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The association between the MCM6-13910-C/T polymorphism and lactose intolerance in individuals of European descent is well known. However, the notion that having a single versus a double allelic mutation might influence one's phenotype has been hypothesized. This study investigated whether patients with the three genotypes C/C, C/T, T/T differed in response to a lactose tolerance test (LTT) in a Danish setting. Anonymized data on 603 individuals with results for both genetic test and LTT were investigated. Mean delta glucose values were plotted for the time points of the LTT (0, 15, 30, 45 and 60 min) for the C/C, C/T and T/T genotype, respectively. Further, the agreement between the three genotypes and the diagnostic interpretation of the LTT were examined using a cut-off of > 1.4 mmol/L rise in glucose. In subjects with the C/C genotype, mean glucose delta levels were markedly lower compared to both the C/T and T/T genotypes at all time points. Overall, a difference between mean glucose delta values among the C/T and T/T genotype could not be shown. Using a LTT cut-off of > 1.4 mmol/L, the proportions of lactose intolerant LTT results for each genotype were as follows: 58% among C/C, 5% among C/T, and 7% among T/T. In a Danish healthcare setting, the C/C genotype was on average associated with a smaller glucose response during a LTT when compared to the C/T and T/T genotypes. A marked difference in the LTT response among the C/T and T/T genotype was not observed. [ABSTRACT FROM AUTHOR]

Purpose: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications. Patients and methods: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p < 0.05. Results: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%. Conclusion: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings. [ABSTRACT FROM AUTHOR]

Free ionized calcium (fCa) is considered the gold standard for assessing calcium status in patients, but it is relatively expensive and is associated with several preanalytical and analytical error sources. We investigated the feasibility of using a reflex test that involves first measuring total calcium (tCa) and if out of reference range, then measure fCa, with expectation of reducing the number of fCa measurements. We used data from 1815 unique patients with concurrent measurement of fCa, tCa and albumin adjusted calcium (aCa). Patients were stratified by albumin level, and the association of fCa to tCa and aCa respectively was assessed with linear regression. The regression analysis showed the best linearity for tCa and aCa at albumin <35 g/L (R2: 0.80–0.90), and the poorest at albumin >40 g/L (R2: tCa 0.58; aCa 0.59). We examined the accuracy of hypo- and hypercalcemia classifications for tCa, aCa and the reflex test. aCa had more misclassifications of hypo- and hypercalcemia than tCa, with respectively 25% and 21%. Implementation of the reflex test would correct any false hypo- or hypercalcemia classified by tCa, leaving only false negative results corresponding to 9% of all tCa measurements. False negative results were on average 0.04 mmol/L above or below the reference range of fCa. Implementation of the reflex test reduces the number of fCa by 68% without major errors diagnosing hyper- or hypocalcemia. [ABSTRACT FROM AUTHOR]

The association between ferritin and transferrin saturation (TS), respectively, and all-cause mortality is unclear. Furthermore, the influence of concurrent inflammation has not been sufficiently elucidated. We investigated these associations and the effect of concurrently elevated C-reactive protein (CRP), and accordingly report the levels associated with lowest all-cause mortality for females and males with and without inflammation. Blood test results from 161,921 individuals were included. Statistical analyses were performed in sex-stratified subpopulations, with ferritin or TS level as continuous exposure variables, and were adjusted for age, co-morbidity and inflammation status using CRP. An interaction was used to investigate whether the effect of ferritin or TS on all-cause mortality was modified by inflammation status (CRP ≥ 10 mg/L or CRP < 10 mg/L). Low and high ferritin and TS levels were respectively associated with increased all-cause mortality in females and in males. These associations persisted with concurrent CRP ≥ 10 mg/L. The ferritin level associated with lowest mortality was 60 µg/L for females and 125 µg/L for males with CRP < 10 mg/L. It was 52 µg/L for females and 118 µg/L for males with CRP ≥ 10 mg/L. The TS level associated with lowest mortality was 33.9% for females and 32.3% for males with CRP < 10 mg/L. It was 28.7% for females and 30.6% for males with CRP ≥ 10 mg/L. Our findings can nuance clinical interpretation and further aid in defining recommended ranges for ferritin and TS. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the possible association between P-Albumin and 30-day mortality in hip fracture patients. The study is based on information from a database of hip fracture patients, established and collected at Bispebjerg University Hospital (Copenhagen, Denmark). This database includes all femoral neck (DS720), pertrochanteric (DS721) and subtrochanteric fractures (DS722) admitted to Bispebjerg Hospital between 1996 and 2012. We further identified all surgically treated hip fracture patients aged >60 years with an available P-Albumin at admission. 1856 patients were eligible for inclusion in this study (73.7% female, 26.3% male). 11.8% of these had died within 30 days. Differences between continuous variables were tested using unpaired t-tests while differences in the distribution of categorical variables were tested using chi square tests. After adjusting for co-variates in a logistic regression model, the association between P-Albumin and 30-day mortality remained increased, (OR 1.09, 95% CI 1.05;1.11 (p < 0.0001)). This study shows an increased 30-day mortality risk among surgically treated hip fracture patients with decreasing levels of P-Albumin even after adjusting for age, sex, BMI, CCI and fracture type. Routine screening of patients for hypoalbuminemia at hospital admission may be beneficial in the management of hip fracture patients. [ABSTRACT FROM AUTHOR]

Cholecystokinin (CCK) is a gut hormone which regulates gallbladder contraction and pancreatic enzyme secretion. In addition, CCK is also a major intestinal satiety signal. The knowledge about CCK in circulation, however, has been limited by difficulties in accurate measurement of the concentrations in plasma. Thus, CCK circulates in low concentrations and furthermore, it is structurally homologous to the antral hormone, gastrin, which circulates in higher concentrations. Therefore, most antibodies raised against CCK cross-react in immunoassays with gastrin. However, using highly sensitive and entirely specific in-house radioimmunoassays, which meet these challenges, we have now measured the daily concentration-variations of CCK and gastrin in plasma from young healthy men (n = 24). Plasma was sampled every third hour from each person during 24 h. The results show that the gastrointestinal secretion of both CCK and gastrin in man display significant circadian variations. [ABSTRACT FROM AUTHOR]

Hemoglobin A1c (HbA1c) is a long-term measure for glucose concentration in plasma. Since its introduction as a diabetes monitoring tool, and its more recent application as a diagnostic tool, the number of measurements of HbA1c have risen dramatically. However, HbA1c change is slow, so repeating measurements should not be done too often. We use a large, unfiltered dataset from 52,017 patients to determine the possible rate of change in HbA1c concentration. In our laboratory, the critical difference between HbA1c measurements is 8.5%. Our data show that a 1-unit HbA1c rise takes 4 weeks to occur, hence, at a HbA1c concentration around 50 mmol/mol Hgb, a critically increased HbA1c concentration cannot be determined until after 16 weeks. Conversely a critically lower HbA1c can manifest itself after 2 weeks, but after 7 weeks the dropping tendency stops. The amount of measurements that can be cancelled because they were taken sooner than 16 weeks is 23 percent. [ABSTRACT FROM AUTHOR]

Background: To examine whether time of the day has an effect on the circulating levels of metabolism parameters.Methods: Venous blood samples were obtained under standardized conditions from 24 healthy young men every third hour through 24 hours. The metabolic markers and melatonin were examined at each time-point and data were analyzed by rhythmometric statistical methods.Results: The normal 24-h rhythms of the participants were confirmed by significant oscillation of melatonin (p < 0.0001). Cosinor analysis revealed significant diurnal 24-h rhythms of five of the seven examined markers: Total cholesterol (p = 0.01, amplitude (amp) = 0.18 mmol/L) peaking in the early afternoon, Glucose (p < 0.0001, amp = 0.35 mmol/L) peaking around midnight, C-peptide (p < 0.001, amp = 360 pmol/L), triglyceride (p < 0.0001, amp = 0.37 mmol/L) peaking in the afternoon and low-density lipoprotein cholesterol (p = 0.003, amp = 0.16 mmol/L) peaking in the morning. C-peptide, triglyceride, and glucose had the highest 24-h oscillations in proportion to the reference ranges of the parameters for healthy young men. Glycated haemoglobin (HbA1c) (p = 0.07, amp = 0.57 mmol/L) and high-density lipoprotein (p = 0.09, amp = 0.06 mmol/L) did not show significant oscillations.Conclusions: When diagnosing and monitoring metabolic disorders compensation for the 24-h variation of the biochemical metabolic markers is needed especially C-peptide, triglyceride and glucose. Furthermore, the stable HbA1c level through 24 h makes it an accurate diagnostic test for diabetes mellitus. [ABSTRACT FROM AUTHOR]

Introduction. Increased mortality in patients with low serum concentrations of S-25(OH)D has been described, though no causal relationship has been shown. The aim of this cohort study was to investigate the possible association between S-25(OH)D status and all-cause mortality in 5,147 patients attending a university hospital in Denmark from 2003-2008. Methods. Serum was analyzed for ionized calcium (S-Ca2+), parathyroid hormone (S-PTH) and S-25(OH)D. Kaplan-Meier curves were used to analyze the association between S-25(OH)D quartiles, S-PTH-quartiles and all-cause mortality. Cox regression analyzed associations of age, gender, concentrations of ionized calcium, S-PTH and S-25(OH)D with all-cause mortality. Results. Log rank tests for both S-25(OH)D and S-PTH quartiles showed a significant difference across the quartiles. The Cox regression analysis showed a hazard ratio (HR) for death of 1.02 (95% CI: 1.01; 1.03) for S-PTH per pmol/L increase, 1.07 (95% CI: 1.05; 1.10) for S-25(OH)D per 10 nmol/L decrease and 0.54 (95% CI: 0.24; 1.20) for S-Ca2+ per mmol/L increase. Discussion. This study supports growing evidence, that low serum concentrations of 25(OH)D are associated with an increased all-cause mortality; however the nature of the study prevents the finding of a causal relationship. In the Cox regression analysis S-25(OH)D concentrations in the blood were inversely associated with all-cause mortality. Prospective controlled studies are needed to confirm a causal relationship between low S-25(OH)D concentrations and mortality. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the influence of time of day on the circulating concentrations of 14 frequently used clinical biochemical parameters in the Bispebjerg study of diurnal variations. Materials and methods. Venous blood samples were obtained under controlled environmental, activities and food conditions from 24 healthy young men every third hour through 24 hours, nine time points in total. At each time point, the parameters' concentrations were measured. The data were analyzed by rhythmometric statistical methods and in addition the biological variations were calculated. Results. Significant oscillation of melatonin with an amplitude (amp) of 19.84 pg/ml and a peak at 03:34 h confirmed the normal 24-hour rhythms of the participants. Potassium ( p < 0.0001, amp = 0.18 mmol/L), sodium ( p < 0.0001, amp = 1.10 mmol/L) creatine kinase ( p = 0.01, amp = 17.18 U/L), bilirubin ( p < 0.0001, amp = 2.36 μmol/L) and aspartate aminotransferase ( p < 0.0001, amp = 1.66 U/L) oscillated with gradually falling mean concentrations through the day to nadir around midnight. Urea nitrogen ( p = 0.01, amp = 0.22 mmol/L) oscillated with gradually increasing mean concentrations through the day peaking around midnight. Lactate dehydrogenase ( p < 0.0001, amp = 9.76 U/L) oscillated with gradually increasing concentrations through the early day peaking in the afternoon. Uric acid ( p = 0.03, amp = 0.013 mmol/L) oscillated with gradually increasing concentrations through the night peaking in the morning. Potassium and sodium had the highest 24-hour oscillations in proportion to the reference intervals of the parameters for healthy young men. Conclusions. In the clinical setting, diurnal variations of clinical biochemical parameters commonly used through the day and night must be considered when concentration changes in the parameters are evaluated especially potassium and sodium. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the influence of time of day on the circulating concentrations of 21 hematology parameters. Materials and methods. Venous blood samples were obtained under standardized circumstances from 24 healthy young men every third hour through 24 hours, nine time points in total. At each time point, the level of melatonin, iron, transferrin, transferrin saturation, ferritin, cobalamin, folate, red blood cells and white blood cells was measured. The data were analysed by rhythmometric statistical methods. The biological variations were calculated. Results. Significant oscillation of melatonin ( p < 0.0001) with an amplitude (amp) of 19.84 pg/ml and a peak level at 03:34 h confirmed the normal 24-hour rhythms of the participants. Erythrocytes ( p < 0.0001, amp == 0.15 × 1012/L), hemoglobin ( p < 0.0001, amp == 0.29 mmol/L), hematocrit ( p < 0.0001, amp == 0.01), iron ( p < 0.0001, amp == 4.00μmol/L), transferrin ( p == 0.03, amp == 1.41μmol/L), transferrin saturation ( p < 0.0001, amp == 6.37%) and folate ( p < 0.0001, amp == 1.55nmol/L) oscillated significantly, with gradually falling mean levels through the day to nadir around midnight. Leukocyte count ( p < 0.0001, amp == 0.78 × 109/L), neutrophils ( p == 0.001, 0.31 × 109/L), eosinophils ( p < 0.0001, amp == 0.04 × 109/L), monocytes ( p == 0.0009, amp == 0.06 × 109/L), lymphocytes ( p < 0.0001, amp == 0.49 × 109/L) oscillated significantly with gradually increasing mean levels through the day peaking at midnight. Iron, leukocytes and hemoglobin had the highest 24 hour oscillations in proportion to the reference intervals of the parameters for healthy young men. Conclusions. Biochemical screenings are biased by diurnal variations, which must be considered when blood concentrations of these parameters are interpreted in the clinical setting. [ABSTRACT FROM AUTHOR]