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Critical results should be reported to the physician as soon as possible so that the physician can take the necessary follow-up actions. Failure or non-timely reporting of such results may lead to serious health damage or death to the patient. This article focusses on the reporting of results from the laboratory to the physician and discusses the bottlenecks and the separate (legal) responsibilities of the physician and the laboratory. Improving the process of the reporting and follow-up of critical results is a joint responsibility of the laboratory and the physician requesting the laboratory tests. This could be achieved by local partnership agreements.

Context: Anemia and thyroid dysfunction often co-occur, and both increase with age. Human data on relationships between thyroid disease and anemia are scarce., Objective: To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia., Design: Individual participant data meta-analysis., Setting: Sixteen cohorts participating in the Thyroid Studies Collaboration (n = 42,162)., Main Outcome Measures: Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women)., Results: Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants [overt hypothyroidism, pooled OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43), subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69 (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism, and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups., Conclusion: Higher odds of having anemia were observed in participants with both hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.

Background: To assess the expected precision of HbA1c measurements and the magnitude of HbA1c changes eliciting the advice to change treatment among diabetes care professionals., Methods: A seven-item questionnaire was sent to participants through a website. The survey focused on physicians and nurses involved in diabetes care., Results: In total, 104 physicians, 177 diabetes specialist nurses, and 248 primary care nurses responded to the survey. A large number of the nurses (44%) and only a small number of the physicians (4%) were not aware of the inherent uncertainty of HbA1c results. Nurses considered adjusting therapy based on very small changes in HbA1c whereas physicians in general adhere to 0.5% (5.5 mmol÷mol) as a clinically meaningful cut-off point. After therapy adjustment, a very small (0.1%) or no increase in HbA1c was considered to be significant enough to conclude that glucose regulation has worsened by 49% of the nurses and only 13% of the physicians., Conclusion: Significant differences exist in the interpretation of changes in HbA1c results between physicians and nurses. Nurses consider therapy changes based on very small changes in HbA1c, whereas physicians preferably agree to the clinically relevant change of 0.5% (5.5 mmol÷mol). Changing therapy based on relatively small changes in HbA1c might lead to undue adjustments in the treatment of patients with diabetes. There is a clear need for more training for all diabetes care professionals about both the clinical significance and accuracy of HbA1c measurements.

A 53-year-old woman with respiratory discomfort came to the Emergency Department. The blood smear, made because of a new thrombocytopenia, showed leukocytes with butterfly-shaped nuclei and fine cytoplasmic granulation. The diagnosis 'microgranular variant of acute promyelocytic leukemia' was made.

Background: Statins are thought to have anti-atherogenic effects beyond cholesterol lowering. One such mechanism may involve reduction of oxidative stress. The aim of our study was to investigate and to compare the oxidative stress lowering capacity of atorvastatin with that of simvastatin in patients at high risk for cardiovascular disease using conventional markers and sensitive markers measured by highly specific techniques such as liquid chromatography tandem mass spectrometry., Methods: We included 30 statin-naive patients with diabetes mellitus, and/or obesity, and/or hypertension (12 male, 18 female, mean age 44.8±11.1 years), and randomised them to receive either atorvastatin 10 mg or simvastatin 40 mg daily to obtain an equimolar cholesterol reduction. Blood and urine samples were obtained at baseline and at 1, 6 and 12 weeks., Results: Low-density lipoprotein (LDL) cholesterol and coenzyme Q10 decreased significantly in both groups. Simvastatin caused a faster initial LDL cholesterol lowering than atorvastatin (p=0.01), but the overall effect after 12 weeks of atorvastatin and simvastatin was similar. Plasma myeloperoxidase and malondialdehyde did not change during the study period in the two groups. Urinary F2-isoprostanes decreased gradually and significantly in the atorvastatin group but not in the simvastatin group, but the between-group difference was not significant. Urinary 8-hydroxy-2-deoxyguanosine did not change in the two groups.

Objectives: Hypothyroidism is associated with normocytic anaemia. Indeed, a limited number of studies have shown significant associations between free thyroxin (T4) and erythrocyte indices. These studies did not include vitamin B12, folic acid, iron and renal function in the analyses. We therefore studied the association between thyroid hormones and erythrocyte indices in a population-based cohort of older euthyroid subjects, with adjustment for major confounding parameters., Design: Data, including thyroid hormones and erythrocyte indices, are from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study on predictors and consequences of changes in health in the ageing population in the Netherlands. Multivariable linear regression analyses were applied to study the cross-sectional associations between free T4, thyroid stimulating hormone (TSH) and erythrocyte indices (haemoglobin content, haematocrit, mean cell volume (MCV) and erythrocyte count) in a euthyroid sub-sample. The final models were adjusted for vitamin B12, folic acid, iron levels and renal function., Results: In 708 euthyroid older subjects, an increase of 5pmol/L free T4 was associated with a mean increase of 0.12mmol/L or 0.19g/dL of haemoglobin, 0.068 10(12)/L erythrocytes and 0.006L/L haematocrit (P=0.007, P=0.005, P=0.001, respectively). Free T4 was not significantly associated with MCV (P>0.05). TSH appeared not to be associated with any of the erythrocyte indices (all P>0.05)., Conclusions: In a cohort of older subjects, free T4, but not TSH, was associated with erythrocyte indices, confirming the role of thyroid hormones in the regulation of erythropoiesis., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Since the discovery of the relation between increased concentrations of fast haemoglobin fractions in patients with diabetes mellitus compared to concentrations in subjects without diabetes mellitus by Samuel Rahbar and co-workers in 1969, glycated haemoglobin A1c (HbA1c) has become a "gold standard" for glucose management in patients with diabetes mellitus. Recently, HbA1c has been advocated as a diagnostic marker for diabetes mellitus, which further underlines the importance of HbA1c. There are currently more than 30 methods available on the market with an analytical performance ranging from poor to state of the art. This review describes the biochemistry of HbA1c and the concepts of analytical and biological variation with respect to the measurement of HbA1c. Subsequently, aspects regarding the discovery of HbA1c are described. In addition, an overview is given on the assays methods that are currently available for the measurement of HbA1c. Finally, recommendations for the minimally required analytical performance characteristics of the current HbA1c assays are presented., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, analysis and interpretation were formulated. Based on discussions on analyses of list mode data files and fresh MDS bone marrow samples and recent literature, the guidelines were modified. Over the years (2005-2011), the concordance between the participating centers increased indicating that the proposed guidelines contributed to a more objective, standardized FC analysis, thereby ratifying the implementation of FC in MDS., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

In the present article, we aimed to compare the cardiometabolic risk between overweight children with and without type 1 diabetes (T1DM). Therefore, data with regard to cardiometabolic risk parameters of 44 overweight Caucasian children (3-18 years) with T1DM were matched with 44 overweight peers without T1DM for sex, ethnicity, age and standard deviation score of BMI (Z-BMI). Detailed history was taken, information regarding anthropometrics and family history were collected and blood pressure was measured. Blood samples were collected for evaluation of lipid profiles (fasting in controls, non-fasting in T1DM children), alanine aminotransferase and HbA1c (in children with T1DM). It was found that overweight children with T1DM had lower median standard deviation score of waist circumference (Z-WC) as compared to the overweight control group [median, 2.0 (interquartile range, IQR, 1.5-2.3) vs. 2.6 (IQR, 2.0-2.9), P < 0.001]. After adjustment for Z-WC, in children with T1DM, median high-density lipoprotein cholesterol levels were significantly higher and median low-density lipoprotein cholesterol lower in T1DM children, as compared to their peers without T1DM [1.40 (IQR, 1.2-1.5) vs. 1.2 (IQR, 1.0-1.3) and 2.7 (IQR, 2.5-3.2) vs. 3.0 (IQR, 2.5-3.4), respectively, all P < 0.01]. When dividing children according to glycaemic status, children with suboptimal glycaemic control had higher values of triglycerides as compared to well-controlled children [1.3 (IQR, 1.0-1.8) vs. 0.96 (IQR, 0.80-1.2), P = 0.036]. In conclusion, overweight children with T1DM have a more favourable lipid profile, as compared to non-diabetic overweight controls, in spite of a higher frequency of a positive family history of CVD, T2DM and hypertension. Still, paediatricians should give extra attention to cardiometabolic risk factors within this vulnerable group, taking into account the already high cardiometabolic risk.

Background/objectives: Postprandial hyperlipidemia, which is exaggerated and prolonged in insulin-resistant individuals, has been associated with cardiovascular disease. The objective of this study was to investigate whether and how the composition, size and function of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles are affected in the postprandial state among males with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), compared with controls., Subjects/methods: A total of 14 males with T2DM, 14 with the MetS and 14 age-matched controls were given three standardized high-fat mixed meals (900 kcal; 50-g fat, 75-g carbohydrate and 35-g protein) as breakfast, lunch and dinner. Blood sampling was performed just before each meal, and 4 and 8 h after the last meal. HDL and LDL were isolated by ultracentrifugation and analyzed for their composition, particle diameter and functional properties., Results: Postprandial triglycerides levels in plasma, HDL and LDL particles increased significantly in all groups (P<0.01). Compared with the control subjects, patients with T2DM had smaller LDL particles, and in agreement, a lower cholesterol-to-protein content in both fasting and postprandial samples. A prolonged increase in susceptibility of LDL to oxidation was found in all subjects, but was most evident in T2DM. The postprandial effect on LDL oxidation was associated with an increase in LDL triglyceride (r=0.29, P<0.05). In T2DM the anti-oxidative capacity of HDL trended to impairment after the third meal., Conclusions: Postprandial increases in triglycerides, especially in T2DM, are accompanied by pro-atherosclerotic functional changes in HDL and LDL particles.

Objectives: To determine the prevalence of traditional cardiometabolic risk factors and to assess the effect of overweight/obesity on the occurrence of these risk factors in a cohort of children with type 1 diabetes mellitus (T1DM)., Study Design: Two hundred eighty-three consecutive patients (3 to 18 years of age) attending an outpatient clinic for T1DM care were included. The prevalence of cardiometabolic risk factors, the metabolic syndrome, and high alanine aminotransferase, were assessed before and after stratification for weight status., Results: Of all children (median age, 12.8 years; interquartile range, 9.9 to 16.0; median diabetes duration, 5.3 years; interquartile range, 2.9 to 8.6), 38.5% were overweight/obese (Z-body mass index > or =1.1). Overall, median HbA1c levels were 8.2% (interquartile range, 7.4 to 9.8), and HbA1c > or =7.5% was present in 73.9%. Microalbuminuria was found in 17.7%, high triglycerides (>1.7 mmol/L) in 17.3%, high LDL-cholesterol (>2.6 mmol/L) in 28.6%, low HDL-cholesterol (<1.1 mmol/L) in 21.2%, and hypertension in 13.1% of patients. In the overweight/obese children with T1DM, versus normal-weight children, a higher prevalence of hypertension (23.9% vs 5.7%), the metabolic syndrome (25.7% vs 6.3%), and alanine aminotransferase >30 IU/L (15.6% vs 4.5%) was found (all P < .05)., Conclusions: Overweight/obesity and cardiometabolic risk factors were highly prevalent in a pediatric cohort with T1DM. Hypertension, the metabolic syndrome, and high alanine aminotransferase were significantly more prevalent in overweight/obese compared with normal-weight children with T1DM., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objectives: To examine the effect of sampling site on levels of free thyroxine (fT4) and thyrotropin (TSH)., Design and Methods: fT4 and TSH were determined by a current immuno-assay in paired samples of capillary and venous blood drawn from 30 euthyroid adults., Results: Mean levels of fT4 and TSH did not differ significantly between capillary and venous blood; capillary and venous levels correlated well and did not differ significantly from unity., Conclusions: Sampling site does not influence levels of fT4 and TSH., (2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to test whether fasting or postprandial cholesteryl ester transfer protein (CETP) concentrations are associated with postprandial changes in high-density lipoprotein cholesterol (HDL-c) concentrations after fat-rich or carbohydrate-rich meals. Postmenopausal women (76 with normal glucose metabolism [NGM], 41 with type 2 diabetes mellitus [T2DM], and 38 T2DM women with statin therapy [T2DM-ST]) received 2 consecutive fat-rich or carbohydrate-rich meals on separate occasions. Linear regression analysis was performed to assess the associations of fasting CETP and postprandial changes of CETP with postprandial changes in HDL-c. Mean plasma HDL-c concentrations decreased significantly after the fat-rich meals: 0.18 +/- 0.09 mmol/L in NGM, 0.16 +/- 0.09 mmol/L in T2DM, and 0.14 +/- 0.08 mmol/L in T2DM-ST women. This effect was smaller after using carbohydrate-rich meals: 0.12 +/- 0.09 mmol/L in the NGM, 0.12 +/- 0.08 mmol/L in the T2DM, and 0.10 +/- 0.05 mmol/L in the T2DM-ST study group. Higher fasting but not postprandial CETP concentrations were associated with a larger postprandial decrease in HDL-c (beta -0.034; 95% confidence interval, -0.067 to -0.001) after the fat-rich meals. This association was independent of the postprandial increase in triglycerides and similar among the 3 study groups. A high fasting CETP concentration may contribute to the postprandial atherogenic lipoprotein profile in postmenopausal women by decreasing HDL-c after fat-rich meals. This effect is independent from the postprandial increase in triglycerides., (Copyright 2010 Elsevier Inc. All rights reserved.)

Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n=27) and without albuminuria (NA, n=48) and controls (CO, n=28). MMP-8 and -9 levels were highest in UA patients (P<0.01). Of UA patients, 93% had at least one MMP increased, compared to 78% of NA patients and 46% of CO (P=0.001). Age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c and renal function were determinants of MMP-8 and -9 (P<0.05). In summary, MMP-8 and -9 are highest in T2DM UA patients. MMP-9, showed the strongest associations with clinical parameters related to DN., (2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Salivary cortisol is unaffected by cortisol binding globulin and reflects free serum cortisol as compared to total serum cortisol., Aim: The aim of the present study was to compare the salivary cortisol response with the serum cortisol response in a low-dose (1-microg) ACTH test in a clinical setting and to determine the optimal cut-off value of salivary cortisol as an alternative to serum cortisol., Material/subjects and Methods: We measured serum and salivary cortisol responses to iv administration of 1-microg ACTH in 51 patients (17 males) referred to the Department of Clinical Chemistry for ACTH-testing. Serum cortisol was assessed before, 20, and 30 min after ACTH-administration, and salivary cortisol was assessed before and 30 min after ACTH administration., Results: Mean cortisol at baseline, 20, and 30 min were 0.44 micromol/l (SD: 0.22), 0.64 micromol/l (SD: 0.24), and 0.70 micromol/l (SD: 0.25), respectively. Median basal salivary cortisol was 8.4 nmol/l [interquartile range (IQR): 3.8-14.2]. Salivary cortisol at 30 min equaled 35.9 nmol/l (IQR: 21.1-46.2). Basal salivary cortisol was significantly correlated with salivary cortisol at 30 min (r=0.53; p<0.001). Salivary cortisol at 30 min of 23.5 nmol/l had a sensitivity and specificity of 78.1% and 70.0%, respectively as compared to the serum cortisol cut-off values of >0.50 micromol/l., Conclusions: The salivary low-dose ACTH-test yields more dynamic responses than serum cortisol. However, the sensitivity and specificity of salivary cortisol are too low to be adequate as an alternative to the serum cortisol measurements. In women on estrogen therapy, however, the use of salivary cortisol might be superior to serum cortisol.

The criteria for the diagnosis of chronic lymphocytic leukaemia (CLL) have recently been changed, with the absolute number of monoclonal B cells instead of the total number of lymphocytes now important. CLL is diagnosed when the number of monoclonal B cells with the characteristic CLL phenotype in peripheral blood exceeds 5 x 10(9)/l; fewer than 5 x 10(9)/l of monoclonal B cells with the characteristic CLL phenotype present in peripheral blood leads to a diagnosis of monoclonal B-cell lymphocytosis (MBL): a new diagnostic entity. The prevalence of MBL is estimated to be 3% and has a relatively mild course with a progression rate from MBL to CLL of 1-2% per year. After a single evaluation by a haematologist to exclude lymphadenopathy, organomegaly and infection as causes of the lymphocytosis, patients with MBL need only be evaluated once annually by their general practitioner for measurement of the blood lymphocyte count and referral in case of progression.

Objectives: To examine the effect of blood anticoagulation type on the myeloperoxidase (MPO) concentration., Design and Methods: MPO was measured in EDTA-plasma and matched heparin-plasma and serum samples collected from healthy volunteers., Results: MPO concentrations in heparin-plasma and serum were higher than in EDTA-plasma (both P<0.001). MPO in EDTA-plasma was not significantly correlated with MPO in either heparin-plasma or serum., Conclusions: For MPO measurements, EDTA-plasma is the preferred specimen as it appears unaffected by ex vivo release of MPO from leukocytes.

Objectives: To assess the prevalence of the metabolic syndrome (MetS) in overweight/obese children and adolescents of an out-patient clinic, and to compare two definitions of MetS in adolescents., Methods: In total, 528 overweight / obese children (3-16 years), of multi-ethnic origin, underwent an oral glucose tolerance test, blood collections and anthropometric measurements. In children <10 years, MetS was assessed according to child-specific cut-off values (MetS-child). In adolescents, MetS-child and MetS-adolescent (the recommendation of the International Diabetes Federation for adolescents) were compared., Results: The prevalence of MetS-child within the cohort (median age 11.3, range 3.1-16.4 yrs) was 18.6% (children <10 years vs. adolescents: 14.1% vs. 20.7%, P=0.073). Insulin resistance was present in 47.7% (children <10 years vs. adolescents: 21.8% vs. 60.1%, P<0.001). MetS-child was highly prevalent, and not statistically significant between age groups. In adolescents, the prevalence of MetS-adolescent was higher than MetS-child (33.2% vs. 20.7%, P<0.001). The agreement between the MetS definitions was moderate (kappa =0.51), with the agreement for the MetS-criteria for abnormal lipid levels being substantial to very good (kappa =0.71 to 0.80)., Conclusions: MetS-child was highly prevalent in overweight/obese children and adolescents. A higher prevalence of MetS according to adolescent- as compared to child-specific criteria was found.

Background: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification., Content: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques., Summary: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improve CVD risk estimation. Before MPO can be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed.

We studied the association between alanine aminotransferase (ALT) and features of the metabolic syndrome in a cohort of overweight and obese children aged 3-18 years. An oral glucose tolerance test was performed in 443 consecutive children from an obesity out-patient clinic (median age 11.2, range 3.1-18.0 years; n=240 boys) of multi-ethnic origin. The prevalence of the metabolic syndrome, insulin resistance, elevated ALT (>30 IU/L), and the association of ALT with (components of) the metabolic syndrome was assessed. The metabolic syndrome was present in 26.9%. Elevated ALT levels were found in 20.3%, with a higher prevalence in boys than in girls (25.8% versus 13.8%, P<0.001). ALT was associated with the prevalence of the metabolic syndrome, insulin resistance, high triglycerides, and low HDL-cholesterol after adjustment for gender, age, and BMI. In conclusion, elevated ALT levels were highly prevalent and associated with the metabolic syndrome, insulin resistance, high triglycerides, and low HDL-cholesterol in an obese multiethnic pediatric population.

Background/objective: Early insulin secretion following a meal is representative for normal physiology and may depend on meal composition. To compare the effects of a fat-rich and a carbohydrate-rich mixed meal on insulinogenic index as a measure of early insulin secretion in normoglycemic women (NGM) and in women with type 2 diabetes mellitus (DM2), and to assess the relationship of anthropometric and metabolic factors with insulinogenic index., Subjects/methods: Postmenopausal women, 76 with NGM and 64 with DM2, received a fat-rich meal and a carbohydrate-rich meal on separate occasions. Early insulin response was estimated as insulinogenic index ( big up tri, Deltainsulin(0-30 min)/ big up tri, Deltaglucose(0-30 min)) for each meal. Associations of fasting and postprandial triglycerides, body mass index, waist and hip circumference and alanine aminotransferase with insulinogenic indices were determined., Results: Women with NGM present with higher insulinogenic index than women with DM2. The insulinogenic index following the fat-rich meal ( big up tri, DeltaI(30)/ big up tri, DeltaG(30) (fat)) was higher than the index following the carbohydrate-rich meal (big up tri, DeltaI(30)/ big up tri, DeltaG(30) (CH)) (P<0.05 in women with DM2, and not significant in women with NGM). In women with DM2, homeostasis model assessment for insulin resistance was positively associated with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (CH). In women with NGM, waist circumference was independently and inversely associated with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (fat) and with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (CH); hip circumference was positively associated with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (fat)., Conclusions: The insulinogenic index following the fat-rich meal was higher than following the isocaloric carbohydrate-rich meal, which might favorably affect postprandial glucose excursions, especially in women with DM2. The association between a larger waist circumference and a lower meal-induced insulinogenic index in women with NGM requires further mechanistic studies.

Background: Differences in prevalence of cardiometabolic risk factors between different ethnic groups are largely unknown. We determined the variation in cardiometabolic risk profile according to ethnicity in a cohort overweight/obese Dutch children., Methods: An oral glucose tolerance test was performed in 516 overweight/obese Dutch children of multi-ethnic origin, attending an obesity out-patient clinic of an urban general hospital (mean age 10.6 +/- 3.2; 55.2% boys). Anthropometric parameters and blood samples were collected, and the prevalence of (components of) the metabolic syndrome (MetS) and insulin resistance were determined in each ethnic group., Results: Major ethnic groups were Dutch native (18.4%), Turkish (28.1%), and Moroccan (25.8%). The remaining group (27.7%) consisted of children with other ethnicities. Turkish children had the highest mean standardized BMI compared to Dutch native children (P < 0.05). As compared to Moroccan children, they had a higher prevalence of MetS (22.8% vs. 12.8%), low HDL-cholesterol (37.9% vs. 25.8%), hypertension (29.7% vs. 18.0%) and insulin resistance (54.9% vs. 37.4%, all P < 0.05). Although Turkish children also had higher prevalences of forementioned risk factors than Dutch native children, these differences were not statistically significant. Insulin resistance was associated with MetS in the Turkish and Moroccan subgroup (OR 6.6; 95%CI, 2.4-18.3 and OR 7.0; 95%CI, 2.1-23.1, respectively)., Conclusion: In a Dutch cohort of overweight/obese children, Turkish children showed significantly higher prevalences of cardiometabolic risk factors relative to their peers of Moroccan descent. The prospective value of these findings needs to be established as this may warrant the need for differential ethnic-specific preventive measures.

Both postprandial hyperglycemia and hypertriglyceridemia have been identified as risk markers for cardiovascular disease, but parameters associated with these postprandial responses are largely unknown. The objective was to assess whether usually measured clinical and biochemical parameters can predict postprandial glucose and triglyceride responses and whether these responses are associated with each other. Postmenopausal women, 76 with normal glucose metabolism (NGM) and 41 with type 2 diabetes mellitus (T2DM), received 2 consecutive fat-rich meals and carbohydrate-rich meals on separate occasions. Blood samples were taken before and at t = 1, 2, 4, 6, and 8 hours after breakfast; lunch was given at t = 4 hours. Regression analysis was performed with incremental area under the postprandial triglyceride curve (triglyceride-iAUC) and glucose curve (glucose-iAUC) after fat-rich and carbohydrate-rich meals, respectively. In women with NGM, fasting triglycerides, hemoglobin A(1c), total cholesterol, and, inversely, high-density lipoprotein cholesterol were independently associated with triglyceride-iAUC; and age and fasting triglycerides were independently associated with glucose-iAUC. In women with T2DM, fasting triglycerides were independently associated with triglyceride-iAUC, whereas hemoglobin A(1c) and fasting glucose were stronger than fasting triglycerides associated with glucose-iAUC. Glucose-iAUC and triglyceride-iAUC were associated with each other in women with T2DM, but not in those with NGM. The association between glucose-iAUC and triglyceride-iAUC in women with T2DM and the association of fasting triglycerides with both glucose-iAUC and triglyceride-iAUC in NGM and T2DM suggest a common underlying mechanism for postprandial increments in glucose and triglycerides, especially in T2DM. Commonly measured clinical and biochemical parameters can only partly explain postprandial glucose and triglyceride excursions.

Patients with type 2 diabetes mellitus (DM2) have an increased risk of cardiovascular disease (CVD). Myeloperoxidase (MPO), expressed in leukocytes and released upon activation, is associated with CVD and endothelial dysfunction. Postprandial leukocyte recruitment and activation with subsequent MPO release may contribute to atherosclerosis and CVD. We hypothesized that MPO may increase in the postprandial state because of postprandial leukocyte recruitment and/or activation, especially in subjects with DM2. One hundred postmenopausal women, aged 50 to 65 years (66 with normal glucose metabolism [NGM] and 34 with DM2), received 2 consecutive fat-rich meals and 2 consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before (t = 0) and at 2, 4, and 8 hours after breakfast; lunch was given at t = 4. Plasma MPO concentration was measured by sandwich enzyme-linked immunosorbent assay. The number of leukocytes in fasting blood samples was higher in DM2 compared with NGM (6.1 +/- 1.4 and 5.4 +/- 1.2 x 10(9)/L, respectively; P < .05). Baseline MPO concentration did not significantly differ between NGM and DM2 (51.4 +/- 12.9 and 54.5 +/- 18.4 mug/L, respectively; P = .39). Baseline MPO was positively associated with leukocytes (r = 0.20, P < .05) and inversely associated with high-density lipoprotein cholesterol (r = -0.22, P < .05). Leukocytes increased from 5.0 +/- 1.5 to 6.1 +/- 1.5 x 10(9)/L and from 5.8 +/- 1.4 to 6.6 +/- 1.4 x 10(9)/L in NGM and DM2, respectively (both P < .01), after the fat-rich meals. In contrast to our hypothesized increase in MPO, we found a significant decrease in MPO in NGM (both meal types) and DM2 (fat-rich meals only). Our findings provide no support to our initial hypothesis that meal-induced release of MPO might be a mechanism that contributes to CVD risk.

The present study aimed to compare the associations of postprandial glucose (ppGL) and postprandial triglycerides (ppTG) with carotid intima media thickness (cIMT) in women with normal glucose metabolism (NGM) and type 2 diabetes (DM2). Post-menopausal women (76 with NGM, 78 with DM2), received two consecutive fat-rich and two consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before and 1, 2, 4, 6 and 8h following breakfast; lunch was given at t=4. Ultrasound imaging of the carotid artery was performed to measure cIMT. In women with NGM, an increase of 1.0 mmol/l glucose following the fat-rich meals was associated with a 50 microm cIMT increase (p=0.04), and following the carbohydrate meals, an increase of 1.8 mmol/l glucose was associated with a 50 microm larger cIMT (p=0.08). These associations were not explained by classical cardiovascular risk factors. However, no association between ppGL and cIMT was found in women with DM2 and ppTG were not associated with cIMT. The association between ppGL and cIMT in normoglycaemic women suggests that ppGL in the normal range is a marker or a risk factor for atherosclerosis. Postprandial glucose levels might be a better indicator of risk than post-OGTT glucose levels or triglyceride levels.

Objective: We studied acute changes in markers of glycoxidative and lipoxidative stress, including oxidized LDL, N(epsilon)-(carboxyethyl)-lysine (CEL), N(epsilon)-(carboxymethyl)-lysine (CML), and 3-deoxyglucosone (3DG), following two consecutive meals., Research Design and Methods: Postmenopausal women (27 with normal glucose metabolism [NGM], 26 with type 2 diabetes) received two consecutive fat-rich meals and two consecutive carbohydrate-rich meals on two occasions. Glucose and triglyceride concentrations were measured at baseline and 1, 2, 4, 6, and 8 h following breakfast; lunch was given at 4 h. Oxidized LDL-to-LDL cholesterol ratio, CEL, CML, and 3DG were measured at baseline and at 8 h., Results: Fasting oxidized LDL-to-LDL cholesterol ratio, 3DG, and CML were higher in women with type 2 diabetes compared with women with NGM and were comparable to the postprandial values at 8 h in NGM. Postprandial rises in the oxidized LDL-to-LDL cholesterol ratio and 3DG were similar in both groups. However, the oxidized LDL-to-LDL cholesterol ratio increased more after the fat-rich meals, whereas CML and 3DG increased more after the carbohydrate-rich meals. After the fat-rich meals, the increase in the oxidized LDL-to-LDL cholesterol ratio correlated with postprandial triglycerides, whereas the increase in 3DG was correlated with postprandial glucose., Conclusions: The acute changes in markers of glycoxidative and lipoxidative stress in both type 2 diabetes and NGM suggest that postabsorptive oxidative stress may partly underlie the association of postprandial derangements and cardiovascular risk.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with the metabolic syndrome and type 2 diabetes. Evidence is now accumulating that NAFLD is associated with obesity and diabetes and may serve as a predictor of cardiovascular disease. Although at present, treatment of the individual risk factors pertinent to NAFLD is advocated, novel therapies are emerging that may target steatosis and/or inflammation, thus ameliorating the overall cardiovascular disease risk. Long-term outcome studies need to establish whether treatment of NAFLD (and in particular which therapy) will affect the long-term outcome.

Aims: To study the association between alanine aminotransferase (ALT) and the 6-year risk of the metabolic syndrome in a population-based study in Caucasian men and women., Methods: The association of ALT with the 6-year risk of the metabolic syndrome in 1097 subjects, aged 50-75 years, was assessed in the Hoorn Study with logistic regression analysis. Subjects with the metabolic syndrome at baseline, defined according to the Adult Treatment Panel III of the National Cholesterol Education Program, were excluded., Results: After 6.4 (range 4.4-8.1) years follow-up, 226 subjects (20.6%) had developed the metabolic syndrome. The odds ratio (95% confidence interval) for developing the metabolic syndrome, adjusted for age, sex, alcohol intake and follow-up duration was 2.25 (1.50-3.37) for subjects in the upper tertile compared with those in the lower tertile of ALT. This association persisted after additional adjustment for all the baseline metabolic syndrome features [1.62 (1.02-2.58)]. Among the individual components of the metabolic syndrome, ALT was significantly associated only with fasting plasma glucose at follow-up., Conclusions: These data suggest that ALT is associated with risk of the metabolic syndrome in a general population of middle-aged Caucasian men and women, further strengthening the role of ALT as an indicator for future metabolic derangement. These findings warrant further studies to elucidate the role of non-adipose tissue fat accumulation in the pathogenesis of complications related to the metabolic syndrome.

Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50-75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92-1.83), 1.40 (1.09-1.81) and 2.04 (1.35-3.10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21-2.92) and 1.75 (1.12-2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.