Glycated albumin in pregnancy: LC-MS/MS-based reference interval in healthy, nulliparous Scandinavian women and its diagnostic accuracy in gestational diabetes mellitus

Glycated albumin (GA) may be a useful biomarker of glycemia in pregnancy. The aim of this study was to establish the reference interval (RI) for GA, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in healthy, nulliparous pregnant women. In addition, we assessed the accuracy of GA and glycated hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM). Finally, we explored the prevalence of GDM in healthy nulliparas, comparing three diagnostic guidelines (WHO-1999, WHO-2013 and the Norwegian guideline). The study was carried out at Stavanger University Hospital, Norway, and included a study population of 147 pregnant nulliparous women. An oral glucose tolerance test (OGTT) was performed and used as the gold standard for GDM diagnosis. Blood samples for analysis of GA and HbA1c were collected at pregnancy week 24–28. A nonparametric approach was chosen for RI calculation, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of GA and HbA1c. The established RI for GA in 121 pregnant women was 7.1–11.6%. The area under the ROC curves (AUCs) were 0.531 (GA) and 0.627 (HbA1c). According to the WHO-1999, WHO-2013 and the Norwegian guideline, respectively, 24 (16%), 36 (24%) and 21 (14%) women were diagnosed with GDM. Only nine women (6%) fulfilled the GDM-criteria of all guidelines. In conclusion, we established the first LC-MS/MS-based RI for GA in pregnant women. At pregnancy weeks 24–28, neither GA nor HbA1c discriminated between those with and without GDM. Different women were diagnosed with GDM using the three guidelines.publishedVersio

Glycated albumin and continuous glucose monitoring metrics across pregnancy in women with pre-gestational diabetes

Introduction: Glycated albumin (GA), a biomarker reflecting short-term glycaemia, may be useful to assess glycaemic control in pregnancy. We examined the association between GA and continuous glucose monitoring (CGM) metrics across gestation. Methods: In this prospective cohort study including 40 women with pre-gestational diabetes, blood samples for analysis of GA and glycated haemoglobin A1c (HbA1c) were collected at pregnancy week 12, 20, 24, 28, 32 and 36. In the CGM-group (n = 19), CGM data were collected from first trimester until pregnancy week 36. Receiver operating characteristic (ROC) curves were used to assess the accuracy of GA and HbA1c to detect poor glycaemic control, using CGM metrics as the reference standard. This study was conducted at Stavanger University Hospital, Norway, in 2016–2018. Results: Glycaemic control improved across gestation with more time spent in target range, coinciding with decreased glycaemic variability and lower mean GA level. There was statistically significant correlation between GA and most CGM metrics. The area under the ROC curves (AUC) for detecting time in range 25% for the pregnancy glucose target 63–140 mg/dl (3.5–7.8 mmol/L) were 0.78 and 0.82 for GA, whereas AUCs of 0.60 and 0.72 were found for HbA1c, respectively. Conclusions: Higher GA levels were associated with less time spent in target range, more time spent in the above range area and increased glycaemic variability. GA was more accurate than HbA1c to detect time above range >25% and time in range <70%.publishedVersio

Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation

Background: Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels. Methods: Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013. Results: Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival. Conclusions: In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.publishedVersio

Glycated albumin in pregnancy: LC-MS/MS-based reference interval in healthy, nulliparous Scandinavian women and its diagnostic accuracy in gestational diabetes mellitus

Glycated albumin (GA) may be a useful biomarker of glycemia in pregnancy. The aim of this study was to establish the reference interval (RI) for GA, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in healthy, nulliparous pregnant women. In addition, we assessed the accuracy of GA and glycated hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM). Finally, we explored the prevalence of GDM in healthy nulliparas, comparing three diagnostic guidelines (WHO-1999, WHO-2013 and the Norwegian guideline). The study was carried out at Stavanger University Hospital, Norway, and included a study population of 147 pregnant nulliparous women. An oral glucose tolerance test (OGTT) was performed and used as the gold standard for GDM diagnosis. Blood samples for analysis of GA and HbA1c were collected at pregnancy week 24–28. A nonparametric approach was chosen for RI calculation, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of GA and HbA1c. The established RI for GA in 121 pregnant women was 7.1–11.6%. The area under the ROC curves (AUCs) were 0.531 (GA) and 0.627 (HbA1c). According to the WHO-1999, WHO-2013 and the Norwegian guideline, respectively, 24 (16%), 36 (24%) and 21 (14%) women were diagnosed with GDM. Only nine women (6%) fulfilled the GDM-criteria of all guidelines. In conclusion, we established the first LC-MS/MS-based RI for GA in pregnant women. At pregnancy weeks 24–28, neither GA nor HbA1c discriminated between those with and without GDM. Different women were diagnosed with GDM using the three guidelines

Glycated albumin in pregnancy: LC-MS/MS-based reference interval in healthy, nulliparous Scandinavian women and its diagnostic accuracy in gestational diabetes mellitus

Glycated albumin (GA) may be a useful biomarker of glycemia in pregnancy. The aim of this study was to establish the reference interval (RI) for GA, analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), in healthy, nulliparous pregnant women. In addition, we assessed the accuracy of GA and glycated hemoglobin A1c (HbA1c) in the diagnosis of gestational diabetes mellitus (GDM). Finally, we explored the prevalence of GDM in healthy nulliparas, comparing three diagnostic guidelines (WHO-1999, WHO-2013 and the Norwegian guideline). The study was carried out at Stavanger University Hospital, Norway, and included a study population of 147 pregnant nulliparous women. An oral glucose tolerance test (OGTT) was performed and used as the gold standard for GDM diagnosis. Blood samples for analysis of GA and HbA1c were collected at pregnancy week 24–28. A nonparametric approach was chosen for RI calculation, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of GA and HbA1c. The established RI for GA in 121 pregnant women was 7.1–11.6%. The area under the ROC curves (AUCs) were 0.531 (GA) and 0.627 (HbA1c). According to the WHO-1999, WHO-2013 and the Norwegian guideline, respectively, 24 (16%), 36 (24%) and 21 (14%) women were diagnosed with GDM. Only nine women (6%) fulfilled the GDM-criteria of all guidelines. In conclusion, we established the first LC-MS/MS-based RI for GA in pregnant women. At pregnancy weeks 24–28, neither GA nor HbA1c discriminated between those with and without GDM. Different women were diagnosed with GDM using the three guidelines

Neutrophil Gelatinase-Associated Lipocalin, Fibroblast Growth Factor 23, and Soluble Klotho in Long-Term Kidney Donors

BACKGROUND: The best treatment for end-stage renal disease (ESRD) is kidney transplantation. Twenty-seven percent of transplantations in Norway are from living donors. Recent studies have shown an increased risk of ESRD and increased mortality in donors. The aim of this study was to determine if the levels of the new biomarkers neutrophil gelatinase-associated lipocalin (NGAL), soluble Klotho (sKlotho), and fibroblast growth factor 23 (FGF23) are changed in kidney donors with normal kidney function defined as an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m(2) compared to patients with chronic kidney disease (CKD) stages 3-5 and healthy controls. METHODS: This is a cross-sectional, observational, single-center study including 35 kidney donors with an eGFR ≥60 ml/min/1.73 m(2) 5 years after donation, 22 patients with CKD stage 3 (eGFR 30-59 ml/min/1.73 m(2)), 18 patients with CKD stage 4 (eGFR 15-29 ml/min/1.73 m(2)), 20 patients with CKD stage 5 (eGFR <15 ml/min/1.73 m(2)), and 35 controls comparing levels of biomarkers in long-term kidney donors with those in CKD patients and healthy controls. RESULTS: The level of log NGAL was significantly higher in donors than in healthy controls (2.02 ± 0.10 vs. 1.89 ± 0.10 ng/ml; p < 0.001), and the level increased with declining kidney function. The log FGF23 level was nonsignificantly higher in donors than in controls, but it significantly increased with declining kidney function. The log sKlotho levels were significantly lower in patients with CKD stages 4 and 5 than in controls, but no difference was revealed between controls and donors. CONCLUSION: Kidney donors have significantly higher levels of NGAL than healthy controls after a median of 15 years (range 5-38). NGAL could be a valuable diagnostic marker in the future. FGF23 and sKlotho were not significantly different between donors and controls

Glycated albumin and continuous glucose monitoring metrics across pregnancy in women with pre-gestational diabetes

Introduction: Glycated albumin (GA), a biomarker reflecting short-term glycaemia, may be useful to assess glycaemic control in pregnancy. We examined the association between GA and continuous glucose monitoring (CGM) metrics across gestation. Methods: In this prospective cohort study including 40 women with pre-gestational diabetes, blood samples for analysis of GA and glycated haemoglobin A1c (HbA1c) were collected at pregnancy week 12, 20, 24, 28, 32 and 36. In the CGM-group (n = 19), CGM data were collected from first trimester until pregnancy week 36. Receiver operating characteristic (ROC) curves were used to assess the accuracy of GA and HbA1c to detect poor glycaemic control, using CGM metrics as the reference standard. This study was conducted at Stavanger University Hospital, Norway, in 2016–2018. Results: Glycaemic control improved across gestation with more time spent in target range, coinciding with decreased glycaemic variability and lower mean GA level. There was statistically significant correlation between GA and most CGM metrics. The area under the ROC curves (AUC) for detecting time in range 25% for the pregnancy glucose target 63–140 mg/dl (3.5–7.8 mmol/L) were 0.78 and 0.82 for GA, whereas AUCs of 0.60 and 0.72 were found for HbA1c, respectively. Conclusions: Higher GA levels were associated with less time spent in target range, more time spent in the above range area and increased glycaemic variability. GA was more accurate than HbA1c to detect time above range >25% and time in range <70%

Vitamin D as a risk factor for patient survival after kidney transplantation: A prospective observational cohort study

Background: Short‐term survival after kidney transplantation is excellent, but long‐term survival remains low and is equivalent to non‐end‐stage renal disease patients with many invasive malignancies. The aim of the study was to explore vitamin D status in the early phase after transplantation as a prognostic marker for long‐term graft and patient survival. Methods: All first‐time kidney transplant recipients between October 2007 and October 2012 in Norway were included. Vitamin D was measured 10 weeks post‐transplant. Information on graft failure and death was obtained from the Norwegian Renal Registry. Results: Seven hundred and sixty‐two first‐time kidney transplant recipients were included, with a median age of 57 years and a median follow‐up of 82 months. In the follow‐up period, there were 172 graft failures (23%) and 118 deaths (15%). Eighty‐six percent of the transplant recipients with sufficient vitamin D levels were alive with a well‐functioning graft after 5 years using Kaplan‐Meier survival estimates, compared with 79% and 76% of the patients with vitamin D deficiency and insufficiency, respectively (P = 0.006). Conclusion: In a nation‐wide cohort of 762 first‐time kidney transplant recipients, long‐term graft and patient survival were better in recipients with vitamin D sufficiency 10 weeks post‐transplant compared with those with vitamin D deficiency and insufficiency

Vitamin D as a risk factor for patient survival after kidney transplantation: A prospective observational cohort study

Background Short‐term survival after kidney transplantation is excellent, but long‐term survival remains low and is equivalent to non‐end‐stage renal disease patients with many invasive malignancies. The aim of the study was to explore vitamin D status in the early phase after transplantation as a prognostic marker for long‐term graft and patient survival. Methods All first‐time kidney transplant recipients between October 2007 and October 2012 in Norway were included. Vitamin D was measured 10 weeks post‐transplant. Information on graft failure and death was obtained from the Norwegian Renal Registry. Results Seven hundred and sixty‐two first‐time kidney transplant recipients were included, with a median age of 57 years and a median follow‐up of 82 months. In the follow‐up period, there were 172 graft failures (23%) and 118 deaths (15%). Eighty‐six percent of the transplant recipients with sufficient vitamin D levels were alive with a well‐functioning graft after 5 years using Kaplan‐Meier survival estimates, compared with 79% and 76% of the patients with vitamin D deficiency and insufficiency, respectively (P = 0.006). Conclusion In a nation‐wide cohort of 762 first‐time kidney transplant recipients, long‐term graft and patient survival were better in recipients with vitamin D sufficiency 10 weeks post‐transplant compared with those with vitamin D deficiency and insufficiency

Clues for early detection of autoimmune Addison's disease - myths and realities

BACKGROUND: Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. OBJECTIVE: Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. MATERIAL AND METHODS: A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. RESULTS: Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L(-1) [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L(-1) [2-442]) than in those without (81 nmol L(-1) [1-668], P < 0.001). CONCLUSION: The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis