Trond Jenssen | University of Tromsø (original) (raw)

Papers by Trond Jenssen

Research paper thumbnail of Visceral fat is better related to impaired glucose metabolism than body mass index after kidney transplantation

Transplant International, 2015

The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We eval... more The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post-transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P < 0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An association between BMI and 2-h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R(2) = 0.132, P < 0.001 and R(2) = 0.097, P = 0.001, respectively for fasting and 2-h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM.

Research paper thumbnail of Emerging treatments for post-transplantation diabetes mellitus

Nature Reviews Nephrology, 2015

| Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM)... more | Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM), occurs in 10-15% of renal transplant recipients and is associated with cardiovascular disease and reduced lifespan. In the majority of cases, PTDM is characterized by β-cell dysfunction, as well as reduced insulin sensitivity in liver, muscle and adipose tissue. Glucose-lowering therapy must be compatible with immunosuppressant agents, reduced glomerular filtration rate (GFR) and severe arteriosclerosis. Such therapy should not place the patient at risk by inducing hypoglycaemic episodes or exacerbating renal function owing to adverse gastrointestinal effects with hypovolaemia. First-generation and secondgeneration sulphonylureas are generally avoided, and caution is currently advocated for the use of metformin in patients with GFR <60 ml/min/1.73 m 2 . DPP-4 inhibitors do not interact with immunosuppressant drugs and have demonstrated safety in small clinical trials. Other therapeutic options include glinides and glitazones. Evidence-based treatment regimens used in patients with type 2 diabetes mellitus cannot be directly implemented in patients with PTDM. Studies investigating the latest drugs are required to direct the development of improved treatment strategies for patients with PTDM. This Review outlines the modern principles of glucose-lowering treatment in PTDM with specific reference to renal transplant recipients.

Research paper thumbnail of The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

Clinical journal of the American Society of Nephrology : CJASN, Jan 10, 2015

Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fat... more Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with l...

Research paper thumbnail of Graft function 1 year after pregnancy in an islet-transplanted patient

Transplant International, 2015

Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), b... more Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), but pregnancy has generally not been advised for women after receiving an islet allograft. We hereby describe what is to our knowledge the first successful pregnancy and persistent graft function in a woman 4 years after her initial islet transplantation. A 37-year-old woman with brittle type 1 diabetes was transplanted with two separate islet graft infusions, eventually becoming insulin independent. Ten months after her second transplantation, her immunosuppression was switched from tacrolimus and sirolimus to tacrolimus, azathioprine, and prednisolone, due to her wish to become pregnant. She became pregnant one year later, and after 38 weeks of uncomplicated pregnancy, she gave birth to a healthy child by C-section. The current report suggests that pregnancy and childbirth can be accomplished after islet transplantation without loss of islet graft function.

Research paper thumbnail of Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients

Clinical pharmacology and therapeutics, 2009

The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obe... more The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obese patients being treated with 20-80 mg atorvastatin each morning. Eight-hour pharmacokinetic investigations were performed the day before the surgery and at a median of 5 weeks (range 3-6 weeks) after the surgery. Gastric bypass surgery produced a variable effect on individual systemic exposure to atorvastatin acid (area under the plasma concentration vs. time curve from 0 to 8 h postdose (AUC(0-8))), ranging from a threefold decrease to a twofold increase (median ratio = 1.1, P = 0.99). Patients with the highest systemic exposure to atorvastatin before surgery showed reduced exposure after surgery (n = 3, median ratio = 0.4, range = 0.3-0.5, P < 0.01), whereas those with lower systemic exposure before surgery showed a median 1.2-fold increase in atorvastatin AUC(0-8) (n = 9, range = 0.8-2.3, P = 0.03) after surgery. This study indicates that the presurgical first-pass metabolic capa...

Research paper thumbnail of Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch

Clinical pharmacology and therapeutics, 2010

Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgic... more Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure. Given that this procedure introduces a bypass of the proximal small intestine, it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability. Eight-hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at (median) 6 weeks (range, 4-8 weeks) in 10 morbidly obese patients who were receiving treatment with 20-80 mg atorvastatin each morning. The bioavailability of atorvastatin acid was significantly increased, with a mean twofold higher AUC(0-8) after surgery (range 1.0-4.2, P = 0.001). Time to maximum plasma concentration (C(max)) increased from 1.2 h before surgery to 2.3 h after surgery (P = 0.03). The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds. Consequently, retitration to the lowest effective dose should be considere...

Research paper thumbnail of Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy

Nephron, 2000

We present a 50-year-old female who experienced generalized convulsion 3 months after a successfu... more We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rif...

Research paper thumbnail of Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

Transplantation Research, 2012

Background: Acute rejection (AR) episodes in renal transplant recipients are suspected when plasm... more Background: Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Noninvasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population.

Research paper thumbnail of Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Diabetes Research and Clinical Practice, 2015

Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (... more Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9-12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys. Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass-spectrometry. The SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40 mmol/mol) and 8.6% (70 mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients. Patients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.

Research paper thumbnail of Early Posttransplantation Hyperglycemia in Kidney Transplant Recipients Is Associated With Overall Long-term Graft Losses

Transplantation Journal, 2012

The association of early-onset posttransplantation hyperglycemia with long-term renal allograft s... more The association of early-onset posttransplantation hyperglycemia with long-term renal allograft survival is unknown. Seventy-one (SD 9) days after transplantation, 1410 first-time kidney transplant recipients without diabetes underwent an oral glucose tolerance test and were observed until primary outcome (graft loss) or December 31, 2008 (median [range], 6.0 years [0.3-13.8 years]). We used multivariable Cox regression analysis adjusted for age, gender, body mass index, creatinine level, donor age, preemptive transplantation, deceased donor, early rejection, and early cytomegalovirus infection to estimate hazard ratios for overall and death-censored allograft survival. A total of 392 (28%) recipients experienced graft failure, and 235 (60%) were induced by death. Each 1 mmol/L increase in 2-hr plasma glucose (2hPG) was associated with 7% and 3% increased risk of unadjusted and adjusted overall graft failure (hazard ratio [95% confidence interval], 1.07 [1.04-1.10] and 1.03 [1.00-1.07]). Fasting plasma glucose was associated with unadjusted but not adjusted overall graft failure (1.09 [1.01-1.18] and 1.07 [0.98-1.17]). Neither 2hPG nor fasting plasma glucose was associated with death-censored graft loss (P=0.578 and P=0.896). Compared with recipients with normal glucose tolerance, recipients with posttransplantation diabetes mellitus showed a tendency toward increased overall multiadjusted graft failure (1.30 [0.98-1.73]). This was not observed in patients with impaired fasting glucose or impaired glucose tolerance. In this study, 2hPG was associated with overall graft failure but not death-censored graft failure. The link between 2hPG and graft failure may be explained by the association with mortality.

Research paper thumbnail of Reduced Incidence of New-Onset Posttransplantation Diabetes Mellitus During the Last Decade

Transplantation, 2007

A previous study (1995-1996) of 173 nondiabetic renal transplant recipients (historical cohort; H... more A previous study (1995-1996) of 173 nondiabetic renal transplant recipients (historical cohort; HC) revealed a 20% incidence of new-onset posttransplantation diabetes mellitus (PTDM) and 32% with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). We examined whether glucose tolerance has improved after recent changes in our immunosuppressive protocol and a switch from deferred to preemptive cytomegalovirus (CMV) therapy. A total of 321 consecutive, nondiabetic patients (new cohort; NC) were examined 10 weeks after kidney transplantation with an oral glucose tolerance test (n=301) between January 2004 and December 2005. Although recipients in the NC were on average 3 years older [mean (SD): 50.3 (14.6) vs. 47.4 (16.0), P=0.038] and had a higher mean body mass index [24.5 (3.6) vs. 23.5 (3.8) kg/m(2), P=0.003], a significantly lower incidence of both PTDM (13%) and IGT/IFG (18%) was observed in the NC (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) as compared to the HC. The patients in the NC received a significantly lower mean daily oral prednisolone dose [13.2 (4.7) vs. 15.3 (6.6) mg/day, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001], and had lower frequencies of rejections (36% vs. 57%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and CMV infection (54% vs. 63%, P=0.071). Patients in the NC had significantly lower odds of developing PTDM, even after adjustment for age, prednisolone dose, HLA-B27 status and CMV infection (odds ratio: 0.42, 95% CI: 0.23-0.77, P=0.005). The odds of developing PTDM are more than halved over the last decade. Possible explanations are changes in immunosuppressive therapy, fewer rejections, and lower doses of steroids.

Research paper thumbnail of Fasting Plasma Glucose and Glycosylated Hemoglobin in the Screening for Diabetes Mellitus After Renal Transplantation

Transplantation, 2009

Fasting plasma glucose (fPG) is recommended to identify new-onset posttransplant diabetes mellitu... more Fasting plasma glucose (fPG) is recommended to identify new-onset posttransplant diabetes mellitus (PTDM), but an oral glucose tolerance test (OGTT) has higher diagnostic sensitivity. We aimed to assess the accuracy of fPG and glycosylated hemoglobin (HbA1c) for the selection of patients who should undergo a diagnostic OGTT 10 weeks after renal transplantation. A total of 1571 renal transplant recipients without prior diabetes underwent an OGTT 10 weeks after transplantation. Receiver operating characteristic analyses were used to identify optimal thresholds to incite further diagnostic tests. A sensitivity level of 80% was chosen for screening purpose. We diagnosed PTDM in 213 (14%) patients of whom 109 (51%) were identified by 2-hr plasma glucose more than or equal to 11.1 mmol/L alone, 35 (17%) by fPG alone, and 69 (32%) by both criteria. Receiver operating characteristic analysis revealed an area under the curve of 0.761 (95% confidence interval 0.714-0.809) for fPG and 0.817 (95% confidence interval 0.758-0.876) for HbA1c. Performing an OGTT on patients with an fPG more than or equal to 5.3 mmol/L or HbA1c more than or equal to 5.8% predicted diabetes with 81% and 83% sensitivity, requiring 49% and 41% of the patients to be tested, respectively. The combined criterion fPG more than or equal to 5.0 mmol/L and HbA1c more than or equal to 5.7%, provided a similar sensitivity (79%) from testing only 29% of the population. We conclude that patients with an fPG between 5.3 and 6.9 mmol/L or HbA1c more than or equal to 5.8%, alternatively an fPG more than or equal to 5.0 mmol/L combined with HbA1c more than or equal to 5.7% in the early posttransplant period should undergo an OGTT for diagnostic verification of PTDM.

Research paper thumbnail of Determinants of short-term changes in body composition following renal transplantation

Scandinavian Journal of Urology and Nephrology, 2009

Changes in body composition after renal transplantation (RTx) are of clinical significance, since... more Changes in body composition after renal transplantation (RTx) are of clinical significance, since increments in fat mass may contribute to glucose intolerance and cardiovascular morbidity. The aim of this study was to quantify the early changes in body composition after transplantation and identify predictors of these changes. Total and regional body composition of 102 first kidney allograft recipients were measured at transplantation and after 10 weeks using dual-energy X-ray absorptiometry. The population comprised a high proportion of pre-emptive and well-nourished kidney recipients. Multiple linear regression was used to identify predictors of change. Mean fat mass was 27.1+/-8.7% of body weight at baseline. The fat mass percentage increased by 2.2% corresponding to a 1.3 kg increase in fat mass at 10 weeks (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Fat-free mass declined by 2.5 kg (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), with no significant loss of body weight (0.9 kg, p=0.11). Age, low-tertile fat mass, plasma C-reactive protein, time on dialysis and cumulative prednisolone dose were independent predictors (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) of the increase in fat mass. Cumulative prednisolone dose was the only significant predictor of decrease in fat-free mass. Essentially the same results were found for both genders. A significant increase in fat mass occurred rapidly after RTx along with a reduction in fat-free mass despite stable body weight. Early fat mass accumulation may predispose to comorbidity, but the long-term clinical significance of these early changes remains to be explored in prospective studies.

Research paper thumbnail of Fasting Plasma Glucose in the Screening for Type 2 Diabetes in Morbidly Obese Subjects

Obesity Surgery, 2010

Background Higher mortality rates among morbidly obese (BMI of ≥40 or ≥35 kg/m 2 with weight-rela... more Background Higher mortality rates among morbidly obese (BMI of ≥40 or ≥35 kg/m 2 with weight-related comorbidities) subjects are mainly explained by comorbidities such as type 2 diabetes. As bariatric surgery ameliorates diabetes, obese diabetic subjects will receive great benefits from bariatric surgery. Screening for diabetes prior to surgical referral is therefore crucial. Methods We studied 1,253 consecutively recruited (2005)(2006)(2007)(2008) morbidly obese subjects (67% women). Among subjects without known diabetes, 70% (670/961) performed an oral glucose tolerance test (OGTT). Screen-detected diabetes was defined as fasting plasma glucose (fPG) ≥7.0 mmol/l and/or 2-h glucose concentration (2hPG) ≥ 11.1 mmol/l. Results Within the study population, 31% had diabetes, of which 8% were screen-detected. Eighty percent of those with screen-detected diabetes were diagnosed by fPG. In subjects with nondiabetic fPG concentrations, elevating the fPG cutoff value from 5.2 mmol/l to the World Health Organization's (WHO's) recommended value of 6.1 mmol/l reduced the percentage of the population needing an OGTT considerably (78-23%), but only slightly reduced the sensitivity of fPG in detecting a diabetic 2hPG concentration (100-77%). Only 7% of the patients with fPG between 6.1 and 6.9 mmol/l had a diabetic 2hPG concentration. Following the WHO's recommendations, we found that 95% of all subjects with unknown diabetes were identified. Conclusions Fasting glucose identified four out of five morbidly obese subjects with unknown diabetes. A supplemental OGTT in selected persons identified the majority of the remaining diabetic cases.

Research paper thumbnail of A 6-year prospective study on new onset diabetes mellitus, insulin release and insulin sensitivity in renal transplant recipients

Background. It is well known that both insulin resistance and insulin deficiency are involved in ... more Background. It is well known that both insulin resistance and insulin deficiency are involved in the pathogenesis of post-transplant diabetes mellitus (PTDM), but the relative importance of the two different mechanisms is still under debate. The present prospective longitudinal study was performed over 6 years to investigate the impact of impaired insulin secretion (ISec) and insulin sensitivity (IS) in the

Research paper thumbnail of Impaired glucose homeostasis in renal transplant recipients receiving basiliximab

Nephrology Dialysis Transplantation, 2010

Background. The pathogenesis of new onset diabetes after transplantation (NODAT) is multifactoria... more Background. The pathogenesis of new onset diabetes after transplantation (NODAT) is multifactorial. Suppression of regulatory T lymphocytes may have a negative impact on pancreatic β-cells. Induction with basiliximab affects reg-ulatory T-cell function and may therefore, theoretically, also affect glucose homeostasis in renal transplant recipients. Methods. All kidney recipients ≥50 years of age without diabetes mellitus transplanted from 1 January 2005 to 31 December 2007 were included in a single-centre retrospec-Impaired glucose homeostasis in renal transplant recipients receiving basiliximab 1289 by guest on March 11, 2016 http://ndt.oxfordjournals.org/ Downloaded from (IFG) versus 36.9% in the group without induction therapy (P = 0.017). In recipients with normal OGTT, the mean fasting glucose at 10 weeks was 5.18 mmol/l (SD: 0.54) in the basiliximab group (n = 65) and 4.84 mmol/l (SD: 0.64) in the no induction group (n = 82) (P = 0.001).

Research paper thumbnail of Glucose tolerance before and after renal transplantation

Nephrology Dialysis Transplantation, 2010

Renal insufficiency predisposes to insulin resistance, hyperparathyroidism and derangements in ca... more Renal insufficiency predisposes to insulin resistance, hyperparathyroidism and derangements in calcium phosphate and nitrogenous compound balance, leading to pre-transplant hyperglycaemia. These metabolic risk factors are not fully corrected after renal transplantation. The present study aimed to assess the role of pre-transplant glycaemia and the named metabolic risk factors in post-transplant hyperglycaemia [PHYG; impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes mellitus (DM)]. This is a retrospective cohort study involving 301 patients without pre-transplant DM. Measurements included a pre- and post-transplant oral glucose tolerance test (OGTT) as well as glomerular filtration rate (GFR), parathyroid hormone (PTH), phosphate, calcium and urea measured 10 weeks post-transplant. The risk of PHYG at 10 weeks post-transplant was analysed using multiple logistic regression. Ninety-three patients (31%) had PHYG (two IFG, 52 IGT, 39 DM). Variables associated with PHYG included pre-transplant 2-h glycaemia [OR 1.26, 95% CI (1.09, 1.46)] and post-transplant urea levels [OR 1.14, 95% CI (1.02, 1.27)]. Older age, non-Caucasian ethnicity, previous transplants, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=3 HLA class 1 mismatches and high prednisolone doses were likewise associated with an increased PHYG risk (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Pre-transplant glycaemia and high post-transplant levels of urea were associated with a greater risk of PHYG. This seemed to be independent of GFR, PTH, phosphate, calcium and traditional risk factors such as age and glucocorticoid load.

Research paper thumbnail of Short-term treatment with rosiglitazone improves glucose tolerance, insulin sensitivity and endothelial function in renal transplant recipients

Nephrology Dialysis Transplantation, 2005

Background. Insulin resistance (IR) contributes to the development of glucose intolerance (post-t... more 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-g 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 ¼ 0.02) and a significant decline in fasting and 2 h plasma glucose (from 6.4 to 5.8 mmol/l, P ¼ 0.01 and from 14.2 to 10.6 mmol/l, P ¼ 0.03, respectively). Furthermore, a significant improvement in endothelial function was demonstrated (AUC ACh ; from 389 to 832 AU Á min, P ¼ 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.

Research paper thumbnail of The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensitivity in man

Nephrology Dialysis Transplantation, 2007

Background. The objectives of the present study were to investigate the possible adverse effects ... more Background. The objectives of the present study were to investigate the possible adverse effects of ciclosporin A (CsA, Sandimmun Neoral Õ ) on insulin secretion and insulin sensitivity (IS) in man. Methods. A total of 11 Caucasian non-diabetic haemodialysis (HD) patients were recruited from the Norwegian transplant waiting list to participate in this study. The patients underwent two consecutive 3 h hyperglycaemic glucose clamp procedures, before and following 2 weeks of oral CsA treatment. Statistical analyses included nine patients (7M/2F, mean age 61 AE 14 years) as two patients were withdrawn due to side effects and poor compliance. First and second phase insulin secretion (Secr 1.phase and Secr 2.phase ) were estimated as area under the insulin serum concentration vs time curve (AUC) during the first 10 min and the last hour of the clamp, respectively. The IS index (ISI) was calculated as the glucose disposal rate corrected for insulin levels during the last 60 min of the procedure. Results. Secr 2.phase decreased significantly (30%) following CsA treatment (P ¼ 0.045). In contrast, no significant change was observed in the average Secr 1.phase or ISI, although relatively large interindividual differences were present. Calculation based on C-peptide concentrations gave the same results. No significant changes in body weight, dialysis status, patient medication or safety parameters were observed. Conclusions. Short-term treatment with CsA at doses used following transplantation seems to impair Secr 2.phase , but has no significant effect on Secr 1.phase , in Caucasian HD patients. The mechanism behind these findings and their possible clinical implications need further study.

Research paper thumbnail of Determinants of insulin secretion after renal transplantation

Metabolism, 2003

The high prevalence of post-transplant glucose intolerance and insulin resistance (IR) is associa... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.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.

Research paper thumbnail of Visceral fat is better related to impaired glucose metabolism than body mass index after kidney transplantation

Transplant International, 2015

The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We eval... more The role of visceral adipose tissue (VAT) in post-transplant hyperglycaemia is not known. We evaluated 167 patients without diabetes 8-10 weeks after kidney transplantation, performing oral glucose tolerance tests and measuring VAT content from dual-energy X-ray absorptiometry scans. Median VAT weight in normal glucose tolerance patients was 0.9 kg, impaired fasting glucose patients 1.0 kg, impaired glucose tolerance patients 1.3 kg and patients with post-transplant diabetes (PTDM) 2.1 kg (P = 0.004, indicating a difference between groups). Percentage VAT of total body fat was associated with fasting (R(2) = 0.094, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and 2-h glucose concentration (R(2) = 0.062, P = 0.001), while BMI was only associated with 2-h glucose concentration (R(2) = 0.029, P = 0.028). An association between BMI and 2-h glucose concentration was lost in adjusted models, as opposed to the associations between VAT as percentage of total body fat and glucose concentrations (R(2) = 0.132, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 and R(2) = 0.097, P = 0.001, respectively for fasting and 2-h glucose concentration). In conclusion, VAT is more closely related to impaired glucose metabolism than BMI after kidney transplantation. The association with central obesity should encourage additional studies on lifestyle interventions to prevent PTDM.

Research paper thumbnail of Emerging treatments for post-transplantation diabetes mellitus

Nature Reviews Nephrology, 2015

| Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM)... more | Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM), occurs in 10-15% of renal transplant recipients and is associated with cardiovascular disease and reduced lifespan. In the majority of cases, PTDM is characterized by β-cell dysfunction, as well as reduced insulin sensitivity in liver, muscle and adipose tissue. Glucose-lowering therapy must be compatible with immunosuppressant agents, reduced glomerular filtration rate (GFR) and severe arteriosclerosis. Such therapy should not place the patient at risk by inducing hypoglycaemic episodes or exacerbating renal function owing to adverse gastrointestinal effects with hypovolaemia. First-generation and secondgeneration sulphonylureas are generally avoided, and caution is currently advocated for the use of metformin in patients with GFR <60 ml/min/1.73 m 2 . DPP-4 inhibitors do not interact with immunosuppressant drugs and have demonstrated safety in small clinical trials. Other therapeutic options include glinides and glitazones. Evidence-based treatment regimens used in patients with type 2 diabetes mellitus cannot be directly implemented in patients with PTDM. Studies investigating the latest drugs are required to direct the development of improved treatment strategies for patients with PTDM. This Review outlines the modern principles of glucose-lowering treatment in PTDM with specific reference to renal transplant recipients.

Research paper thumbnail of The Association between Marine n-3 Polyunsaturated Fatty Acid Levels and Survival after Renal Transplantation

Clinical journal of the American Society of Nephrology : CJASN, Jan 10, 2015

Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fat... more Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants. In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation. There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels (≥7.95 weight percentage) compared with l...

Research paper thumbnail of Graft function 1 year after pregnancy in an islet-transplanted patient

Transplant International, 2015

Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), b... more Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), but pregnancy has generally not been advised for women after receiving an islet allograft. We hereby describe what is to our knowledge the first successful pregnancy and persistent graft function in a woman 4 years after her initial islet transplantation. A 37-year-old woman with brittle type 1 diabetes was transplanted with two separate islet graft infusions, eventually becoming insulin independent. Ten months after her second transplantation, her immunosuppression was switched from tacrolimus and sirolimus to tacrolimus, azathioprine, and prednisolone, due to her wish to become pregnant. She became pregnant one year later, and after 38 weeks of uncomplicated pregnancy, she gave birth to a healthy child by C-section. The current report suggests that pregnancy and childbirth can be accomplished after islet transplantation without loss of islet graft function.

Research paper thumbnail of Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients

Clinical pharmacology and therapeutics, 2009

The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obe... more The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obese patients being treated with 20-80 mg atorvastatin each morning. Eight-hour pharmacokinetic investigations were performed the day before the surgery and at a median of 5 weeks (range 3-6 weeks) after the surgery. Gastric bypass surgery produced a variable effect on individual systemic exposure to atorvastatin acid (area under the plasma concentration vs. time curve from 0 to 8 h postdose (AUC(0-8))), ranging from a threefold decrease to a twofold increase (median ratio = 1.1, P = 0.99). Patients with the highest systemic exposure to atorvastatin before surgery showed reduced exposure after surgery (n = 3, median ratio = 0.4, range = 0.3-0.5, P < 0.01), whereas those with lower systemic exposure before surgery showed a median 1.2-fold increase in atorvastatin AUC(0-8) (n = 9, range = 0.8-2.3, P = 0.03) after surgery. This study indicates that the presurgical first-pass metabolic capa...

Research paper thumbnail of Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch

Clinical pharmacology and therapeutics, 2010

Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgic... more Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure. Given that this procedure introduces a bypass of the proximal small intestine, it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability. Eight-hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at (median) 6 weeks (range, 4-8 weeks) in 10 morbidly obese patients who were receiving treatment with 20-80 mg atorvastatin each morning. The bioavailability of atorvastatin acid was significantly increased, with a mean twofold higher AUC(0-8) after surgery (range 1.0-4.2, P = 0.001). Time to maximum plasma concentration (C(max)) increased from 1.2 h before surgery to 2.3 h after surgery (P = 0.03). The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds. Consequently, retitration to the lowest effective dose should be considere...

Research paper thumbnail of Intracerebral abscess caused by Nocardia otitidiscaviarum in a renal transplant patient--cured by evacuation plus antibiotic therapy

Nephron, 2000

We present a 50-year-old female who experienced generalized convulsion 3 months after a successfu... more We present a 50-year-old female who experienced generalized convulsion 3 months after a successful cadaveric renal transplantation. The first cerebral CT scan indicated cerebral frontal infarction. Repeat CT some days later revealed progressive lesions, and a highly malignant tumor or abscess was suspected. Antifungal and broad-spectrum antibacterial therapy was initiated. Cerebral MRI could not differentiate between these conditions, but a neutrophil granulocyte scan strongly suggested an infectious process. A stereotactic puncture of the frontal lobe was followed by temporary improvement. A severe progressive left-sided hemiparalysis gave indication for a craniotomy with evacuation of the abscess 9 days later. Culture of aspirated pus yielded growth of a gram-positive, rod-shaped bacterium, later identified as Nocardia otitidiscaviarum by sequencing the 16S rRNA. The patient was treated with meropenem plus rifampicin intravenously for 6 weeks followed by oral ciprofloxacin and rif...

Research paper thumbnail of Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

Transplantation Research, 2012

Background: Acute rejection (AR) episodes in renal transplant recipients are suspected when plasm... more Background: Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Noninvasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population.

Research paper thumbnail of Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Diabetes Research and Clinical Practice, 2015

Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (... more Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9-12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys. Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass-spectrometry. The SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40 mmol/mol) and 8.6% (70 mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients. Patients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.

Research paper thumbnail of Early Posttransplantation Hyperglycemia in Kidney Transplant Recipients Is Associated With Overall Long-term Graft Losses

Transplantation Journal, 2012

The association of early-onset posttransplantation hyperglycemia with long-term renal allograft s... more The association of early-onset posttransplantation hyperglycemia with long-term renal allograft survival is unknown. Seventy-one (SD 9) days after transplantation, 1410 first-time kidney transplant recipients without diabetes underwent an oral glucose tolerance test and were observed until primary outcome (graft loss) or December 31, 2008 (median [range], 6.0 years [0.3-13.8 years]). We used multivariable Cox regression analysis adjusted for age, gender, body mass index, creatinine level, donor age, preemptive transplantation, deceased donor, early rejection, and early cytomegalovirus infection to estimate hazard ratios for overall and death-censored allograft survival. A total of 392 (28%) recipients experienced graft failure, and 235 (60%) were induced by death. Each 1 mmol/L increase in 2-hr plasma glucose (2hPG) was associated with 7% and 3% increased risk of unadjusted and adjusted overall graft failure (hazard ratio [95% confidence interval], 1.07 [1.04-1.10] and 1.03 [1.00-1.07]). Fasting plasma glucose was associated with unadjusted but not adjusted overall graft failure (1.09 [1.01-1.18] and 1.07 [0.98-1.17]). Neither 2hPG nor fasting plasma glucose was associated with death-censored graft loss (P=0.578 and P=0.896). Compared with recipients with normal glucose tolerance, recipients with posttransplantation diabetes mellitus showed a tendency toward increased overall multiadjusted graft failure (1.30 [0.98-1.73]). This was not observed in patients with impaired fasting glucose or impaired glucose tolerance. In this study, 2hPG was associated with overall graft failure but not death-censored graft failure. The link between 2hPG and graft failure may be explained by the association with mortality.

Research paper thumbnail of Reduced Incidence of New-Onset Posttransplantation Diabetes Mellitus During the Last Decade

Transplantation, 2007

A previous study (1995-1996) of 173 nondiabetic renal transplant recipients (historical cohort; H... more A previous study (1995-1996) of 173 nondiabetic renal transplant recipients (historical cohort; HC) revealed a 20% incidence of new-onset posttransplantation diabetes mellitus (PTDM) and 32% with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). We examined whether glucose tolerance has improved after recent changes in our immunosuppressive protocol and a switch from deferred to preemptive cytomegalovirus (CMV) therapy. A total of 321 consecutive, nondiabetic patients (new cohort; NC) were examined 10 weeks after kidney transplantation with an oral glucose tolerance test (n=301) between January 2004 and December 2005. Although recipients in the NC were on average 3 years older [mean (SD): 50.3 (14.6) vs. 47.4 (16.0), P=0.038] and had a higher mean body mass index [24.5 (3.6) vs. 23.5 (3.8) kg/m(2), P=0.003], a significantly lower incidence of both PTDM (13%) and IGT/IFG (18%) was observed in the NC (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) as compared to the HC. The patients in the NC received a significantly lower mean daily oral prednisolone dose [13.2 (4.7) vs. 15.3 (6.6) mg/day, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001], and had lower frequencies of rejections (36% vs. 57%, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and CMV infection (54% vs. 63%, P=0.071). Patients in the NC had significantly lower odds of developing PTDM, even after adjustment for age, prednisolone dose, HLA-B27 status and CMV infection (odds ratio: 0.42, 95% CI: 0.23-0.77, P=0.005). The odds of developing PTDM are more than halved over the last decade. Possible explanations are changes in immunosuppressive therapy, fewer rejections, and lower doses of steroids.

Research paper thumbnail of Fasting Plasma Glucose and Glycosylated Hemoglobin in the Screening for Diabetes Mellitus After Renal Transplantation

Transplantation, 2009

Fasting plasma glucose (fPG) is recommended to identify new-onset posttransplant diabetes mellitu... more Fasting plasma glucose (fPG) is recommended to identify new-onset posttransplant diabetes mellitus (PTDM), but an oral glucose tolerance test (OGTT) has higher diagnostic sensitivity. We aimed to assess the accuracy of fPG and glycosylated hemoglobin (HbA1c) for the selection of patients who should undergo a diagnostic OGTT 10 weeks after renal transplantation. A total of 1571 renal transplant recipients without prior diabetes underwent an OGTT 10 weeks after transplantation. Receiver operating characteristic analyses were used to identify optimal thresholds to incite further diagnostic tests. A sensitivity level of 80% was chosen for screening purpose. We diagnosed PTDM in 213 (14%) patients of whom 109 (51%) were identified by 2-hr plasma glucose more than or equal to 11.1 mmol/L alone, 35 (17%) by fPG alone, and 69 (32%) by both criteria. Receiver operating characteristic analysis revealed an area under the curve of 0.761 (95% confidence interval 0.714-0.809) for fPG and 0.817 (95% confidence interval 0.758-0.876) for HbA1c. Performing an OGTT on patients with an fPG more than or equal to 5.3 mmol/L or HbA1c more than or equal to 5.8% predicted diabetes with 81% and 83% sensitivity, requiring 49% and 41% of the patients to be tested, respectively. The combined criterion fPG more than or equal to 5.0 mmol/L and HbA1c more than or equal to 5.7%, provided a similar sensitivity (79%) from testing only 29% of the population. We conclude that patients with an fPG between 5.3 and 6.9 mmol/L or HbA1c more than or equal to 5.8%, alternatively an fPG more than or equal to 5.0 mmol/L combined with HbA1c more than or equal to 5.7% in the early posttransplant period should undergo an OGTT for diagnostic verification of PTDM.

Research paper thumbnail of Determinants of short-term changes in body composition following renal transplantation

Scandinavian Journal of Urology and Nephrology, 2009

Changes in body composition after renal transplantation (RTx) are of clinical significance, since... more Changes in body composition after renal transplantation (RTx) are of clinical significance, since increments in fat mass may contribute to glucose intolerance and cardiovascular morbidity. The aim of this study was to quantify the early changes in body composition after transplantation and identify predictors of these changes. Total and regional body composition of 102 first kidney allograft recipients were measured at transplantation and after 10 weeks using dual-energy X-ray absorptiometry. The population comprised a high proportion of pre-emptive and well-nourished kidney recipients. Multiple linear regression was used to identify predictors of change. Mean fat mass was 27.1+/-8.7% of body weight at baseline. The fat mass percentage increased by 2.2% corresponding to a 1.3 kg increase in fat mass at 10 weeks (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Fat-free mass declined by 2.5 kg (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), with no significant loss of body weight (0.9 kg, p=0.11). Age, low-tertile fat mass, plasma C-reactive protein, time on dialysis and cumulative prednisolone dose were independent predictors (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) of the increase in fat mass. Cumulative prednisolone dose was the only significant predictor of decrease in fat-free mass. Essentially the same results were found for both genders. A significant increase in fat mass occurred rapidly after RTx along with a reduction in fat-free mass despite stable body weight. Early fat mass accumulation may predispose to comorbidity, but the long-term clinical significance of these early changes remains to be explored in prospective studies.

Research paper thumbnail of Fasting Plasma Glucose in the Screening for Type 2 Diabetes in Morbidly Obese Subjects

Obesity Surgery, 2010

Background Higher mortality rates among morbidly obese (BMI of ≥40 or ≥35 kg/m 2 with weight-rela... more Background Higher mortality rates among morbidly obese (BMI of ≥40 or ≥35 kg/m 2 with weight-related comorbidities) subjects are mainly explained by comorbidities such as type 2 diabetes. As bariatric surgery ameliorates diabetes, obese diabetic subjects will receive great benefits from bariatric surgery. Screening for diabetes prior to surgical referral is therefore crucial. Methods We studied 1,253 consecutively recruited (2005)(2006)(2007)(2008) morbidly obese subjects (67% women). Among subjects without known diabetes, 70% (670/961) performed an oral glucose tolerance test (OGTT). Screen-detected diabetes was defined as fasting plasma glucose (fPG) ≥7.0 mmol/l and/or 2-h glucose concentration (2hPG) ≥ 11.1 mmol/l. Results Within the study population, 31% had diabetes, of which 8% were screen-detected. Eighty percent of those with screen-detected diabetes were diagnosed by fPG. In subjects with nondiabetic fPG concentrations, elevating the fPG cutoff value from 5.2 mmol/l to the World Health Organization's (WHO's) recommended value of 6.1 mmol/l reduced the percentage of the population needing an OGTT considerably (78-23%), but only slightly reduced the sensitivity of fPG in detecting a diabetic 2hPG concentration (100-77%). Only 7% of the patients with fPG between 6.1 and 6.9 mmol/l had a diabetic 2hPG concentration. Following the WHO's recommendations, we found that 95% of all subjects with unknown diabetes were identified. Conclusions Fasting glucose identified four out of five morbidly obese subjects with unknown diabetes. A supplemental OGTT in selected persons identified the majority of the remaining diabetic cases.

Research paper thumbnail of A 6-year prospective study on new onset diabetes mellitus, insulin release and insulin sensitivity in renal transplant recipients

Background. It is well known that both insulin resistance and insulin deficiency are involved in ... more Background. It is well known that both insulin resistance and insulin deficiency are involved in the pathogenesis of post-transplant diabetes mellitus (PTDM), but the relative importance of the two different mechanisms is still under debate. The present prospective longitudinal study was performed over 6 years to investigate the impact of impaired insulin secretion (ISec) and insulin sensitivity (IS) in the

Research paper thumbnail of Impaired glucose homeostasis in renal transplant recipients receiving basiliximab

Nephrology Dialysis Transplantation, 2010

Background. The pathogenesis of new onset diabetes after transplantation (NODAT) is multifactoria... more Background. The pathogenesis of new onset diabetes after transplantation (NODAT) is multifactorial. Suppression of regulatory T lymphocytes may have a negative impact on pancreatic β-cells. Induction with basiliximab affects reg-ulatory T-cell function and may therefore, theoretically, also affect glucose homeostasis in renal transplant recipients. Methods. All kidney recipients ≥50 years of age without diabetes mellitus transplanted from 1 January 2005 to 31 December 2007 were included in a single-centre retrospec-Impaired glucose homeostasis in renal transplant recipients receiving basiliximab 1289 by guest on March 11, 2016 http://ndt.oxfordjournals.org/ Downloaded from (IFG) versus 36.9% in the group without induction therapy (P = 0.017). In recipients with normal OGTT, the mean fasting glucose at 10 weeks was 5.18 mmol/l (SD: 0.54) in the basiliximab group (n = 65) and 4.84 mmol/l (SD: 0.64) in the no induction group (n = 82) (P = 0.001).

Research paper thumbnail of Glucose tolerance before and after renal transplantation

Nephrology Dialysis Transplantation, 2010

Renal insufficiency predisposes to insulin resistance, hyperparathyroidism and derangements in ca... more Renal insufficiency predisposes to insulin resistance, hyperparathyroidism and derangements in calcium phosphate and nitrogenous compound balance, leading to pre-transplant hyperglycaemia. These metabolic risk factors are not fully corrected after renal transplantation. The present study aimed to assess the role of pre-transplant glycaemia and the named metabolic risk factors in post-transplant hyperglycaemia [PHYG; impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes mellitus (DM)]. This is a retrospective cohort study involving 301 patients without pre-transplant DM. Measurements included a pre- and post-transplant oral glucose tolerance test (OGTT) as well as glomerular filtration rate (GFR), parathyroid hormone (PTH), phosphate, calcium and urea measured 10 weeks post-transplant. The risk of PHYG at 10 weeks post-transplant was analysed using multiple logistic regression. Ninety-three patients (31%) had PHYG (two IFG, 52 IGT, 39 DM). Variables associated with PHYG included pre-transplant 2-h glycaemia [OR 1.26, 95% CI (1.09, 1.46)] and post-transplant urea levels [OR 1.14, 95% CI (1.02, 1.27)]. Older age, non-Caucasian ethnicity, previous transplants, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=3 HLA class 1 mismatches and high prednisolone doses were likewise associated with an increased PHYG risk (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Pre-transplant glycaemia and high post-transplant levels of urea were associated with a greater risk of PHYG. This seemed to be independent of GFR, PTH, phosphate, calcium and traditional risk factors such as age and glucocorticoid load.

Research paper thumbnail of Short-term treatment with rosiglitazone improves glucose tolerance, insulin sensitivity and endothelial function in renal transplant recipients

Nephrology Dialysis Transplantation, 2005

Background. Insulin resistance (IR) contributes to the development of glucose intolerance (post-t... more 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-g 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 ¼ 0.02) and a significant decline in fasting and 2 h plasma glucose (from 6.4 to 5.8 mmol/l, P ¼ 0.01 and from 14.2 to 10.6 mmol/l, P ¼ 0.03, respectively). Furthermore, a significant improvement in endothelial function was demonstrated (AUC ACh ; from 389 to 832 AU Á min, P ¼ 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.

Research paper thumbnail of The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensitivity in man

Nephrology Dialysis Transplantation, 2007

Background. The objectives of the present study were to investigate the possible adverse effects ... more Background. The objectives of the present study were to investigate the possible adverse effects of ciclosporin A (CsA, Sandimmun Neoral Õ ) on insulin secretion and insulin sensitivity (IS) in man. Methods. A total of 11 Caucasian non-diabetic haemodialysis (HD) patients were recruited from the Norwegian transplant waiting list to participate in this study. The patients underwent two consecutive 3 h hyperglycaemic glucose clamp procedures, before and following 2 weeks of oral CsA treatment. Statistical analyses included nine patients (7M/2F, mean age 61 AE 14 years) as two patients were withdrawn due to side effects and poor compliance. First and second phase insulin secretion (Secr 1.phase and Secr 2.phase ) were estimated as area under the insulin serum concentration vs time curve (AUC) during the first 10 min and the last hour of the clamp, respectively. The IS index (ISI) was calculated as the glucose disposal rate corrected for insulin levels during the last 60 min of the procedure. Results. Secr 2.phase decreased significantly (30%) following CsA treatment (P ¼ 0.045). In contrast, no significant change was observed in the average Secr 1.phase or ISI, although relatively large interindividual differences were present. Calculation based on C-peptide concentrations gave the same results. No significant changes in body weight, dialysis status, patient medication or safety parameters were observed. Conclusions. Short-term treatment with CsA at doses used following transplantation seems to impair Secr 2.phase , but has no significant effect on Secr 1.phase , in Caucasian HD patients. The mechanism behind these findings and their possible clinical implications need further study.

Research paper thumbnail of Determinants of insulin secretion after renal transplantation

Metabolism, 2003

The high prevalence of post-transplant glucose intolerance and insulin resistance (IR) is associa... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.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.