Biomedical subjects
Jøran Hjelmesaeth
Publications and source records attributed to Jøran Hjelmesaeth.
The natural course of cytomegalovirus infection and disease in renal transplant recipients.
A series of prospective studies of a large cohort population of renal transplant recipients who did not receive cytomegalovirus (CMV) prophylaxis or preemptive therapy examined the effects of CMV infection and disease on renal allograft rejection, long-term recipient and graft survival, and new-onset diabetes mellitus. CMV infection and disease were found to be independent risk factors for allograft rejection and new-onset diabetes mellitus within 100 days posttransplantation, and for recipient mortality and uncensored graft loss beyond 100 days posttransplantation. Additional studies are needed to determine whether CMV prophylaxis or preemptive therapy may be of benefit in preventing these complications.
Early posttransplant serum osteoprotegerin levels predict long-term (8-year) patient survival and cardiovascular death in renal transplant patients.
The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.
High mortality rates in conservatively managed patients with acute coronary syndrome.
OBJECTIVES: The revised diagnostic criteria for the acute coronary syndrome (ACS) have created the need for accurate and representative data on treatment and outcome for the three categories of ACS. DESIGN: Consecutive patients admitted with a suspected ACS (n = 755) from February 1, 2003 to January 31, 2004 was registered and categorised into five diagnostic groups: 1) ST-elevation myocardial infarction (STEMI) (n = 126), 2) Non-ST-elevation myocardial infarction (NSTEMI) (n = 185), 3) Unstable angina pectoris (UAP) (n = 55), 4) Coronary heart disease (CHD) without ACS (n = 164) and 5) Non-coronary chest pain (n = 225). RESULTS: All-cause one-year mortality rates were 20%, 32%, 7%, 10% and 3%, in patients with STEMI, NSTEMI, UAP, CHD without ACS and non-coronary chest pain, respectively. In patients with STEMI, 61% received immediate reperfusion therapy (ratio thrombolysis: primary PCI = 18:1). Only 3% of those with NSTEMI had PCI within two days. CONCLUSION: In this conservatively managed population of consecutive patients with ACS, the one-year mortality rate is significantly higher than seen in most registries and clinical trials.
Is there a link between cytomegalovirus infection and new-onset posttransplantation diabetes mellitus? Potential mechanisms of virus induced beta-cell damage.
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Short-term treatment with rosiglitazone improves glucose tolerance, insulin sensitivity and endothelial function in renal transplant recipients.
BACKGROUND: Insulin resistance (IR) contributes to the development of glucose intolerance (post-transplant diabetes mellitus or impaired glucose tolerance) following renal transplantation. Furthermore, endothelial dysfunction (ED) is associated with IR. Glucose intolerance, IR and ED are all independent risk factors for cardiovascular disease. Therefore, treatment with insulin sensitizers may benefit glucose-intolerant renal transplant recipients. The main objectives of the present study were to investigate the effect of 4 weeks' treatment with the PPAR-gamma agonist rosiglitazone on insulin sensitivity, plasma glucose and endothelial function in renal transplant recipients with glucose intolerance. Safety parameters were also addressed. METHODS: A total of 10 glucose-intolerant renal transplant recipients were treated with rosiglitazone (initially 4 mg/day increasing to 8 mg/day after 1 week). A hyperinsulinaemic euglycaemic glucose clamp, an oral glucose tolerance test and endothelial function assessment with laser Doppler flowmetry were performed both at baseline and at follow-up. RESULTS: Treatment with rosiglitazone was followed by a significantly improved mean glucose disposal rate (from 6.5 to 9.1 g/kg/min; P = 0.02) and a significant decline in fasting and 2 h plasma glucose (from 6.4 to 5.8 mmol/l, P = 0.01 and from 14.2 to 10.6 mmol/l, P = 0.03, respectively). Furthermore, a significant improvement in endothelial function was demonstrated (AUC(ACh); from 389 to 832 AU x min, P = 0.04). No serious adverse events or hypoglycaemic episodes were observed. CONCLUSIONS: Four weeks' treatment with rosiglitazone was associated with increased insulin sensitivity, lowered fasting and 2 h plasma glucose and improved endothelial function in renal transplant recipients with glucose intolerance. The drug was well tolerated and may be a good alternative for treating these patients.
[Prehospital diagnosis and treatment of acute myocardial infarction in Vestfold].
BACKGROUND: Pre-hospital thrombolysis is a relatively new treatment modality in Norway. The present study is a county-based evaluation of the first phase of this procedure after its introduction in 2002. MATERIALS AND METHODS: This is a retrospective cohort study of all patients who, over a nine-month period, had a pre-hospital ECG taken by paramedics and transmitted to the county's two coronary care units. The medical records of all patients who received pre-hospital thrombolysis were analysed and compared with those who received in-hospital thrombolysis over the same period. MATERIAL AND METHODS: A pre-hospital ECG was successfully taken and transmitted in 840 patients. Pre-hospital thrombolytic therapy was given to 45 (5.4%) patients, of whom 38 (84%) developed ST-elevation myocardial infarction (STEMI). Over the same period, 32 patients received in-hospital thrombolysis, of whom 28 (87%) developed STEMI. Among the 738 hospitalised patients who did not receive pre-hospital thrombolytic therapy, 218 (28%) had a diagnosis of acute coronary syndrome, 258 (35%) had established coronary heart disease but no evidence of coronary ischaemia, while 262 (36%) had no evidence of coronary heart disease at all. Median call-to-thrombolysis time was 42 minutes (range 21-75). INTERPRETATION: The findings indicate good paramedical pre-hospital routines with short call-to-thrombolysis-time, but the routines for pre-hospital ECG and thrombolytic therapy need reassessment.
Insulin resistance after renal transplantation: the effect of steroid dose reduction and withdrawal.
Cardiovascular disease is a prevalent and serious complication after solid organ transplantation. Treatment with glucocorticoids is associated with increased risk for diabetes mellitus, insulin resistance, weight gain, hypercholesterolemia, and hypertension, all shown to be independent risk factors for cardiovascular disease. We sought to test the hypothesis that tapering of prednisolone (TAP) the first year after renal transplantation improves insulin sensitivity (IS), and to assess the effect of complete steroid withdrawal (SW) on IS in patients on a cyclosporine-based immunosuppressive regimen. All patients (n = 57) completed two consecutive hyperinsulinemic euglycemic glucose clamp procedures, a TAP group (n = 34) and a control group (n = 12) at 3 and 12 mo after transplantation, and a SW group (n = 11) before and 5 mo after SW. The IS index (ISI) was calculated as the glucose disposal rate divided by mean serum insulin the last 60 min of the clamp. In the TAP group, the mean (range) daily prednisolone was reduced from 16 (10 to 30) to 9 (5 to 12.5) mg accompanied by an average increased ISI of 24% (P = 0.008). In contrast, no significant change in ISI was observed in the control group (0%, P = 0.988). In the SW group, withdrawal of 5 mg prednisolone did not influence mean ISI significantly (-8%, P = 0.206). Lowering daily prednisolone toward 5 mg/d has beneficial effects on insulin action after renal transplantation, but withdrawal of 5 mg prednisolone may not influence IS significantly.
[Percutaneous coronary intervention].
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Determinants of insulin secretion after renal transplantation.
The high prevalence of post-transplant glucose intolerance and insulin resistance (IR) is associated with older age, family history of diabetes, immunosuppressive drugs, and antihypertensive therapy. However, the potential determinants of post-transplant beta-cell dysfunction are largely unknown. The objective of the present study was to address this issue in detail. A total of 167 previously nondiabetic renal transplant recipients underwent a 75-g oral glucose tolerance test (OGTT)10 weeks after transplantation. Serum glucose and insulin were measured at 0, 1, and 2 hours. Three insulin release indices (Secr(AUC), Secr(1.phase), and Secr(2.phase)) were calculated to assess the insulin secretory response as the dependent variable. To account for variations in insulin sensitivity (IS), beta-cell function was also estimated as the disposition index (DI); the product of the IS index (ISI(TX)) and Secr(1.phase). Increasing age was strongly and independently associated with a blunted insulin secretory response even after adjustment for IS (P =.001). An 80-year-old recipient had an approximately 50% lower insulin release than a 20-year-old individual, based on the linear regression model. Cytomegalovirus (CMV) disease and treatment with furosemide were both independently associated with beta-cell dysfunction (DI; P <.001 and P =.008). Patients treated with angiotensin-converting enzyme (ACE)-inhibitors had an enhanced absolute insulin release, but the DI was similar in both treated and untreated recipients. We conclude that older age is an important determinant of beta-cell dysfunction after renal transplantation. CMV disease and treatment with furosemide may also negatively influence pancreatic insulin release in renal transplant recipients.
Losartan for cardiovascular disease in patient's with and without diabetes in the LIFE study.
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The impact of impaired insulin release and insulin resistance on glucose intolerance after renal transplantation.
The current knowledge of the pathogenesis of post-transplant glucose intolerance is sparse. This study was undertaken to assess the relative importance of insulin secretion (ISec) and insulin sensitivity (IS) in the pathogenesis of post-transplant diabetes mellitus (PTDM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) after renal transplantation. An oral glucose tolerance test (OGTT) was performed in 167 non-diabetic recipients 10 wk after renal transplantation. Fasting, 1-h and 2-h insulin and glucose levels were used to estimate the insulin secretory response and IS. One year after transplantation 89 patients were re-examined with an OGTT including measurements of fasting and 2 h glucose. Ten weeks after transplantation the PTDM-patients had significantly lower ISec and IS than patients with IGT/IFG, who again had lower ISec and IS than those with normal glucose tolerance (NGT). One year later, a similar difference in baseline ISec was observed between the three groups, whereas baseline IS did not differ significantly. Patients who improved their glucose tolerance during the first year, were mainly characterized by a significantly greater baseline ISec, and they received a significantly higher median prednisolone dose at baseline with a subsequent larger dose reduction during the first year, than the patients who had their glucose tolerance unchanged or worsened. In conclusion, both impaired ISec and IS characterize patients with PTDM and IGT/IFG in the early course after renal transplantation. The presence of defects in insulin release, rather than insulin action, indicates a poor prognosis regarding later normalization of glucose tolerance.
Response to Montori et al. Post-transplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management of the disease.
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Association between insulin resistance and endothelial dysfunction in renal transplant recipients.
BACKGROUND: Endothelial dysfunction is a common finding in renal transplant recipients (RTR) and is related to impaired local regulation of vasodilative and vasoconstrictive substances, such as nitric monoxide (NO) and endothelin-1 (ET-1). In non-transplanted patients, an association between impaired endothelial function and insulin resistance has been shown. Whether such an association also exists in RTR is unknown. OBJECTIVE: The aim of the present study was to examine whether insulin resistance is associated with endothelial dysfunction in RTR. MATERIAL AND METHODS: A total of 47 RTR in a stable phase six yr post-transplant were included in the statistical analysis. The immunosuppressive therapy was based on cyclosporine and prednisolone. Non-invasive assessment of endothelial function was performed with laser Doppler flowmetry of the forearm skin vasculature after local acetylcholine stimulation. Oral glucose tolerance tests comprising both glucose and insulin measurements were used to calculate insulin sensitivity (IS) indices. NO, ET-1 and von Willebrand factor were measured in fasting plasma samples. RESULTS: Normal glucose tolerance was found in 31 RTR. In these subjects, both IS (r(2) = 0.164, p = 0.044) and plasma NO (r(2) = 0.326, p = 0.002) were significantly correlated with endothelial function. Patients with glucose intolerance (n = 16) had higher plasma ET-1 and lower NO levels, but the association between IS and endothelial function was not significant in these subjects. In the total patient cohort, IS and endothelial function tended to be correlated (p = 0.127). CONCLUSIONS: Endothelial dysfunction is significantly associated with insulin resistance in normoglycemic RTR but explains a rather small part of the variation. In glucose-intolerant recipients, IS appears to be more critically dependent on other factors not revealed in the present study.