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Background: Hyperglycaemia during and after hip surgery is associated with coagulation activation and an increased risk of venous thromboembolism. Whether lowering of glucose levels during hip surgery diminishes coagulation activation is unknown. We investigated the efficacy of the human GLP-1 analogue liraglutide to lower glucose during and after hip surgery and studied its influence on coagulation activation., Methods: A total of 37 obese subjects who underwent hip surgery were randomized to subcutaneous liraglutide or placebo for 4 consecutive days, starting one day prior to surgery. Glucose levels and coagulation indices at three fixed time-points (pre-operative, 2 h post-operative and 3 days post-operative) were measured., Results: Liraglutide reduced glucose at day three post-surgery (median glucose (IQR) liraglutide 5.5 (5.2-5.7) vs. placebo 5.8 (5.5-6.2); difference 0.3 mmol/L, P = 0.04). Changes in 6 out of 8 coagulation indices studied did not differ between the two groups. Only D-dimer levels were significantly lower in the liraglutide group at day three post-surgery and FVIII levels were significantly higher in the liraglutide group 2 h post-surgery., Conclusion: Although the human GLP-1 analogue liraglutide moderately reduced post-operative blood glucose levels in non-diabetic and prediabetic obese patients undergoing elective hip surgery, no changes were observed with respect to coagulation activation.

Background & Aims: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism., Methods: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured., Results: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters., Conclusions: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566)., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Low-dose aspirin seems to offer no benefit in the primary prevention of cardiovascular disease in type 2 diabetes mellitus (DM2). The anti-platelet effect may be diminished by poor glycemic control or inadequate dosing of aspirin., Objectives: To study the effects of both glycemic control and increasing aspirin dose on platelet response to aspirin in DM2 patients and matched controls., Patients/methods: Platelet effects of increasing doses of aspirin (30, 100 and 300 mg daily) were prospectively assessed in 94 DM2 patients and 25 matched controls by measuring thromboxane levels in urine (11-dhTxB2) and platelet aggregation using VerifyNow(®) and light transmission aggregometry (LTA). DM2 patients were stratified for glycemic control (hemoglobin-A1c [HbA1c] ≤ 53, 53-69, ≥ 69 mmol mol(-1))., Results: At baseline, median 11-dhTxB2 excretion was higher in the poorly controlled patients (77 ng mmol(-1)), and the moderately controlled (84 ng mmol(-1)) compared with the well-controlled patients (64 ng mmol(-1)) and controls (53 ng mmol(-1)), P < 0.01. Next, 30 mg of aspirin reduced 11-dhTxB2 excretion to 31, 29 and 24 ng mmol(-1) in the poorly, moderately and well-controlled patients, respectively, and to 19 ng mmol(-1) in controls, P < 0.001. VerifyNow(®) and LTA were also incompletely suppressed in DM2 patients using 30 mg of aspirin, but 100 mg resulted in similar platelet suppression in all groups, with no additional effect of 300 mg., Conclusions: DM2 patients with inadequate glycemic control (HbA1c > 53 mmol mol(-1)) have higher baseline platelet activity and incomplete suppression of platelet activity with 30 mg of aspirin. However, 100 mg of aspirin leads to optimal inhibition irrespective of glycemic control, and 300 mg does not further improve platelet suppression., (© 2012 International Society on Thrombosis and Haemostasis.)

Due to the diabetes pandemic the number of diabetic patients admitted to the intensive care unit (ICU) increases. Diabetic patients admitted to the ICU are more vulnerable for developing complications as compared to non-diabetic patients, but this does not directly translate into higher mortality rates. However, mortality might differ per admission diagnosis. Hyperglycaemia is common in diabetic as well as non-diabetic critically ill patients, but probably chronic hyperglycaemia is pathophysiologically different from acute hyperglycaemia. As opposed to non-diabetic patients, there is discussion about the association between hyperglycaemia and mortality in diabetic patients. They do not seem to benefit from strict glycaemic control and also glucose variability appears less harmful, although clinical trials in diabetic populations have not been performed yet. Diabetes is a risk factor for hypoglycaemia and evidence suggests that even near-normal glucose levels are associated with worse outcome. Taking this together, it is suggested to strive for moderate targets when treating hyperglycaemia in critically ill diabetic patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaired fibrinolysis. Hyperglycemia plays an important role in the development of these hemostatic abnormalities, as is illustrated by the association with glycemic control and the improvement upon treatment of hyperglycemia. Interestingly, stress induced hyperglycemia, which is often transient, has also been associated with poor outcome in thrombotic disease. Similar laboratory findings suggest a common effect of acute vs. chronic hyperglycemia on the coagulation system. Many mechanisms have been proposed to explain this prothrombotic shift in hyperglycemia, such as a direct effect on gene transcription of coagulation factors caused by hyperglycemia-induced oxidative stress, loss of the endothelial glycocalyx layer, which harbours coagulation factors, and direct glycation of coagulation factors, altering their activity. In addition, both chronic and acute hyperglycemia are often accompanied by hyperinsulinemia, which has been shown to have prothrombotic effects as well. In conclusion, the laboratory evidence of the effects of both chronic and acute hyperglycemia suggests a prothrombotic shift. Additionally, hyperglycemia is associated with poor clinical outcome of thrombotic events. Whether intensive treatment of hyperglycemia can prevent hypercoagulability and improve clinical outcome remains to be investigated., (© 2010 International Society on Thrombosis and Haemostasis.)

Background: Patients with (undiagnosed) diabetes mellitus, impaired glucose tolerance or stress-induced hyperglycemia may be at greater risk for venous thrombosis and present with relative hyperglycemia during the thrombotic event., Objectives: To assess whether venous thrombosis is associated with hyperglycemia at diagnosis., Patients/methods: We performed a case-control study, derived from a cohort of consecutive patients referred for suspected deep vein thrombosis. Cases were patients with confirmed symptomatic venous thrombosis of the lower extremity. Controls were randomly selected in a 1 : 2 ratio from individuals in whom this diagnosis was excluded. We measured plasma glucose levels upon presentation to the hospital., Results: In total, 188 patients with thrombosis and 370 controls were studied. The glucose cut-off levels for the first to fourth quartiles were as follows: first quartile, < 5.3 mmol L(-1); second quartile, 5.3-5.7 mmol L(-1); third quartile, 5.7-6.6 mmol L(-1); and fourth quartile, >or= 6.6 mmol L(-1). When adjusted for body mass index, a known history of diabetes mellitus, age, sex, ethnicity and whether known risk factors for deep vein thrombosis were present, the odds ratios for deep vein thrombosis in the second, third and fourth quartiles of glucose levels as compared with the first quartile were 1.59 [95% confidence interval (CI) 0.89-2.85], 2.04 (95% CI 1.15-3.62) and 2.21 (95% CI 1.20-4.05), respectively; P for trend = 0.001., Conclusions: Increased glucose levels measured at presentation were associated with venous thrombosis. Experimental evidence supports a potential causal role for hyperglycemia in this process. As this is the first report on the association between (stress) hyperglycemia and venous thrombosis, confirmation in other studies is required.

Objective: To identify and compare patient and professional perspectives on what enables employees with diabetes mellitus (DM) to maintain their position in the workplace. To provide information on how professionals can help DM patients cope at work., Methods: Qualitative study using concept-mapping sessions involving 23 employees with DM and 22 health professionals (GP's, occupational physicians and specialists). All of the health professionals were experts in the field of diabetes care., Results: Patients and professionals identified five common clusters of statements on what diabetics need to enable them to cope at work: the ability to accept and cope with DM, supportive health professionals, a supportive work environment, work adaptations and good information. Patients emphasized the importance of emotional acceptance of DM and communication with colleagues, while the professionals emphasized the patient's capacity for self-care., Conclusion: The content of patient and professional perspectives on what is needed to prevent work-related problems for DM patients differed slightly. Patients rely on direct experiences in their own environment, professionals on medical knowledge accumulated in groups of patients., Practice Implications: Both perspectives were used to suggest a topic list for health professionals, which may help identify and address the occupational problems experienced by DM patients.

Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a potential confounder., Methods: An observational study was performed in 215 subjects with type 1 diabetes treated with multiple insulin injection therapy. Atherosclerosis was assessed by measurement of carotid intima-media thickness (CIMT)., Results: The cumulative dose of regular insulin showed a positive and significant relation with CIMT: increase of 21 microm in CIMT per S.D. of insulin use (95% CI: 8-35 adjusted for gender and age), which remained unchanged after adjustment for duration of diabetes, HbA1c, BMI, pulse pressure, physical activity and carotid lumen diameter. A similar relation was found for intermediate-acting insulin: 15.5 microm per S.D. (2-29), which was no longer present after further adjustment., Conclusions: These findings provide evidence that a high cumulative dose of regular insulin is a risk factor for atherosclerosis.

Objective: To evaluate whether hyperglycaemia in the first 48 h after infrainguinal vascular surgery is a risk factor for post-operative infection, independent from factors associated with insulin resistance and surgical stress., Design: Retrospective cohort study., Patients and Methods: Patients who underwent infrainguinal vascular surgery in our hospital between March 1998 and March 2003 were included. Glucose values until 48 h after surgery were retrieved from laboratory reports. Post-operative infections, treated with antibiotics, during hospital stay were scored until 30 days after surgery. Data were analysed with univariate and multivariate logistic regression analyses., Results: At least one post-operative glucose value was retrieved for 211/275 (77%) patients. The incidence of post-operative infections was 84/275 (31%). When corrected for factors associated with insulin resistance and surgical stress, post-operative glucose levels were found to be an independent risk factor for post-operative infections (odds ratio top quartile versus lowest quartile: 5.1; 95% confidence interval: 1.6-17.1; P=0.007)., Conclusion: Post-operative glucose levels appear to be an independent risk factor for infections after infrainguinal vascular surgery. This finding requires confirmation in a prospective study.

To establish the effects of a meal on portal venous flow and the prognostic value of this parameter, 46 patients with chronic liver disease and 28 healthy subjects were examined with duplex Doppler before and after a meal. The measurements were completed in 40 patients and 21 healthy subjects. Postprandial portal venous diameter, blood velocity and quantitative flow were measured for 60 min. Mean baseline values were: 11.4 mm versus 10.2 mm (p = 0.019), 10.8 cm.s-1 versus 13.4 cm.s-1 (p = 0.015) and 668 ml.min-1 versus 646 ml.min-1 (p = 0.7) respectively. Spleen size was 15.0 cm versus 10.6 cm (p = 0.0001) respectively. Postprandial diameter, velocity and flow increased significantly in patients and controls (p = 0.0001 for all). Mean postprandial flow could best be described by a polynomial equation with a parabolic curve. Patients' curves were more blunted than controls', with significantly different regression constants (p = 0.025 and p = 0.029). All subjects were followed up for survival and variceal haemorrhage. The mean follow-up time was 47 months. Early maximum postprandial velocity (p = 0.041) and large spleen size (p = 0.002) were significantly related to an unfavourable prognosis for survival. Early maximum velocity was also related to increased variceal haemorrhage. This study shows that postprandial portal venous flow is blunted in patients with chronic liver disease. Postprandial portal venous flow may have prognostic significance.

We investigated the variability of quantitative duplex Doppler measurements of portal flow. Measurements were validated in vitro using a flow phantom. The measured flow Q (ml/min), is related to the actual phantom output P (ml/min) according to the following formula: Q = 1.08 (P + 44) (r = 0.998). To estimate inter- and intra-observer variance, 38 subjects without portal hypertension were examined in two groups. Two observers examined the first group of subjects (n = 19), from a routine daily ultrasound schedule. Significant differences were found in mean +/- S.D. portal flow (692 +/- 182 ml/min vs. 613 +/- 185 ml/min, p = 0.04) and mean +/- S.D. velocity (15.3 +/- 3.9 cm/s vs. 13.2 +/- 2.6 cm/s, p = 0.01). The combined inter- and intra-observer coefficient of variation (S.D.) was 24% (158 ml/min), 9% (0.92 mm) and 24% (3.4 cm/s) for portal flow, diameter and velocity respectively. Non-systematic components of variance were the largest. Patient characteristics, age, sex, height, weight and body surface area did not influence measurement variations. In the second group of healthy volunteers (n = 19), where variance in measurements over 3 consecutive days was comparable to the combined variance in the first group, the non-systematic variance component was also the largest. We conclude that quantitative duplex Doppler measurements of portal venous flow are mainly subject to non-systematic variability. A coefficient of variation of 24% can be expected in diagnostic measurements in a single patient. Examination by a single observer is advisable. The value of this technique lies in the analysis of pathophysiological mechanisms in portal flow changes in large groups of subjects.