Post-bariatric pregnancy is associated with vitamin K1 deficiency, a case control study.

BACKGROUND: Maternal obesity is associated with adverse outcome for pregnancy and childbirths. While bariatric surgery may improve fertility and reduce the risk of certain pregnancy-related complications such as hypertension and gestational diabetes mellitus, there is a lack of evidence on the optimal nutritional monitoring and supplementation strategies in pregnancy following bariatric surgery. We aimed to assess the impact of bariatric surgery on micronutrients in post-bariatric pregnancy and possible differences between gastric bypass surgery and sleeve gastrectomy. METHODS: In this prospective case control study, we recruited 204 pregnant women (bariatric surgery n = 59 [gastric bypass surgery n = 26, sleeve gastrectomy n = 31, missing n = 2] and controls n = 145) from Akershus university hospital in Norway. Women with previous bariatric surgery were consecutively invited to study participation at referral to the clinic for morbid obesity and the controls were recruited from the routine ultrasound screening in gestational week 17-20. A clinical questionnaire was completed and blood samples were drawn at mean gestational week 20.4 (SD 4.5). RESULTS: The women with bariatric surgery had a higher pre-pregnant BMI than controls (30.8 [SD 6.0] vs. 25.2 [5.4] kg/m2, p < 0.001). There were no differences between groups regarding maternal weight gain (bariatric surgery 13.3 kg (9.6) vs. control 14.8 kg (6.5), p = 0.228) or development of gestational diabetes (n = 3 [5%] vs. n = 7 [5%], p = 1.000). Mean levels of vitamin K1 was lower after bariatric surgery compared with controls (0.29 [0.35] vs. 0.61 [0.65] ng/mL, p < 0.001). Multiadjusted regression analyses revealed an inverse relationship between bariatric surgery and vitamin K1 (B -0.26 ng/mL [95% CI -0.51, -0.04], p = 0.047) with a fivefold increased risk of vitamin K1 deficiency in post-bariatric pregnancies compared with controls (OR 5.69 [1.05, 30.77] p = 0.044). Compared with sleeve gastrectomy, having a previous gastric bypass surgery was associated with higher risk of vitamin K1 deficiency (OR 17.1 [1.31, 223.3], p = 0.030). CONCLUSION: Post-bariatric pregnancy is negatively associated with vitamin K1 with a higher risk of vitamin K1 deficiency in pregnancies after gastric bypass surgery compared with after sleeve gastrectomy. Vitamin K1 deficiency in post-bariatric pregnancy have potential risk of hypocoaguble state in mother and child and should be explored in future studies.

Weight-loss drugs - for whom, how, how long? / Vektreduserende medisiner ­ for hvem, hvordan, hvor lenge?

Drug treatment of obesity is undergoing a scientific revolution, and it can be hard to keep up. Two relatively new drugs that suppress hunger and increase feelings of satiety can now be prescribed by all Norwegian doctors.

Serglycin Is Involved in Adipose Tissue Inflammation in Obesity.

Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn +/+ and Srgn -/- mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn +/+ and Srgn -/- mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn -/- mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn -/- compared with Srgn +/+ mice. Further, Srgn -/- mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

m6A Regulators in Human Adipose Tissue - Depot-Specificity and Correlation With Obesity.

Background: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications on mRNA influencing mRNA metabolism. There is emerging evidence for its implication in metabolic disease. No comprehensive analyses on gene expression of m6A regulators in human adipose tissue, especially in paired adipose tissue depots, and its correlation with clinical variables were reported so far. We hypothesized that inter-depot specific gene expression of m6A regulators may differentially correlate with clinical variables related to obesity and fat distribution. Methods: We extracted intra-individually paired gene expression data (omental visceral adipose tissue (OVAT) N=48; subcutaneous adipose tissue (SAT) N=56) of m6A regulators from an existing microarray dataset. We also measured gene expression in another sample set of paired OVAT and SAT (N=46) using RT-qPCR. Finally, we extracted existing gene expression data from peripheral mononuclear blood cells (PBMCs) and single nucleotide polymorphisms (SNPs) in METTL3 and YTHDF3 from genome wide data from the Sorbs population (N=1049). The data were analysed for differential gene expression between OVAT and SAT; and for association with obesity and clinical variables. We further tested for association of SNP markers with gene expression and clinical traits. Results: In adipose tissue we observed that several m6A regulators (WTAP, VIRMA, YTHDC1 and ALKBH5) correlate with obesity and clinical variables. Moreover, we found adipose tissue depot specific gene expression for METTL3, WTAP, VIRMA, FTO and YTHDC1. In PBMCs, we identified ALKBH5 and YTHDF3 correlated with obesity. Genetic markers in METTL3 associate with BMI whilst SNPs in YTHDF3 are associated with its gene expression. Conclusions: Our data show that expression of m6A regulators correlates with obesity, is adipose tissue depot-specific and related to clinical traits. Genetic variation in m6A regulators adds an additional layer of variability to the functional consequences.

Assessing Life Stress: A Critical Priority in Obesity Research and Treatment.

Significant childhood adversity and chronic life stress are highly prevalent in patients with severe obesity. Such stress has been found to increase risk of adulthood obesity by up to 50%, and it can also substantially degrade the effectiveness of evidence-based treatments for this chronic disease condition. Despite general appreciation of these facts, though, stress is not frequently measured in obesity research or routinely assessed during treatment for obesity or obesity-related complications. To address this important issue, we describe several validated tools that can be used for assessing life stress and discuss how information obtained from these instruments can be integrated into obesity treatment and research. Given the documented relevance of stress for obesity, we argue that stress assessment and management should be included in clinical treatments for obesity and that stress should be routinely measured in studies examining the long-term effects of obesity and obesity treatment.

Gastric bypass versus sleeve gastrectomy in patients with type 2 diabetes (Oseberg): a single-centre, triple-blind, randomised controlled trial.

BACKGROUND: For patients with obesity and type 2 diabetes, weight loss improves insulin sensitivity and ß-cell function, and can induce remission of diabetes. The comparative efficacy of various bariatric procedures for the remission of type 2 diabetes has not been fully elucidated. We aimed to compare the effects of the two most common bariatric procedures, gastric bypass and sleeve gastrectomy, on remission of diabetes and ß-cell function. METHODS: We conducted a single-centre, triple-blind, randomised trial at Vestfold Hospital Trust (Tønsberg, Norway), in which patients (aged ≥18 years) with type 2 diabetes and obesity were randomly assigned (1:1) to receive gastric bypass or sleeve gastrectomy (the Oseberg study). Randomisation was performed with a computerised random number generator and a block size of 10. Treatment allocation was masked from participants, study personnel, and outcome assessors and was concealed with sealed opaque envelopes. Surgeons used identical skin incisions during both surgeries and were not involved in patient follow-up. The primary clinical outcome was the proportion of participants with complete remission of type 2 diabetes (HbA1c of ≤6·0% [42 mmol/mol] without the use of glucose-lowering medication) at 1 year after surgery. The primary physiological outcome was disposition index (a measure of ß-cell function) at 1 year after surgery, as assessed by an intravenous glucose tolerance test. Primary outcomes were analysed in the intention-to-treat and per-protocol populations. This trial is ongoing and closed to recruitment, and is registered with ClinicalTrials.gov, NCT01778738. FINDINGS: Between Oct 15, 2012, and Sept 1, 2017, 1305 patients who were preparing for bariatric surgery were screened, of whom 319 consecutive patients with type 2 diabetes were assessed for eligibility. 109 patients were enrolled and randomly assigned to gastric bypass (n=54) or sleeve gastrectomy (n=55). 107 (98%) of 109 patients completed 1-year follow-up, with one patient in each group withdrawing after surgery (per-protocol population). In the intention-to-treat population, diabetes remission rates were higher in the gastric bypass group than in the sleeve gastrectomy group (risk difference 27% [95% CI 10 to 44]; relative risk [RR] 1·57 [1·14 to 2·16], p=0·0054); results were similar in the per-protocol population (risk difference 27% [95% CI 10 to 45]; RR 1·57 [1·14 to 2·15], p=0·0036). In the intention-to-treat population, disposition index increased in both groups (between-group difference 55 [-111 to 220], p=0·52); results were similar in the per-protocol population (between-group difference 21 [-214 to 256], p=0.86). In the gastric bypass group, ten of 54 participants had early complications and 17 of 53 had late side-effects. In the sleeve gastrectomy group, eight of 55 participants had early complications and 22 of 54 had late side-effects. No deaths occurred in either group. INTERPRETATION: Gastric bypass was found to be superior to sleeve gastrectomy for remission of type 2 diabetes at 1 year after surgery, and the two procedures had a similar beneficial effect on ß-cell function. The use of gastric bypass as the preferred bariatric procedure for patients with obesity and type 2 diabetes could improve diabetes care and reduce related societal costs. FUNDING: Morbid Obesity Centre, Vestfold Hospital Trust.

Single-centre, triple-blinded, randomised, 1-year, parallel-group, superiority study to compare the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and ß-cell function in subjects with morbid obesity: a protocol for the Obesity surgery in Tønsberg (Oseberg) study.

INTRODUCTION: Bariatric surgery is increasingly recognised as an effective treatment option for subjects with type 2 diabetes and obesity; however, there is no conclusive evidence on the superiority of Roux-en-Y gastric bypass or sleeve gastrectomy. The Oseberg study was designed to compare the effects of gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and ß-cell function. METHODS AND ANALYSIS: Single-centre, randomised, triple-blinded, two-armed superiority trial carried out at the Morbid Obesity Centre at Vestfold Hospital Trust in Norway. Eligible patients with type 2 diabetes and obesity were randomly allocated in a 1:1 ratio to either gastric bypass or sleeve gastrectomy. The primary outcome measures are (1) the proportion of participants with complete remission of type 2 diabetes (HbA1c≤6.0% in the absence of blood glucose-lowering pharmacologic therapy) and (2) ß-cell function expressed by the disposition index (calculated using the frequently sampled intravenous glucose tolerance test with minimal model analysis) 1 year after surgery. ETHICS AND DISSEMINATION: The protocol of the current study was reviewed and approved by the regional ethics committee on 12 September 2012 (ref: 2012/1427/REK sør-øst B). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences. Participants will receive a summary of the main findings. TRIAL REGISTRATION NUMBER: NCT01778738;Pre-results.

Associations between Lifetime Adversity and Obesity Treatment in Patients with Morbid Obesity.

BACKGROUND: Bariatric surgery is associated with greater and more sustainable weight loss compared with lifestyle intervention programs. On the other hand, bariatric surgery may also be associated with physical and psychosocial complications. The influence of psychological evaluation on treatment choice, however, is not known. We aimed to examine variables associated with treatment choice and, specifically, if self-reported lifetime adversity influenced obesity treatment, i.e. bariatric surgery, high-intensive lifestyle treatment or low-intensive lifestyle treatment in primary care. METHODS: We consecutively included 924 patients from the registry study of patients with morbid obesity at Akershus University Hospital, Lørenskog, Norway. Treatment selection was made through a shared decision-making process. Self-reported lifetime adversity was registered by trained personnel. Logistic regression models were used to assess the associations between obesity treatment and possible predictors. RESULTS: Patients who chose bariatric surgery were more likely to have type 2 diabetes (DM2) compared with patients who chose lifestyle treatment (bariatric surgery: 35%, high-intensive lifestyle treatment: 26%, and low-intensive lifestyle treatment: 26%; p = 0.035). Patients who chose bariatric surgery were less likely than patients who chose lifestyle intervention to report lifetime adversity (bariatric surgery: 39%, high-intensive lifestyle treatment: 47%, and low-intensive lifestyle treatment: 51%; p = 0.004). After multivariable adjustments, increasing BMI, having DM2, and joint pain were associated with choosing bariatric surgery over non-surgical obesity treatment (odds ratio [95% CI]: BMI 1.03 [1.01-1.06], DM2 1.47 [1.09-1.99], and joint pain 1.46 [1.08-1.96]). Self-reported lifetime adversity was furthermore associated with lower odds of choosing bariatric surgery in patients with morbid obesity (0.67 [0.51-0.89]). CONCLUSION: This study shows that increasing BMI, DM2, and joint pain were all associated with treatment choice for obesity. In addition, self-reported lifetime adversity was associated with the patients' treatment choice for morbid obesity. Consequently, we suggest that decisions concerning obesity treatment should include dialogue-based assessments of the patients' lifetime adversity.

The usage of fasting glucose and glycated hemoglobin for the identification of unknown type 2 diabetes in high risk patients with morbid obesity.

BACKGROUND: In spite of increased vigilance of undiagnosed type 2 diabetes (DM2), the prevalence of unknown DM2 in subjects with morbid obesity is not known. AIM: To assess the prevalence of undiagnosed DM2 and compare the performance of glycated A1c (HbA1c) and fasting glucose (FG) for the diagnosis of DM2 and prediabetes (preDM) in patients with morbid obesity. PATIENTS AND METHODS: We measured fasting glucose and HbA1c in 537 consecutive patients with morbid obesity without previously known DM2. RESULTS: A total of 49 (9%) patients with morbid obesity had unknown DM2 out of which 16 (33%) fulfilled both the criteria for HbA1c and FG. Out of 284 (53%) subjects with preDM, 133 (47%) fulfilled both the criteria for HbA1c and FG. Measurements of agreement for FG and HbA1c were moderate for DM2 (κ = 0.461, p < .001) and fair for preDM (κ = 0.317, p < .001). Areas under the curve for FG and HbA1c in predicting unknown DM2 were 0.970 (95% CI 0.942, 0.998) and 0.894 (95% CI 0.837, 0.951) respectively. The optimal thresholds to identify unknown DM2 were FG ≥6.6 mmol/L and HbA1c ≥ 6.1% (43 mmol/mol). CONCLUSIONS: The prevalence of DM2 remains high and both FG and HbA1c identify patients with unknown DM2. FG was slightly superior to HbA1c in predicting and separating patients with unknown DM2 from patients without DM2. We suggest that an FG ≥6.6 mmol/L or an HbA1c ≥6.1% (43 mmol/mol) may be used as primary cut points for the identification of unknown DM2 among patients with morbid obesity.

The association between severity of King's Obesity Staging Criteria scores and treatment choice in patients with morbid obesity: a retrospective cohort study.

BACKGROUND: The King's Obesity Staging Criteria (KOSC) comprises of a four-graded set of health related domains. We aimed to examine whether, according to KOSC, patients undergoing bariatric surgery differed from those opting for conservative treatment. METHODS: We graded 2142 consecutive patients with morbid obesity attending our centre from 2005-10 into the following KOSC domains: airway/apnoea, body mass index (BMI), cardiovascular risk (CV-risk), diabetes mellitus, economic complications, functional limitations, gonadal dysfunction, and perceived health status/body image. Both patients and physicians agreed upon treatment choice through a shared decision making process. RESULTS: A total of 1329 (62%) patients opted for lifestyle intervention and 813 (37%) for bariatric surgery as their first treatment choice. The patients treated with bariatric surgery were younger (42 vs. 44 years, p < 0.001), had a higher BMI (45.4 vs. 43.8 kg/m2, p < 0.001) and had a lower ten year estimated CV-risk (9.4 vs. 10.7%, p = 0.004) than the lifestyle intervention group. Compared with having BMI < 40 kg/m2, BMI ≥ 40 kg/m2 was associated with 85% increased odds of bariatric surgery (OR 1.85 [95% CI 1.48, 2.30]). Conversely, patients with ≥20% ten year CV-risk, had lower odds of bariatric surgery than patients with <20% CV-risk (0.68 [0.53, 0.87]). CONCLUSION: BMI was the strongest KOSC-domain associated with subsequent bariatric surgery after a shared decision making process. Prospective studies are required to assess whether the use of KOSC can help guide patients and clinicians to identify the most appropriate choice of treatment for morbid obesity.

Early posttransplantation hyperglycemia in kidney transplant recipients is associated with overall long-term graft losses.

BACKGROUND: The association of early-onset posttransplantation hyperglycemia with long-term renal allograft survival is unknown. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Undiagnosed diabetes in kidney transplant candidates: a case-finding strategy.

BACKGROUND AND OBJECTIVES: Guidelines recommend that candidates for kidney transplantation (KTx) who do not have diabetes perform a pretransplantation oral glucose tolerance test (OGTT) when fasting plasma glucose (FPG) is <110 mg/dl (<6.1 mmol/L); however, the OGTT is potentially costly and cumbersome. We studied the role of the OGTT for diagnosing diabetes and the accuracy of FPG and glycated hemoglobin (HbA(1c)) for predicting a diabetic OGTT before KTx. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional study, 889 first single-kidney transplant candidates without diabetes, mainly white, performed an OGTT during the transplantation workup. Results were studied using receiver operating characteristic analysis. RESULTS: Of 72 (8.1%) patients with undiagnosed diabetes, only 16 (22%) had a diabetic FPG (> or =126 mg/dl [> or =7.0 mmol/L]). In patients with a nondiabetic FPG, diabetes (2-hour plasma glucose [2h-PG] > or =200 mg/dl [> or =11.1 mmol/L]) was predicted by FPG but not by HbA(1c). Performing the OGTT in patients with FPG 92 to 125 mg/dl (5.1 to 6.9 mmol/L) identified 65 (90%) patients with diabetes (16 by FPG, 49 by 2h-PG) and required seven OGTTs per patient identified. Subjecting all patients with FPG <110 mg/dl (<6.1 mmol/L) to the OGTT identified 60 (83%) patients with diabetes (16 by FPG, 44 by 2h-PG) but required 14 OGTTs per patient. CONCLUSIONS: The OGTT was paramount in finding most cases of undiagnosed diabetes before KTx. FPG but not HbA(1c) predicted a diabetic OGTT. We suggest that white KTx candidates without diabetes perform a pretransplantation OGTT when FPG is 92 to 125 mg/dl (5.1 to 6.9 mmol/L).

Impaired glucose homeostasis in renal transplant recipients receiving basiliximab.

BACKGROUND: The pathogenesis of new onset diabetes after transplantation (NODAT) is multifactorial. Suppression of regulatory T lymphocytes may have a negative impact on pancreatic beta-cells. Induction with basiliximab affects regulatory T-cell function and may therefore, theoretically, also affect glucose homeostasis in renal transplant recipients. METHODS: All kidney recipients > or =50 years of age without diabetes mellitus transplanted from 1 January 2005 to 31 December 2007 were included in a single-centre retrospective study. Immunosuppression consisted of steroids, mycophenolate mofetil and cyclosporine. Basiliximab was introduced as induction therapy 1 January 2007. An oral glucose tolerance test (OGTT) was performed in all patients 10 weeks post-transplant. RESULTS: A total of 264 patients were recruited. One hundred and thirty-four patients received basiliximab. In the basiliximab group, 51.5% developed NODAT, impaired glucose tolerance (IGT) or impaired fasting glucose (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). CONCLUSION: Use of basiliximab as induction therapy may be associated with impaired glucose homeostasis after kidney transplantation.

Glucose tolerance before and after renal transplantation.

BACKGROUND: 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)]. METHODS: 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. RESULTS: 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, >or=3 HLA class 1 mismatches and high prednisolone doses were likewise associated with an increased PHYG risk (all P < 0.05). CONCLUSIONS: 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.

Fasting plasma glucose and glycosylated hemoglobin in the screening for diabetes mellitus after renal transplantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Reduced incidence of new-onset posttransplantation diabetes mellitus during the last decade.

BACKGROUND: 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. METHODS: 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. RESULTS: 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<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<0.001], and had lower frequencies of rejections (36% vs. 57%, P<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). CONCLUSIONS: 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.