Risk Factors For New-onset Diabetes Research Articles

Influencing factors of new-onset diabetes after a renal transplant and their effects on complications and survival rate.

ObjectiveTo discuss the onset of and relevant risk factors for new-onset diabetes after a transplant (NODAT) in patients who survive more than 1 year after undergoing a renal transplant and the influence of these risk factors on complications and long-term survival.MethodA total of 428 patients who underwent a renal transplant between January 1993 and December 2008 and were not diabetic before surgery were studied. The prevalence rate of and relevant risk factors for postoperative NODAT were analyzed on the basis of fasting plasma glucose (FPG) levels, and differences in postoperative complications and survival rates between patients with and without NODAT were compared.ResultsThe patients in this study were followed up for a mean of 5.65 ± 3.68 years. In total, 87 patients (20.3%) developed NODAT. Patients who converted from treatment with CSA to FK506 had increased prevalence rates of NODAT (P <0.05). Multi-factor analysis indicated that preoperative FPG level (odds ratio [OR] = 1.48), age (OR = 1.10), body mass index (OR = 1.05), hepatitis C virus infection (OR = 2.72), and cadaveric donor kidney (OR = 1.18) were independent risk factors for NODAT (All P <0.05). Compared with the N-NODAT group, the NODAT group had higher prevalence rates (P < 0.05) of postoperative infection, hypertension, and dyslipidemia; in addition, the survival rate and survival time of the 2 groups did not significantly differ.ConclusionAmong the patients who survived more than 1 year after a renal transplant, the prevalence rate of NODAT was 20.32%. Preoperative FPG level, age, body mass index, hepatitis C virus infection, and cadaveric donor kidney were independent risk factors for NODAT. Patients who converted from treatment with CSA to FK506 after a renal transplant had aggravated impairments in glycometabolism. Patients with NODAT were also more vulnerable to postoperative complications such as infection, hypertension, and hyperlipidemia.

Evaluation of Glucose Metabolism After Distal Pancreatectomy According to the Donor Criteria of the Living Donor Pancreas Transplantation Guidelines Proposed by the Japanese Pancreas and Islet Transplantation Association

BackgroundLiving donor pancreas transplantation (LDPT) reduces the number of deaths of diabetic patients on dialysis and of candidates on the waiting lists and helps to overcome the organ shortage. Stringent criteria must be applied to minimize the risk of metabolic complications for living donors. The Japanese Pancreas and Islet Transplantation Association (JPITA) proposed LDPT guidelines in 2010. In this study, we retrospectively evaluated glucose metabolism of the patients who underwent distal pancreatectomy (DP) according to the donor criteria of the LDPT guidelines proposed by the JPITA. MethodsFifty-two nondiabetic patients who underwent DP were divided into 2 groups according to the donor criteria: indication group (IG, n = 14) who had age ≤ 65, hemoglobin A1c (HbA1c) < 5.9%, and body mass index (BMI) < 25 kg/m2. The other patients were placed in the no indication group (NG, n = 38). Clinical data and percent resected volume (PRV) of each pancreas as determined by multi–detector row computed tomography volumetry were compared between the 2 groups. ResultsDuring the follow-up period (median 12 months), 14 patients (27%) developed new-onset diabetes within a median onset time of 10 months (range 3–24 months) postoperatively. No patient in the IG developed new-onset diabetes. On the other hand, 37% of the patients in the NG developed new-onset diabetes. There were significant between-group differences in changes in preoperative serum fasting glucose and HbA1c levels, whereas there were no significant between-group differences in preoperative serum albumin or body weight. Multivariate analysis identified preoperative HbA1c (odds ratio 51.6, P = .002) and PRV (odds ratio 2.07, P = .033) as independent risk factors for new-onset diabetes. ConclusionLiving donor criteria in the LDPT guidelines proposed by the JPITA are appropriate for prevention of glucose metabolic complications in donors. Further long-term follow-up studies of living donors' metabolic function are needed to clarify the safety of the donor.

Lower magnesium level associated with new-onset diabetes and pre-diabetes after kidney transplantation

Hypomagnesemia is associated with increased peripheral insulin resistance in the general population. It is frequently seen after renal transplantation. We examined its role as a risk factor for new-onset diabetes after transplantation (NODAT) and new-onset pre-diabetes after transplantation (NOPDAT). A retrospective analysis of 138 previously non-diabetic renal transplant recipients was conducted. Cox and logistic regression analyses were performed to examine the associations between 1-month post-transplant serum magnesium level and subsequent diagnoses of NODAT/NOPDAT. NODAT was diagnosed in 34 (24.6 %) and NOPDAT in 12 (8.7 %) patients. Median time to diagnosis of NODAT/NOPDAT was 20.4 months (interquartile range [IQR] 6.8-34.8). Median follow up for the entire group was 3.5 years (IQR 2.3-5.6). Mean magnesium level at 1 month after transplantation was significantly lower in patients subsequently diagnosed with NODAT/NOPDAT (1.60 ± 0.27 vs. 1.76 ± 0.29 mg/dl, p = 0.002). Cox regression analysis identified a trend towards developing NODAT/NOPDAT with lower baseline magnesium levels (hazard ratio 0.89 per 0.1 mg/dl increment in magnesium level, 95 % confidence interval [CI] = 0.78-1.01, p = 0.07); a stronger relationship between the two variables was seen at logistic regression analysis (odds ratio 0.81 per 0.1 mg/dl increment in serum magnesium (95 % CI 0.67-0.98, p = 0.03). A lower magnesium level at 1 month after transplantation may be predictive of a subsequent diagnosis of glucose intolerance or diabetes in renal transplant recipients. Whether replenishing magnesium stores can prevent development of these disorders requires further investigation.

Insulin Resistance as a Risk Factor for New-Onset Diabetes After Kidney Transplantation

IntroductionNew-onset diabetes after transplantation (NODAT) is a serious and common complication after kidney transplantation. Insulin resistance, together with β-cell dysfunction, plays an essential role in the development of diabetes. Homeostasis model assessment of insulin resistance (HOMA-IR), which is calculated as [fasting plasma glucose (mmol/L) × fasting insulin (mU/L)]/22.5, is widely used as an index of insulin resistance. However, the correlation between pretransplant HOMA-IR and the development of NODAT has not been fully established. MethodsWe performed a retrospective study of 44 nondiabetic patients who underwent living donor kidney transplantation in our hospital from July 2006 to October 2009. We compared the HOMA-IR and demographic variables of patients who developed NODAT with those who did not. ResultsFive patients (11.4%) developed NODAT within 3 years after transplantation. There were no differences in demographic variables between patients who developed NODAT and those who did not. Logistic regression analysis revealed that HOMA-IR was a predictive factor of NODAT (odds ratio, 2.88; 95% CI, 1.11–9.59; P < .05). ConclusionsOur results indicate that high HOMA-IR might be an important predictive factor for NODAT. These findings underline the importance of routine pretransplant measurements of fasting plasma glucose and serum insulin for evaluating HOMA-IR.

Genotypes of renin-angiotensin system and plasma adiponectin concentration in kidney transplant patients

Low plasma adiponectin concentration was recently recognized as a novel risk factor for new-onset diabetes after transplantation. Pharmacological modulation of the renin-angiotensin system activity and genetic predisposition were shown to have an influence on plasma adiponectin level. Therefore the aim of this study is to analyze the association between angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT1R) A1166C and angiotensinogen (AGT) M235T genotypes and plasma adiponectin concentration as well as insulin resistance in a cohort of kidney transplant patients. AGT M235T, ACE I/D and AT1R A1166C genotyping and plasma adiponectin and insulin concentrations assessment were performed in 372 patients with functioning kidney allograft (eGFR >20 ml/min/1.73 m2) from 2 transplant centres. Females with II ACE I/D genotype had a significantly higher plasma adiponectin concentration than the ID+DD subgroup, which could partially be explained by a lower BMI in the II subgroup. Males with TT genotype of the AGT M235T gene polymorphism (and higher BMI) had higher plasma concentration of insulin and HOMAIR values than those in the MT+MM subgroup. A multiple regression analysis revealed that only female sex (b=0.239), BMI (b=–0.208) and ACE II genotype (b=0.129) were significantly associated with plasma adiponectin concentration variability. A similar analysis for HOMA-IR showed that its variability was associated with BMI (b=0.333), eGFR (b=–0.115) and plasma adiponectin concentration (b=–0.064) irrespective of any of the analyzed genotypes. Plasma adiponectin concentration, but not insulin resistance, seems to be modulated only by ACE I/D polymorphism in kidney transplant patients. Polymorphisms of the other renin-angiotensin system components do not influence plasma adiponectin concentration or insulin resistance in these patients.

Pancreatic Volumetric Assessment as a Predictor of New-Onset Diabetes Following Distal Pancreatectomy

IntroductionPancreatogenic diabetes after pancreatectomy is of growing importance due to the increasing life expectancy of pancreatectomized patients. Although reduction of pancreatic volume is thought to affect glucose metabolism, a consistent relationship has yet to be determined. This study aimed to investigate functional consequences of distal pancreatectomy (DP) in preoperatively non-diabetic patients. MethodsThis study included 61 non-diabetic patients who underwent DP. Clinical data were obtained, and the percent resected volume (PRV) of each pancreas was determined via multi-detector row computed tomography volumetry. ResultsDuring the follow-up period (median 26 months), 22 patients (36 %) developed new-onset diabetes within a median onset time of 8 months (range 0.5–42 months) postoperatively. The remaining 39 patients also showed impaired glucose metabolism. Multivariate analysis identified preoperative hemoglobin A1c ≥ 5.7 % (odds ratio 15.6, p = 0.001) and PRV > 44 % (odds ratio 11.3, p = 0.004) as independent risk factors for new-onset diabetes. ConclusionsKey determinants of postoperative glycemic control include preoperative functional reserve of the endocrine pancreas and the volume reduction of pancreatic parenchyma. Our findings enable reliable preoperative evaluation of the risk of postoperative diabetes and appropriate postoperative surveillance, which is helpful for early intervention in high risk patients.

Risk Factors and Outcomes of New-Onset Diabetes After Transplant: Single-Centre Experience

We sought to study the prevalence, risk factors, and long-term prognosis of posttransplant diabetes mellitus. We studied all patients with end-stage renal disease without diabetic nephropathy who received a kidney transplant and were followed-up at our center since 1983 (n=218; age, 44.3 ± 13.1 y). Patients with new-onset diabetes after transplant were compared to kidney transplant recipients without risk factors for diabetes mellitus. Patients with new-onset diabetes after transplant were divided into subgroups according to time of onset (early; < 90 d vs late, ≥ 90 d). In total, 73/218 patients (33%) developed new-onset diabetes after transplant. Patients with new-onset diabetes after transplant were significantly older (51.2 ± 11.4 vs 40.7 ± 12.5 y; P < .001) and had a tendency to have a higher body mass index (29.6 ± 8.7 vs 21.6 ± 7.8 kg/m2; P =.05) than those that did not have new-onset diabetes after transplant. In multivariate analysis, age (P < .001), hepatitis C virus infection (P < .05), family history of diabetes mellitus (P < .03), and tacrolimus use (P < .001) were independent risk factors. Five- and 10-year death censored patient survival rates were worse in those that had new-onset diabetes after transplant compared with controls (log rank, 0.04), whereas there was no difference in outcomes between the early and late subgroups. The prevalence of new-onset diabetes after transplant was 33%. Age, body weight at time of transplant, tacrolimus use, family history of diabetes mellitus, and hepatitis C virus infection are independent risk factors for new-onset diabetes after transplant. New-onset diabetes after transplant has a negative effect on patient survival, irrespective of the time of onset and duration of diabetes.

Renal resistive index as a new independent risk factor for new-onset diabetes mellitus after kidney transplantation

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09), P<0.0001]. RI >0.75 (vs. 0≤0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001] and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High RI early after renal transplantation is a long-term risk factor for NODAT, and could be used to refine the individual risk of NODAT.

Genetic and Clinical Risk Factors of New-Onset Diabetes After Transplantation in Hispanic Kidney Transplant Recipients

New-onset diabetes after transplantation (NODAT) is one of the major complications after transplantation and is associated with reduced overall patient and graft survival. The objective of this study was to determine the genetic and clinical risk factors for NODAT in Hispanic kidney transplant recipients. Hispanic kidney allograft recipients without evidence of preexisting diabetes who developed NODAT (n=133) were studied using Hispanic kidney transplant recipients with no evidence of diabetes as a control group (n=170). NODAT was defined as fasting glucose levels ≥126 mg/dL on two or more occasions or patients taking any insulin or oral hypoglycemic agents 1 month or later after kidney transplantation. Fourteen alleles in nine genes were genotyped and other patients' clinical data with genotype data were analyzed by logistic regression. Among 14 alleles, hepatocyte nuclear factor 4 alpha (HNF4A) AA (rs2144908, odds ratio [OR]=1.96, confidence interval [CI]=1.08-3.50, P=0.010), HNF4A TT (rs1884614, OR=2.44, CI=1.42-4.48, P=0.002), and insulin receptor substrate 1 AA+AG (rs1801278, OR=2.71, CI=1.16-6.89, P=0.021) remained significant after logistic regression. Among the clinical factors, average age (OR=1.01, CI=1.00-1.08, P=0.048), sirolimus (OR=5.36, CI=3.02-10.4, P=0.001), deceased donor (OR=1.96, CI=1.16-2.94, P=0.015), and acute rejection (OR=2.92, CI=1.31-5.77, P=0.009) remained significant after logistic regression. This study indicates that polymorphism of two alleles of HNF-4A gene (rs2144908 and rs1884614) and insulin receptor substrate 1 (rs1801278) are significantly associated with NODAT in kidney transplant patients with Hispanic ethnicity. In the case of clinical factors, older age (>50 year), deceased donor type, acute rejection, and sirolimus use are associated with NODAT in Hispanic kidney transplant recipients.

Functional and Histopathologic Changes in Renal Transplant Patients With New-Onset Diabetes and Dyslipidemia

Background The principal risk factors for cardiovascular mortality posttransplantation are hyperglycemia, hypertriglyceridemia, obesity, and smoking. Methods Among 115 patients, we assessed the risk factors for new-onset diabetes (NODM) and dyslipidemia (NODL), and their effects on the function and histopathologic changes in the allografts at 1 year posttransplantation. Results When evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal vs NODM patients ( P = .004), normal versus NODL patients ( P = .002), and normal versus NODL + NODM patients ( P = .0001). The difference in body mass index (BMI) was significant when comparing normal with NODM + NODL patients ( P = .003). In regard to immunosuppressive therapy, NODM was significantly more frequent among/prescribed tacrolimus (tac; P = .005), whereas subjects who received cyclosporine (CsA) showed a significantly higher incidence of NODL ( P = .001). The triglyceride levels were 3.02 ± 1.51 mmol/L among those on CsA versus 2.15 ± 1.57 mmol/L for ( P = .004). The difference also proved to be significant for total cholesterol level: 5.43 ± 1.23 mmol/L versus 4.42 ± 1.31 mmol/L respectively ( P = .001). In regard to allograft function a significant difference was noted at 1 year after transplantation between the NODM + NODL and the normal group in serum creatinine level ( P = .02) as well as the estimated glomerular filtration rate ( P = .004). Among diabetic patients, the serum creatinine level measured at posttransplant year 5 was significantly higher than that in 1 year (212.43 vs 147.00 μmol/L; P = .0003). When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy in all 3 groups compared with normal function patients. Conclusion Our clinical study suggested that at 1 year after transplantation allograft function is already impaired in the presence of both medical conditions (NODM and NODL). However, in regard to morphology, a single condition (NODM or NODL) was sufficient to produce histologic changes in the kidney.

Risk factors for new-onset diabetes after kidney transplantation

New-onset diabetes after transplantation, a common complication following kidney transplantation, is associated with adverse patient and graft outcomes. Our understanding of the risk factors associated with this metabolic disorder is improving and both transplantation-specific and nonspecific factors are clearly involved. Knowledge of these risk factors is important so that clinicians can implement pre-emptive risk stratification strategies and to guide therapeutic, risk-attenuation approaches in patients who develop transplant-associated hyperglycemia. In this Review, we explore the current understanding of the diverse range of risk factors that contribute to abnormal glucose metabolism after transplantation, with the aim of helping to guide clinical decision-making using appropriate risk stratification.

New-onset diabetes after transplantation in tacrolimus-treated, living kidney transplantation: long-term impact and utility of the pre-transplant OGTT

BackgroundTo evaluate the role of the oral glucose tolerance test (OGTT) before transplantation and to examine the risk factors for new-onset diabetes after transplantation (NODAT) during long-term follow-up of renal transplant recipients receiving FK-based therapy.MethodsThe study evaluated 378 patients pre-transplantation using the OGTT and assigned them to one of three groups: Group 1, normal pattern; Group 2, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) pattern (IFG/IGT); and Group 3, DM pattern.ResultsAlthough the incidence of NODAT was higher in Group 3 than in groups 1 and 2, no significant difference was found between the three groups with regard to graft survival during long-term follow-up. Multivariate analysis showed that only a family history of diabetes was a significant factor determining NODAT progression.ConclusionsImpaired glucose tolerance appears to be a threshold influencing NODAT; however, it was not a significant factor in graft survival. Careful monitoring and management based on the result of the pre-transplantation OGTT appear to prevent the deterioration of impaired glucose tolerance in renal transplant recipients receiving FK-based therapy, even when a pre-operative OGTT shows impaired glycemic control.

Early Pulse Pressure and Low-Grade Proteinuria as Independent Long-Term Risk Factors for New-Onset Diabetes Mellitus After Kidney Transplantation

Risk factors for new-onset diabetes after transplantation (NODAT) need to be assessed in large cohorts. We retrospectively evaluated the impact of early (3 and 6 months after transplantation) proteinuria, urinary albumin excretion (UAE) and arterial pressure on NODAT in 828 Caucasian renal transplant recipients (median follow-up: 5.3 years; 5832 patient-years). The 10- and 20-year incidence of NODAT was 15.0% and 22.0%, respectively. Low-grade (<1 g/day) (HR: 2.04 [1.25-3.33], p = 0.0042) and very low-grade (<0.3 g/day) (HR: 2.21 [1.32-3.70], p = 0.0025) proteinuria were independent risk factors for NODAT. There was a dose-dependent relationship across UAE categories (increasing risk from normoalbuminuria to macroalbuminuria) with NODAT. Tacrolimus, sirolimus and beta-blockers (HR: 1.86 [1.07-3.22], p = 0.0277) were significantly associated with NODAT even after multiple adjustments, but not diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Systolic arterial pressure (HR per 10 mmHg: 1.16 [1.03-1.29], p = 0.0126) and pulse pressure (HR: 1.26 [1.12-1.43], p = 0.0002) were associated with NODAT. Only pulse pressure remained significant after adjustments. Patients at highest risks had early proteinuria and pulse pressure >60 mmHg. Early low-grade proteinuria and pulse pressure (in addition to beta-blockers) constitute independent risk factors for NODAT; they may be markers of the metabolic syndrome and/or vascular damage in renal transplant recipients.

Incidence and Risk Factors for New-Onset Diabetes in HIV-Infected Patients

OBJECTIVE—The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated with the onset of diabetes, and to identify possible mechanisms for any relationships found. RESEARCH DESIGN AND METHODS—D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes and exposure to cART after adjusting for known risk factors for diabetes, CD4 count, lipids, and lipodystrophy. RESULTS—Over 130,151 person-years of follow-up (PYFU), diabetes was diagnosed in 744 patients (incidence rate of 5.72 per 1,000 PYFU [95% CI 5.31–6.13]). The incidence of diabetes increased with cumulative exposure to cART, an association that remained significant after adjustment for potential risk factors for diabetes. The strongest relationship with diabetes was exposure to stavudine; exposures to zidovudine and didanosine were also associated with an increased risk of diabetes. Time-updated measurements of total cholesterol, HDL cholesterol, and triglycerides were all associated with diabetes. Adjusting for each of these variables separately reduced the relationship between cART and diabetes slightly. Although lipodystrophy was significantly associated with diabetes, adjustment for this did not modify the relationship between cART and diabetes. CONCLUSION—Stavudine and zidovudine are significantly associated with diabetes after adjustment for risk factors for diabetes and lipids. Adjustment for lipodystrophy did not modify the relationship, suggesting that the two thymidine analogs probably directly contribute to insulin resistance, potentially through mitochondrial toxicity.

Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors

Individuals with diabetes are at higher risk of myocardial infarction than non-diabetics. However, much less is known about the incidence of, and risk factors for, development of diabetes and impaired fasting glucose in patients who have had a myocardial infarction. We set out to estimate this incidence and investigate whether lifestyle factors such as dietary habits might alter this risk. We used prospectively obtained data for 8291 Italian patients with a myocardial infarction within the previous 3 months, who were free of diabetes (determined by medication use, a physician-reported diagnosis, or fasting glucose > or =7 mmol/L) at baseline. Incidence of new-onset diabetes (new diabetes medication or fasting glucose > or =7 mmol/L) and impaired fasting glucose (fasting glucose > or =6.1 mmol/L and <7 mmol/L) were assessed at follow-up at 0.5, 1.0, 1.5, 2.5, and 3.5 years. Baseline data for body-mass index (BMI), other risk factors, dietary habits, and medications were updated during follow-up. A Mediterranean diet score was assigned according to consumption of cooked and raw vegetables, fruit, fish, and olive oil. Associations of demographic, clinical, and lifestyle risk-factors with incidence of diabetes and impaired fasting glucose were assessed with multivariable Cox proportional hazards. During 26 795 person-years (mean follow-up 3.2 years [SD 0.9]), 998 individuals (12%) developed new-onset diabetes (incidence 37 cases per 1000 person-years). Of the 7533 without impaired fasting glucose at baseline, 2514 (33%) developed new-onset impaired fasting glucose or diabetes (incidence 123 cases per 1000 person-years), rising to 3859 (62%) of 6229 with the lower cutoff for impaired fasting glucose of 5.6 mmol/L (incidence 321 cases per 1000 person-years). Independent risk factors for new-onset diabetes or impaired fasting glucose included older age, hypertension, use of beta-blockers, lipid-lowering medications (protective), and diuretic use. Independent lifestyle risk-factors included higher BMI, greater BMI gain during follow-up, current smoking, a lower Mediterranean dietary score, and wine consumption of more than 1 L/day. Data for physical activity were unavailable, but inability to perform exercise testing was associated with higher incidence of diabetes and impaired fasting glucose. Compared with population-based cohorts, patients with a recent myocardial infarction had a higher annual incidence rate of impaired fasting glucose (1.8 vs 27.5% in our study) and diabetes (0.8-1.6% compared with 3.7%) in this study. Thus, our results indicate that myocardial infarction could be a prediabetes risk equivalent. Smoking cessation, prevention of weight gain, and consumption of typical Mediterranean foods might lower this risk, which emphasises the need for guidance on diet and other lifestyle factors for patients who have had a myocardial infarction.

Polycystic Kidney Disease Is a Risk Factor for New-Onset Diabetes After Transplantation

Data from matched historical cohort studies suggest that autosomal-dominant polycystic kidney disease (ADPKD) may be a risk factor for new-onset diabetes after transplantation (NODAT). A retrospective study of 429 renal allografts transplanted from 1990 through 2004 in nondiabetic patients was performed. A multivariate analysis of risk factors for NODAT was performed with focus on ADPKD. A total of 6.5% of all patients developed NODAT and a further 11% developed impaired glucose tolerance. NODAT developed in 13.4% of patients with ADPKD compared with 5.2% of non-ADPKD patients (P=0.01). There were significant univariate associations between NODAT and recipient age (P=0.001) and weight (P<0.0001). There was no association between NODAT and recipient gender, human leukocyte antigen mismatch, acute rejection, or cumulative methylprednisolone dose. In a multivariate analysis, ADPKD was a strong risk factor for the development of NODAT (odds ratio [OR]=2.41, P=0.035) after correction for recipient age, weight, gender, ethnicity, and tacrolimus use. Age (OR=1.06), weight (OR=1.04), and nonwhite race (OR=5.04) were the other significant variables. We conclude that ADPKD is a significant risk factor for the development of NODAT. This may influence the follow up and management choices of these patients in the future.

Hypoadiponectinemia: A common basis for diseases associated with overnutrition

Adiponectin is a plasma protein derived from adipose tissue, which we discovered from a human adipose cDNA project. Adiponectin exists in circulating plasma at concentrations ranging from 4 to 30 microg/mL, which is much higher than the concentrations of various other hormones and cytokines. Adiponectin has a sticky nature, binding to collagen I, III, and V, which are present in vascular intima. Adiponectin exhibits various antiatherogenic effects on vascular cells, suppressing the expression of adhesion molecules in vascular endothelial cells, proliferation of smooth muscle cells, and cholesteryl-ester accumulation in macrophages. However, its plasma levels are low in subjects with excess intra-abdominal fat. Adiponectin also has antidiabetic properties, and plasma adiponectin levels correlate positively with insulin sensitivity. Several clinical studies have demonstrated that hypoadiponectinemia is a risk factor for new-onset diabetes. Recent studies suggest that hypoadiponectinemia may partly contribute to the development of salt-sensitive hypertension and hypertensive heart failure, and can be also a risk factor for overnutrition-related cancers such as breast, colon, uterine, and prostate cancers. Hypoadiponectinemia might be at least in part the molecular basis of various diseases associated with overnutrition.

New-onset diabetes after transplantation

For many years new-onset diabetes after transplantation has been recognized as a complication of solid-organ transplantation, although its importance has been greatly underestimated. Studies have shown that the cumulative incidence of this condition in heart transplant recipients may reach 32% at 5 years, similar to that reported in kidney and liver transplant patients. Several factors predispose to increased risk for developing new-onset diabetes after transplantation, including age, ethnicity, family history of diabetes, obesity and immunosuppressive therapy. Corticosteroids are associated with the greatest risk of developing the condition. Tacrolimus is more diabetogenic than cyclosporine in kidney and liver transplant patients, but there are few data reporting the effects of these agents in heart transplant patients. In kidney transplant patients, diabetes is known to be a significant risk factor for cardiovascular disease post-transplant. Although this has yet to be demonstrated clearly in heart transplant patients, evidence suggests that new-onset diabetes after transplantation may play a role in the development of cardiac allograft vasculopathy (CAV). Because CAV is the major limitation to long-term survival in this population, it is clear that efforts should be made to reduce the risk of diabetes and treat this condition appropriately. Management of transplant recipients with new-onset diabetes after transplantation has been assisted by the recent publication of International Consensus Guidelines. The guidelines were developed to establish a standard definition and describe risk factors for new-onset diabetes after transplantation. Use of these guidelines will help to prospectively identify those at risk of developing new-onset diabetes after transplantation so that therapeutic strategies can be individualized early in the treatment regimen. These management approaches should help to lower the risk of new-onset diabetes after heart transplantation and reduce the possible long-term consequences of the condition.