People with type 1 diabetes and impaired awareness of hypoglycaemia have a delayed reaction to performing a glucose scan during hypoglycaemia: a prospective observational study.

AIMS: Considering that people with type 1 diabetes and impaired awareness of hypoglycaemia (IAH) have a delayed perception of hypoglycaemia, the question arises whether they perform scans later in case of hypoglycaemia than people without IAH. We assessed whether time to performing a scan after reaching hypoglycaemia while using a flash glucose monitoring (flash GM) system is different in people with IAH compared with people without IAH. METHODS: Ninety-two people with type 1 diabetes [mean (± sd) age 42 ± 14 years, HbA1c 57 ± 9 mmol/mol] using a flash GM system for 3 months were included. Flash GM data were assessed for time until scan after reaching hypoglycaemia level 1 (< 3.9 mmol/l) and level 2 (< 3.0 mmol/l) and compared for type 1 diabetes with vs. without IAH via unpaired t-test/Mann-Whitney U test (P < 0.05). RESULTS: Significant differences were found only for the delay between reaching hypoglycaemia and scan between people with and without IAH for Gold score [hypoglycaemia level 1: IAH 78 (51-105) min vs. without IAH 63 (42-89) min, P = 0.03; night-time hypoglycaemia level 2: IAH 140 (107-227) min vs. without IAH 96 (41-155) min, P = 0.004] and Pedersen-Bjergaard score [hypoglycaemia level 1: IAH 76 (52-97) min vs. without IAH 54 (38-71) min, P = 0.011; night-time hypoglycaemia level 1: IAH 132 (79-209) min vs. without IAH 89 (59-143) min, P = 0.011; night-time hypoglycaemia level 2: IAH 134 (66-212) min vs. without IAH 80 (37-131) min, P = 0.002). Data are shown as median (i.q.r.). CONCLUSIONS: Time until scan after reaching hypoglycaemia might be an objective assessment tool for IAH, but needs to be investigated comprehensively in future studies.

Impact of physical exercise on sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system in people with Type 1 diabetes: a randomized crossover trial.

AIMS: To evaluate the sensor performance of the FreeStyle Libre intermittently viewed continuous glucose monitoring system using reference blood glucose levels during moderate-intensity exercise while on either full or reduced basal insulin dose in people with Type 1 diabetes. METHODS: Ten participants with Type 1 diabetes [four women, mean ± sd age 31.4 ± 9.0 years, BMI 25.5±3.8 kg/m2 , HbA1c 55±7 mmol/mol (7.2±0.6%)] exercised on a cycle ergometer for 55 min at a moderate intensity for 5 consecutive days at the clinical research facility, while receiving either their usual or a 75% basal insulin dose. After a 4-week washout period, participants performed the second exercise period having switched to the alternative basal insulin dose. During exercise, reference capillary blood glucose values were analysed using the fully enzymatic-amperometric method and compared with the interstitial glucose values obtained. Intermittently viewed continuous glucose monitoring accuracy was analysed according to median (interquartile range) absolute relative difference, and Clarke error grid and Bland-Altman analysis for overall glucose levels during exercise, stratified by glycaemic range and basal insulin dosing scheme (P<0.05). RESULTS: A total of 845 glucose values were available during exercise to evaluate intermittently viewed continuous glucose monitoring sensor performance. The median (interquartile range) absolute relative difference between the reference values and those obtained by the sensor across the glycaemic range overall was 22 (13.9-29.7)%, and was 36.3 (24.2-45.2)% during hypoglycaemia, 22.8 (14.6-30.6)% during euglycaemia and 15.4 (9-21)% during hyperglycaemia. Usual basal insulin dose was associated with a worse sensor performance during exercise compared with the reduced (75%) basal insulin dose [median (interquartile range) absolute relative difference: 23.7 (17.2-30.7)% vs 20.5 (12-28.1)%; P<0.001). CONCLUSIONS: The intermittently viewed continuous glucose monitoring sensor showed diminished accuracy during exercise. Absolute glucose readings derived from the sensor should be used cautiously and need confirmation by additional finger-prick blood glucose measurements.

Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with Type 2 diabetes.

AIMS: Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. METHODS: Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. RESULTS: Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. CONCLUSIONS: In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule.

Short communication: Effect of supplementation with Lactobacillus casei Shirota on insulin sensitivity, ß-cell function, and markers of endothelial function and inflammation in subjects with metabolic syndrome--a pilot study.

Based on animal studies, intake of probiotic bacteria was suggested to improve insulin sensitivity by reducing endotoxinemia and inflammation. The objective of this study was to determine the effects of supplementation with the probiotic strain Lactobacillus casei Shirota (LcS) over 12 wk on insulin sensitivity, ß-cell function, inflammation, and endothelial dysfunction parameters in subjects with metabolic syndrome. In a randomized-controlled study, 30 subjects with metabolic syndrome either received Lactobacillus casei Shirota 3 times daily for 12 wk or served as controls with standard medical therapy. Fasting blood samples were taken and a 75-g oral glucose tolerance test was performed to derive indices for insulin sensitivity and ß-cell function. In addition, parameters to assess endothelial function and inflammation markers were determined. Even though the insulin sensitivity index significantly improved after 3 mo of probiotic supplementation (0.058±0.021 vs. 0.038±0.025), the change was not significantly different compared with the control group. No improvements were seen in additional indices of insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity by oral glucose tolerance test, and homeostasis model assessment for insulin resistance) and ß-cell function (first and second phase insulin secretion, and homeostasis model assessment for ß-cell function). Probiotic supplementation resulted in a significant reduction in soluble vascular cell adhesion molecule-1 (sVCAM-1) level (1,614±343 vs. 1,418±265 ng/mL). No significant changes in parameters used to assess low-grade inflammation or endothelial dysfunction were observed. Intake of LcS for 12 wk in subjects with metabolic syndrome did not improve insulin sensitivity, ß-cell function, endothelial function, or inflammation markers in this trial.

Multifactorial risk factor intervention in patients with Type 2 diabetes improves arginine bioavailability ratios.

AIM: Endothelial dysfunction is defined by reduced bioavailability of nitric oxide and has been shown to be associated with cardiovascular risk. The global arginine bioavailability ratio and the arginine to ornithine ratio have recently been shown to be associated with cardiovascular outcome in patients with coronary artery disease. The aim of our study was to investigate the impact of a multifactorial risk factor intervention in subjects with Type 2 diabetes on these two potential new cardiovascular surrogate parameters. METHODS: In a single-centre and prospective study, we investigated 41 patients with Type 2 diabetes not reaching treatment targets according to current local diabetes guidelines in two out of three of the following measurements: HbA(1c) LDL cholesterol 2.6 or blood pressure. Within 3 months, therapy was intensified according to current guidelines aiming to reach the treatment targets. At baseline and 3 months, arginine, ornithine and citrulline were chromatographically determined after pre-column-derivatization followed by fluorescent detection, and arginine bioavailability ratios were calculated. RESULTS: Intensified risk factor management significantly improved the global arginine bioavailability ratio (0.33 ± 0.12 at baseline vs. 0.38 ± 0.14 after 3 months; P = 0.018). A significant improvement was only seen in patients with short diabetes duration (< 5 years), whereas in patients with longer diabetes duration improvement did not reach statistical significance. CONCLUSION: In patients with Type 2 diabetes, intensified risk factor management improves arginine bioavailability ratios. Duration of diabetes seems to be an important factor influencing the capacity of the global arginine bioavailability ratio improvement.

Differential effects of fluvastatin alone or in combination with ezetimibe on lipoprotein subfractions in patients at high risk of coronary events.

BACKGROUND: Ezetimibe, a cholesterol-absorption inhibitor, significantly lowers low-density lipoprotein cholesterol (LDL-C) when administered in addition to statin treatment. The effect of ezetimibe on the incidence and progression of vascular disease is elusive. The objective of the study was to examine the effects of fluvastatin plus ezetimibe on lipoprotein subfractions in patients with type 2 diabetes and/or coronary heart disease. MATERIALS AND METHODS: Ninety patients with LDL-C between 100 and 160 mg dL(-1) were enrolled in this prospective, randomized, single-blind, single-centre study. A total of 84 patients were treated with either fluvastatin 80 mg (n = 28) alone or in combination with ezetimibe 10 mg (n = 56) for 12 weeks to determine the effects on lipids, apolipoproteins and LDL subfractions by equilibrium density gradient ultracentrifugation. This study is registered with ClinicalTrials.gov, number NCT00814723. RESULTS: Total cholesterol, LDL-C and apolipoprotein B were significantly more reduced in the combined therapy group. High density lipoproteins increased in the fluvastatin-only group and decreased in the combined therapy group. There was a significant difference between the two groups in buoyant and intermediate, but not in dense LDL particles. CONCLUSIONS: Addition of ezetimibe to fluvastatin resulted in a further reduction of buoyant and intermediate, but not of dense LDL compared with fluvastatin alone.

The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study.

BACKGROUND/OBJECTIVES: Obesity and metabolic disorders are linked to inflammation via gut microbiota and/or gut permeability. Gut-derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. We intended to investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS. SUBJECTS/METHODS: Patients with MetS were randomized to receive 3 × 6.5 × 109 CFU L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method and by determination of diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) levels. RESULTS: Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared with controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. High-sensitive C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups. CONCLUSIONS: Gut permeability of MetS patients was increased significantly compared with healthy controls. L. casei Shirota administration in the MetS patients did not have any influence on any parameter tested possibly due to too-short study duration or underdosing of L. casei Shirota.

Non-glycemic effects of insulin therapy: a comparison between insulin aspart and regular human insulin during two consecutive meals in patients with type 2 diabetes.

OBJECTIVE: To control postprandial hyperglycemia in insulin-treated type 2 diabetic patients, prandial therapy with regular human insulin (HI) or fast acting insulin analogs is used. Postprandial hyperglycemia seems to be reduced more effectively with insulin analogs than with normal insulin, but there are no data concerning the effect on lipolysis or pancreatic insulin and proinsulin secretion of normal insulin in comparison to insulin analogs. DESIGN AND METHODS: We included 13 patients with type 2 diabetes mellitus (age 62.2±10.3 years) with preexisting insulin therapy in this crossover, prospective, open-labeled, randomized trial comparing regular HI with insulin aspart (IA) in the setting of a standardized breakfast and a standardized lunch 4 h later. Blood samples for determination of glucose, free fatty acids (FFA), triglycerides, C-peptide, and intact proinsulin were drawn during fasting and every 30 min until 4 h after the second test meal. Statistical analysis was performed with ANOVA for repeated measurements and paired Student's t-test. RESULTS: The mean increase in blood glucose was significantly lower after IA (24.18±16.33 vs 34.92±29.07 mg/dl, P=0.02) compared with HI. Both therapies reduced FFA; however, the mean reduction was significantly higher after IA than after HI (-0.47±0.16 vs -0.35±0.15 µmol/l, P<0.001). The mean increase in intact proinsulin was significantly lower after IA than after HI (10.53±5 vs 15.20±6.83 pmol/l, P<0.001). No differences were observed in the C-peptide levels between the two groups. CONCLUSION: In the setting of two consecutive meals, IA reduces lipolysis and proinsulin secretion more effectively than HI.

[Cerebrotendinous xanthomatosis. Hereditary lipid storage disease leading to bilateral swelling of Achilles tendon]. / Zerebrotendinöse Xanthomatose. Bilaterale Achillessehnenschwellung durch angeborene Stoffwechselstörung.

Cerebrotendinous xanthomatosis is a rare hereditary lipid storage disease characterised by deposits of cholestanol. In a female patient with bilateral swelling of the Achilles tendon who underwent biopsy, cerebrotendinous xanthomatosis was confirmed by combining disease patterns. She suffered from ataxia, depression, epilepsy, reduced intelligence, bilateral cataracts, gallstones, and atherosclerosis. Concentration of serum cholestanol was 10 times higher than normal. As causal therapy, ursodeoxycholic acid and statin drugs were prescribed to halt progression.