diabetes mellitus after transplantation in the United with of new-onset diabetes after transplantation The of diabetes after transplantation many with type 2 diabetes in that the be individuals may glucose and may be for years Furthermore, hyperglycemia and diabetes are and may without or However, may be in patients to after diabetes after transplantation The of diabetes after transplantation the condition difficult to the of a The of diabetes two patients are risk the and the of patients diabetes over has been by a of in of patients developed diabetes in the after transplantation, but the of cases over leading to and years of and of a are to the incidence of the the of patients diabetes after transplantation by diabetes incidence in renal in years. with survival In patients without the survival of to 60% in the to between and In addition to these survival the mortality has to of these be to death with also for of all have that the of diabetes is associated with impaired long-term and survival in transplant have reported that the of diabetes after transplantation associated with a in survival and with and patients with new-onset diabetes after transplantation have been to have impaired by with years survival also worse in patients with diabetes with with new-onset diabetes an independent of loss The of new-onset diabetes after transplantation has also been to in a incidence of in transplant in the The cause of impaired survival and in transplant with new-onset diabetes after transplantation is The of nephropathy is one because it has been that nephropathy and is associated with a high of failure However, nephropathy years to develop and may for the failure that be associated with the of In transplant an may be that the of is common in transplant with may and survival by The of of may also for failure However, it is also that in these studies the higher incidence of new-onset diabetes and survival In addition to and studies have reported that of diabetes after transplantation long-term survival of transplant have reported In one survival reported to be for patients who developed diabetes after transplantation with for patients without diabetes The survival of transplant diabetes is also reported to be 2 years with those without diabetes survival of transplant with diabetes may also be with In a of transplant of patients developed diabetes after transplantation, and the of diabetes in these patients to be associated with survival with patients has that survival of transplant is by diabetes and new-onset diabetes after transplantation and that the of diabetes in the of years is associated with a high risk of death a in of a of diabetes is the that long-term survival of patients with diabetes who transplantation is to those with transplantation survival of for for The of new-onset diabetes after transplantation has also been to be an independent risk factor for mortality in transplant The studies have to an of diabetes after transplantation survival is but may be to the of patients or in survival in transplant with new-onset diabetes after transplantation with and of diabetes Transplantation with incidence of and associated risk for in transplant with diabetes may the is by the of two studies in transplant have reported that a major complication in with with complications with in the no in mortality between the two all in the with diabetes by with one in the have reported that the of as a cause of death in transplant with diabetes with those with no diabetes In a review of studies in transplant and reported that the incidence of and the mortality the 2 years are higher in patients with new-onset diabetes after transplantation However, the between the of diabetes and mortality is difficult to to the that are with substantially to the of diabetes Diabetes as a risk factor for CVD CVD is the most common cause of death after renal transplantation in the United States The incidence of myocardial is between and times more common in transplant patients than in the is that the incidence of cardiovascular mortality is also higher in transplant than in patients Furthermore, risk for CVD are also risk for chronic In addition to transplant to diabetes after transplantation has a the risk of death cardiovascular heart disease has been to be times higher in transplant with diabetes than in the with times higher than the in transplant without diabetes to years is because CVD is listed as the cause of death in approximately 65% of individuals with diabetes (12). mortality after transplantation in a of transplant one in transplant diabetes to be the most risk factor for disease and peripheral vascular disease In a diabetes mellitus the risk for transplant patients more than 1 year risk of associated with diabetes substantially higher for transplant than for the Heart risk for transplant more than 1 year after that individuals with diabetes in the have an risk for CVD mortality and that the risk of CVD is also substantially higher in transplant who develop diabetes after transplantation with those who develop diabetes The for the risk of CVD mortality and in transplant diabetes after transplantation is and glucose are reported to be independent risk for in the Furthermore, glucose in the are associated with an risk for CVD mortality in apparently to be because of impaired glucose and those who develop diabetes also have an impaired In transplant with diabetes also have an incidence of and are all to to the higher risk for CVD mortality in In of new-onset diabetes after transplantation is associated with impaired long-term and long-term survival of transplant and risk of mortality and associated with CVD of of new-onset diabetes after of New-Onset Diabetes after Transplantation of new-onset diabetes after transplantation in clinical studies The major in the incidence for diabetes after transplantation has been the of consensus regarding the definition and of the of the condition in the are or glucose than or In clinical the most used definition is the of for a definition has in an of the prevalence of diabetes after transplantation because it patients with as as those with hyperglycemia and impaired glucose or impaired glucose tolerance In definition to the long-term of diabetes after transplantation, as it patients with diabetes it between patients with new of disease those with of has been that the American Diabetes Association also be for the of diabetes after transplantation, and that of the in may be the the definition of the condition In it may be to and because these are to be for the of and for the of diabetes of diabetes in the The has diagnostic for diabetes mellitus in with the in that all of diabetes be the in are also in with the by the Diabetes and the American of of have been to the diagnostic and of diabetes over the 20 years. The major and most to the diagnostic include the of glucose for of diabetes than or to to than or to of the glucose for of impaired glucose than or to to than or to The for these to the between the glucose and in individuals high risk for of as microvascular complications, and to and the of a and diabetes The new the of the that with the is in the it is considered that the risk for microvascular complications is in individuals with an than or to Furthermore, the the risk for macrovascular disease to be in individuals with than or to are than of individuals glucose the for diabetes but be considered have also been recognized in the to the diagnostic the of with impaired glucose tolerance or impaired glucose are these individuals have a higher risk for the of diabetes and CVD than the for Diabetes after Transplantation The to a risk for diabetes after transplantation be of in for and in those who may more and there are no risk for diabetes after transplantation, a of have been that to patients to the of the condition of is an in the clinical of patients transplantation and may be used to and the risk of diabetes after of these risk as and are risk may have an and the of risk a in the of transplant may also the have over the two may for in risk factor in the associated with risk for new-onset diabetes after The incidence of diabetes after transplantation to be in older the of a of studies risk of diabetes after transplantation to increase in patients over the of years is also reported to be associated with and survival and In to be a risk factor for the of diabetes after transplantation is that American and have a risk of new-onset diabetes after transplantation than The incidence of new-onset diabetes after transplantation in patients of different may and of (17). with higher of to is reported to be to times more than and has in with of new-onset diabetes after transplantation to 2 diabetes is a condition a of and and studies that may also be in the of new-onset diabetes after transplantation there have been that a of diabetes may be a for the of diabetes after transplantation, with one a increase in the condition in patients with a more heart transplant who developed diabetes to have a of diabetes in with those who of the condition that individuals with a of diabetes be in the of to the of diabetes and The incidence of diabetes after transplantation has been reported to be higher in individuals with the these studies are and of patients be considered as a risk factor for new-onset diabetes after transplantation after transplantation and is associated with and survival is also a risk factor for has been to be associated with the of diabetes after transplantation in most studies However, studies have the between of diabetes and or to be is a risk factor for type 2 diabetes and it is that as or may be more risk for diabetes after transplantation than or The of diabetes after transplantation to be associated with a of Furthermore, new-onset diabetes after transplantation in patients with is associated with an increase in mortality and mortality of diabetes and diabetes after transplantation in patients with and without diabetes mellitus in transplant with and Transplantation with is also a in transplant occurring in to of and is associated with an risk of failure and mortality Furthermore, a has been between and the of diabetes after transplantation, in patients the of transplantation In a and for diabetes after transplantation for patients who transplantation and with and for patients who transplantation, and of with of with be after transplantation, in studies that the risk for diabetes after transplantation have been associated with an incidence of impaired glucose tolerance and diabetes after transplantation With to is reported to be to times more than The of is in of review glucose transplantation, as a glucose between and a glucose between and or may increase the risk of diabetes after The of of metabolic may also be of the condition, the of these is difficult to because of the of organ failure transplantation Transplantation with a as with a may also increase the risk for diabetes after transplantation of for New-Onset Diabetes and that used for a degree of the risk for of diabetes after transplantation However, different in the to The between and the of diabetes after transplantation is The of diabetes in transplant has been reported to be as high as the of to be of are associated with a risk of diabetes after transplantation and a risk of glucose the in transplant patients to 1 year is associated with a in the of to The incidence of diabetes is also to the of In one of transplant who developed new-onset diabetes hyperglycemia 2 of the of patients hyperglycemia to increase the the of new-onset diabetes of after be or the incidence of diabetes has been associated with an risk for may in increase the incidence of diabetes In a of in transplant there a in the of diabetes with patients However, of the patients because of the of of transplant who developed diabetes after transplantation and to or of two of these patients developed and to have also been associated with incidence of diabetes after In a the for diabetes after transplantation in patients with and with and in those who and for risk to be of patients of diabetes after transplant with and without for The of patients with a that diabetes in the with those for The the the of patients with a and of diabetes that patients patients Diabetes mellitus after transplantation in the United with and have been associated with an risk for diabetes after transplantation, clinical studies that is associated with a higher risk of impaired glucose tolerance and diabetes than in of and transplantation In a of studies transplant the risk for diabetes to be to times higher with 1 year after transplantation with high of the after transplantation have been to be a risk factor for the of and new-onset diabetes after transplantation The of with has been in a the incidence of new-onset diabetes and after transplantation that by 2 years the incidence of new-onset diabetes approximately higher in patients than in patients The in the incidence of new-onset diabetes after transplantation 1 year and 2 years for and that patients but those to develop new-onset diabetes in the year Furthermore, the estimated of new-onset diabetes after transplantation by the of each diabetes to the incidence of new-onset to be almost used for with 1 year and 2 years and risk for diabetes after transplantation with and of diabetes and after transplantation in patients or 1 year the incidence of new-onset diabetes in patients than those and of new diabetes mellitus and renal with incidence of diabetes after transplantation reported to be with and with is also a higher of hyperglycemia in transplantation after for for In hyperglycemia the year more common with than higher incidence of diabetes after transplantation has also been reported in transplant for In of these a by and heart transplant studies that the for diabetes after transplantation is four times in patients of patients of across all organ transplant to be to the of The incidence of diabetes after transplantation in has been reported as in transplant with in those The of in 2 years of and of to and of diabetes by with and for New-Onset Diabetes in diabetes has also been in transplant with reported of to In to be associated with an risk for diabetes after The incidence in transplant in the United States is reported to have in of developed the condition between and with 2% to of in the that The incidence considered to be associated with of the for diabetes after transplantation, for hyperglycemia glucose for with In in a of American a transplant between and developed of these However, a has reported a incidence of new-onset diabetes in and after transplantation The incidence of diabetes to be higher in transplant of American Furthermore, diabetes after transplantation is more to be in The incidence of diabetes in transplant is reported to be clinical a of the in the in the of The the in and of New-Onset Diabetes after Transplantation new-onset glucose or new-onset diabetes after transplantation may However, the of to the of hyperglycemia and diabetes for diabetes after transplantation used in clinical of for a to patients with diabetes and between patients with new of disease and those with of the of with or are these individuals have a higher risk for the of diabetes and CVD than the of patients with and diabetes after transplantation is that the complications of the condition be is that the definition and of diabetes after transplantation be the definition of diabetes mellitus and that has been most by the and In each in the of hyperglycemia with metabolic the be by a different The diabetes the that and are associated with an risk for diabetes is a condition of glucose tolerance with a and patients be for the of the condition with to patients with and and of diabetes after of the Despite the of a of have been that to patients to the of diabetes after transplantation of is an in the clinical of patients transplantation and may be used to and the risk of diabetes including of glucose of also be all patients the and In patients be for the metabolic and cardiovascular risk of because individuals have an risk of diabetes and CVD to the by the the of in the United States the metabolic is a has or more of the risk for diabetes after and than in and in of of than in and in of glucose of transplant all patients be of risk of diabetes after transplantation and that is to increase may in and hence may increase be the of an and in a higher of to the of the condition are for those with an risk for new-onset diabetes those with glucose and individuals be for a patients also be that the long-term survival of with and that no in be without of the transplant of The of an be considered for each there is that are more than of an be the diabetes and CVD risk the and risk for diabetes of each and the of each of risk of diabetes is with and with may risk for or individuals of be as as and a in also be for The risk of new-onset diabetes be the risk of a for also be considered to or for the transplant be in all patients the of or who have been with diabetes but have be as individuals are risk for the of In these the of and to the of be of in the after an without of the transplant a of studies in the have that may be more of risk of CVD and mortality than in individuals with Furthermore, the to more individuals with than the for individuals may have the risk of the of may to the of has been in transplant the of be considered in with is to the of in transplant of Diabetes after Transplantation The the and for patients who develop diabetes after transplantation to the of the The for patients are to the of diabetes of and to complications of diabetes of diabetes and with or be and because condition is to be a risk factor for the of diabetes mellitus of the of is a for transplant who are risk of new-onset because has been to glucose tolerance the year after transplantation the of to 1 year is associated with a in the of to The of is also an independent risk factor for the of diabetes after transplantation, with increase in associated with a risk of new-onset diabetes and a risk of glucose However, in be the risk of associated with of in transplant have that to may be in patients who develop diabetes after transplantation In the of in the of patients with new-onset diabetes after all patients with diabetes who to to the in with patients who develop diabetes after transplantation and are to may be considered in patients diabetes is difficult to In of the transplant and and of an for each those high risk for diabetes after In patients be after transplantation, with to patients with glucose and of diabetes after of diabetes after of diabetes mellitus after transplantation of diabetes after transplantation the for the of patients with type 2 diabetes is that glucose in patients with type 1 or type 2 diabetes in of complications In addition to the of patients the and also be who develop diabetes after transplantation also for the of complications, including retinopathy and may also be to for the of the of has been for the transplant with new-onset the who diabetes after transplantation of The of patients with diabetes to in glucose has the to glucose be an of the of all patients or may also be for patients diabetes is by of the for patients with diabetes the of risk all and in each these and of to the and be year in patients because of in in patients with diabetes and the of of in with patients with diabetes after transplantation have to determine or glucose is with the to the Diabetes and to be used in all cases The of the used and the of the transplant patients diabetes it is that is a is to be to long-term complications but may be difficult to in most may be in most patients but may be to are to an risk for long-term complications, and and of The or may be to different for the of diabetes to the of each it is that an of or higher the for for be that is for of new-onset diabetes after transplantation because it is for Furthermore, in patients with or be with because conditions with the and the may be Diabetic The of new-onset diabetes after transplantation many with type 2 diabetes and it is that transplant who develop new-onset diabetes also be risk of the long-term complications of as retinopathy and it is that all patients with new-onset diabetes are for complications, including an and a The of in the is an of nephropathy in patients with type 1 and type 2 and is a for cardiovascular and is an for for vascular disease and in these to cardiovascular risk (13). for is for all patients with diabetes for type 2 diabetes and after years for type 1 to of nephropathy (13). the of has been in transplant may also be considered in transplant who have developed new-onset diabetes to the of However, it be that many transplant have renal and may have without In may be difficult to in with chronic studies are to the of in transplant with new-onset to diabetes after transplantation of patients with diabetes after transplantation a to that for patients with type 2 diabetes and to of patients with of diabetes after of the most for the of patients with and diabetes after transplantation loss and of loss a as has also been to peripheral and in patients with type 2 diabetes the and are as the in the of type 2 with a of diabetes including of glucose glucose is with and is the to has been the be the of of and of also be The of an may be an is the most used a a or a of each of these is associated with and also the and and of common In the of transplant with impaired it is to the of as with and with is associated with an increase in the risk for CVD and are common with with or are more common with is in the of for transplant patients and be may be the of in the for in transplant patients with renal may be because are in patients with renal or and with be that no of have been in patients to is with a single a of with different of be with the of the are used in the of patients with type 2 or or the of of the also be that of these has been in in transplant may be to or to may be a with or without of and is used in patients with type 2 has been in patients with new-onset diabetes after of may be of is or glucose to than and to than after with an than may be in the of a single of glucose be by the addition of or the by be may also be to are with and of be to glucose be to an or for of and of is that of the risk of chronic heart disease in patients with diabetes all patients with new-onset diabetes after transplantation are high risk of it is that patients also in with the for of to of and In patients with In patients with to be also may be the of in patients with including renal transplant have been the of and as of chronic heart disease are of is reported to the of patients with diabetes in the and is associated with an risk of cardiovascular death a of for the of patients with diabetes have that be in patients to for patients with diabetes in the no studies to have the of in patients with new-onset diabetes after transplantation, an may be expected to be of there is studies of with diabetes and in the that or is associated with a in cardiovascular and a of is for patients with new-onset diabetes after transplantation may be with an with addition of to to the In may to a of in renal no are in transplant studies are to the of these in be to the of to the risk of cardiovascular of new-onset diabetes after transplantation The in the of these the of diabetes as a major complication of transplantation and the that may in However, that a of may the of diabetes in Furthermore, and the long-term complications of the have been developed to a definition and of new-onset diabetes after transplantation and to for of the condition that be used to transplant of these in patients risk of diabetes after transplantation that be in the of these be expected to the risk of new-onset diabetes after transplantation and the long-term associated with the condition of diabetes after