Begoña Manuel-y-Keenoy

Intensive Insulin Therapy in the Intensive Care Unit Assessment by continuous glucose monitoring

OBJECTIVE—Hyperglycemia occurs in most critically ill patients. Using continuous glucose monitoring (CGM), we investigated whether intensive insulin therapy based on discontinuous glucose monitoring can achieve normoglycemia (80–110 mg/dl) in a medical intensive care unit (MICU). RESEARCH DESIGN AND METHODS—Fifty adults (men/women 31/19, age 62 ± 16 years, nondiabetic/diabetic 30/20, intravenous/subcutaneous insulin 22/28, and Acute Physiology and Chronic Health Evaluation II score 22 ± 7) were prospectively recruited. Forty-eight–hour CGM was performed using a subcutaneous glucose sensor (GlucoDay) and compared with arterial glycemia. Main outcome measures were percent of time in normoglycemia and accuracy/applicability of CGM. RESULTS—During 48-h CGM, glycemia reached target (80–110 mg/dl) in only 22 ± 18%, was >140 mg/dl in 39 ± 27%, and was <60 mg/dl in 5 ± 10% of the time. Patients on subcutaneous versus intravenous insulin had more glycemia readings >110 mg/dl (P = 0.016). Glycemia was higher in diabetic patients (170 ± 77 vs. 129 ± 35 mg/dl, P = 0.013). BMI was an independent determinant for bad glycemic control (β = 0.73, P < 0.0001). Diabetic state (β = 0.47, P < 0.0001), septic shock (β = 0.22, P = 0.045), sequential organ failure assessment score (β = 0.40, P = 0.001), and use of corticoids (β = 0.28, P = 0.014) and inotropics (β = −0.24, P = 0.035) were independent determinants of insulin dose. GlucoDay values and arterial glycemia correlated well (r = 0.85, P < 0.0001, n = 555 after six-point calibration), with 97% of data falling in regions A and B of error grid analysis. There were no adverse events using GlucoDay. CONCLUSIONS—GlucoDay, a well-tolerated 48-h CGM system, revealed that normoglycemia was only achieved 22% of the time in MICU patients. Further studies should investigate whether application of CGM to titrate insulin therapy can improve patient outcome.

Oxidative stress status in patients with diabetes mellitus: relationship to diet

Objective: To investigate the relationship between dietary intakes and in vivo oxidative stress (OS) status in diabetic patients.Design: Case–control study.Setting: Outpatient-Clinic and Laboratory Endocrinology, University Antwerp.Subjects and methods: A total of 30 patients (24 type 1 diabetes mellitus (T1DM)/6 type 2 diabetes mellitus (T2DM) were asked to complete a 2 weekdays+1weekend day food consumption questionnaire during the week preceding their yearly diabetes control consultation, when samples were collected for the assay of oxidative stress (OS) (blood levels of antioxidants, peroxides, malondialdehyde (MDA) and minerals). Blood samples were also collected from 25 age- and sex-matched healthy controls.Results: Diabetic patients had lower glutathione (5.80±1.15 vs 6.75±1.03 μmol/g Hb in the controls, P=0.002) and higher MDA (0.687±0.212 vs 0.545±0.101 μmol/l, P=0.002). Although the group average intakes were within the Belgian RDA, intakes of fat >35% energy, fibre <15 g/1000 kcal, fruit <2 portions and vitamin E <10 mg/day were seen in more than 20 patients. Blood antioxidants did not correlate with intakes of energy, fat, protein or fibres or of their respective antioxidant. Vitamins A and E correlated with serum lipids (r=0.58, P <0.0005 between serum α-tocopherol and cholesterol). Blood peroxide levels were only related to intakes of saturated fat and cholesterol (P<0.05). In diabetic subjects but not in controls (P<0.05) MDA was related to glutathione and uric acid.Conclusions: In diabetic patients, blood levels of antioxidants are not related to their dietary intakes but to serum lipids. Levels of oxidative damage products are only related to intakes of saturated fats and cholesterol and to levels of endogenous antioxidants.

Transferrin modifications and lipid peroxidation: implications in diabetes mellitus.

Free iron is capable of stimulating the production of free radicals which cause oxidative damage such as lipid peroxidation. One of the most important mechanisms of antioxidant defense is thus the sequestration of iron in a redox-inactive form by transferrin. In diabetes mellitus, increased oxidative stress and lipid peroxidation contribute to chronic complications but it is not known if this is related to abnormalities in transferrin function. In this study we investigated the role of transferrin concentration and glycation. The antioxidant capacity of apotransferrin to inhibit lipid peroxidation by iron-binding decreased in a concentration-dependent manner from 89% at <formula>≥2 mg/ml</formula> to 42% at 0.5 mg/ml. Pre-incubation of apotransferrin with glucose for 14 days resulted in a concentration-dependent increase of glycation: 1, 5 and 13 μmol fructosamine/g transferrin at 0, 5.6 and 33.3 mmol/l glucose respectively, p<0.001. This was accompanied by a decrease in the iron-binding antioxidant capacity of apotransferrin. In contrast, transferrin glycation by up to 33.3 mmol/l glucose did not affect chemiluminescence-quenching antioxidant capacity, which is iron-independent. Colorimetric evaluation of total iron binding capacity in the presence of an excess of iron (iron/transferrin molar ratio=2.4) also decreased from 0.726 to 0.696 and 0.585 mg/g transferrin after 0, 5.6 and 33.3 mmol/l glucose, respectively, p<0.01. In conclusion, these results suggest that lower transferrin concentration and its glycation can, by enhancing the pro-oxidant effects of iron, contribute to the increased lipid peroxidation observed in diabetes.

Impact of diabetes mellitus on the relationships between iron-, inflammatory- and oxidative stress status

Diabetes is an inflammatory condition associated with iron abnormalities and increased oxidative damage. We aimed to investigate how diabetes affects the interrelationships between these pathogenic mechanisms.

Ferritin levels and risk of metabolic syndrome: meta-analysis of observational studies

BackgroundElevated ferritin levels have been associated with single cardiovascular risk factors but the relationship to the presence of metabolic syndrome is inconclusive.The aim of this systematic review and meta-analysis of published observational studies was to estimate the association between serum ferritin levels and metabolic syndrome in adults.MethodsThe Pubmed, SCOPUS and the Cochrane Library databases were searched for epidemiological studies that assessed the association between ferritin levels and metabolic syndrome and were published before September 2013. There were no language restrictions. Two investigators independently selected eligible studies. Measures of association were pooled by using an inverse-variance weighted random-effects model. The heterogeneity among studies was examined using the I2 index. Publication bias was evaluated using the funnel plot.ResultsTwelve cross-sectional, one case–control and two prospective studies met our inclusion criteria including data from a total of 56,053 participants. The pooled odds ratio (OR) for the metabolic syndrome comparing the highest and lowest category of ferritin levels was 1.73 (95% CI: 1.54, 1.95; I2 = 75,4%). Subgroup analyses indicate that pooled OR was 1.92 (95% CI: 1.61, 2.30; I2 = 78%) for studies adjusting for C-reactive protein (CRP), and 1.52 (95% CI:1. 36, 1.69; I2 = 41%) for studies that did not adjust for CRP (P = 0.044). This finding was remarkably robust in the sensitivity analysis. We did not find publication bias.ConclusionsThe meta-analysis suggests that increased ferritin levels are independently and positively associated with the presence of the metabolic syndrome with an odds ratio higher than 1.73.

Minimally-Invasive and Non-Invasive Continuous Glucose Monitoring Systems: Indications, Advantages, Limitations and Clinical Aspects

Accurate and reliable devices sensing glucose on a (near)-continuous basis may facilitate specific therapeutic adjustments that need to be made to avoid hypo- and hyperglycaemic excursions, thereby improving metabolic control. Current continuous glucose monitoring (CGM) systems indicate the glucose level, the direction and magnitude of change of glucose levels, and can be used to assess glycaemic variability. In addition, real-time CGM sensors can serve as a tool to predict impending glucose excursions, thereby providing alarm signals of hypo- and hyperglycaemic values warning the patient to take preventative actions. Quality of life may also improve by using CGM via reducing the fear of hypoglycaemia. Particularly patients with brittle diabetes, hypoglycaemia unawareness, gastroparesis, pregnant women, or pump users, who are motivated to participate in their diabetes care and are technologically adept, may benefit from CGM. However, to successfully implement CGM in daily practice, these devices must be accurate and reliable, and one must be aware of the limitations of current CGM systems, that originate from physiological and technical aspects. Whether CGM succeeds in improving metabolic control, reducing hypoglycaemic episodes, and improving quality of life in the majority of patients remains to be proven. Should this be the case, real-time CGM may reduce chronic diabetic complications, and avoid hospitalisations, thereby reducing health care costs. In this article we will review indications, advantages, limitations, clinical and technical aspects of current minimally-invasive and non-invasive CGM sensors.

Effects of intravenous supplementation with α-tocopherol in patients receiving total parenteral nutrition containing medium- and long-chain triglycerides

Objective: To compare the effects of a lipid emulsion containing medium-chain triglycerides (MCT) and supplemented with α-tocopherol to a conventional long-chain triglyceride (LCT) emulsion.Design: Randomised double blind study.Setting: Department of Internal Medicine, Antwerp University Hospital.Subjects and interventions: Twenty-four patients with an indication for total parenteral nutrition for a minimum of 10 days were randomly assigned to two groups: group E received as lipid source MCT/LCT (50/50) suplemented with 100 mg dl-α-tocopherol/day and group C received LCT. Blood samples were analysed at inclusion, after 4–6 and after 9–11 days.Results: In group E, serum α-tocopherol doubled from 11.4±6.9 at inclusion to 20.9±7.9 and to 23.8±8.8 µg/ml after 4 and 9 days, respectively, but did not change in group C (P=0.008). Production of thiobarbituric acid-reacting substances (TBARS) after 120 min incubation with copper decreased from 66±34 at inclusion to 29±25 nmol MDA/mg LDL and VLDL-cholesterol after 4 and to 42±17 after 9 days (P=0.022 when compared to group C, which underwent no significant changes). Velocity of production of fluorescent products decreased in group E but not in group C (P=0.026).Conclusions: Supplementation of TPN containing MCT/LCT with 100 mg dl-α-tocopherol/day leads to a doubling in serum α-tocopherol and to a decrease in the susceptibility of LDL and VLDL to peroxidation in vitro.Sponsorship: This study was partly financed by B Braun Medical NVSA, Diegem, Belgium.

Glucose Control and Use of Continuous Glucose Monitoring in the Intensive Care Unit: A Critical Review

Stress hyperglycemia recently became a major therapeutic target in the Intensive Care Unit (ICU) since it occurs in most critically ill patients and is associated with adverse outcome, including increased mortality. Intensive insulin therapy to achieve normoglycemia may reduce mortality, morbidity and the length of ICU and in-hospital stay. However, obtaining normoglycemia requires extensive efforts from the medical staff, including frequent glucose monitoring and adjustment of insulin dose. Current insulin titration is based upon discrete glucose measurements, which may miss fast changes in glycemia and which does not give a full picture of overall glycemic control. Recent evidence suggests that continuous monitoring of glucose levels may help to signal glycemic excursions and eventually to optimize insulin titration in the ICU. In this review we will summarise monitoring and treatment strategies to achieve normoglycemia in the ICU, with special emphasis on the possible advantages of continuous glucose monitoring.

Does vitamin C supplementation influence the levels of circulating oxidized LDL, sICAM-1, sVCAM-1 and vWF-antigen in healthy male smokers?

Objective: To examine the effects of vitamin C supplementation on the concentration of oxidation markers, in particular, circulating oxidized LDL (OxLDL) and on endothelial activation markers.Design: Randomized double-blind, placebo-controlled crossover trial.Setting: Belgian population of the city of Leuven.Subjects: A total of 34 healthy male smokers aged 26–73 y.Intervention: Smokers were randomly assigned to receive either vitamin C (250 mg twice daily) or placebo capsules, each to be taken for 4 weeks. After a 1-week washout period, participants then crossed over to the alternative capsules for further 4 weeks.Mean outcome measures: Markers of oxidation (bilirubin, uric acid, α-tocopherol, retinol, malondialdehyde, circulating Oxidized LDL (OxLDL)) and markers of endothelial activation (sICAM-1, sVCAM-1, vWF-antigen) were analysed.Results: Plasma ascorbate concentrations significantly increased from 46.6±17.6 to 70.1±21.2 μmol/l after a 4-week treatment with 500 mg vitamin C per day. The other plasma antioxidants concentrations, including bilirubin, uric acid, α-tocopherol and retinol, were similar in both treatment periods. Vitamin C did not change plasma malondialdehyde and circulating OxLDL compared with placebo (vitamin C 0.73±0.25 mg/dl OxLDL; placebo 0.72±0.21 mg/dl OxLDL). After vitamin C supplementation, neither sICAM-1 and sVCAM-1 levels nor the concentration of vWF-antigen significantly differed from placebo condition.Conclusions: Oral supplementation of vitamin C is not associated with changes in markers of oxidation or endothelial activation in healthy male smokers.Sponsorship: The Unilever Chair in Nutritional Epidemiology, University of Leuven, Belgium.

Postprandial glucose monitoring in type 1 diabetes mellitus: use of a continuous subcutaneous monitoring device

Pre‐prandial glucose gives insufficient information on glycemic excursions throughout the day. We aimed to test a continuous subcutaneous glucose‐monitoring device (GlucoDay®) to describe postprandial glucose changes.