Glycemic Outcomes in Adults With T1D Are Impacted More by Continuous Glucose Monitoring Than by Insulin Delivery Method: 3 Years of Follow-Up From the COMISAIR Study.

OBJECTIVE: This study assessed the clinical impact of four treatment strategies in adults with type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections (rtCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (rtCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+MDI), and SMBG with CSII (SMBG+CSII). RESEARCH DESIGN AND METHODS: This 3-year, nonrandomized, prospective, real-world, clinical trial followed 94 participants with T1D (rtCGM+MDI, n = 22; rtCGM+CSII, n = 26; SMBG+MDI, n = 21; SMBG+CSII, n = 25). The main end points were changes in A1C, time in range (70-180 mg/dL [3.9-10 mmol/L]), time below range (<70 mg/dL [<3.9 mmol/L]), glycemic variability, and incidence of hypoglycemia. RESULTS: At 3 years, the rtCGM groups (rtCGM+MDI and rtCGM+CSII) had significantly lower A1C (7.0% [53 mmol/mol], P = 0.0002, and 6.9% [52 mmol/mol], P < 0.0001, respectively), compared with the SMBG+CSII and SMBG+MDI groups (7.7% [61 mmol/mol], P = 0.3574, and 8.0% [64 mmol/mol], P = 1.000, respectively), with no significant difference between the rtCGM groups. Significant improvements in percentage of time in range were observed in the rtCGM subgroups (rtCGM+MDI, 48.7-69.0%, P < 0.0001; and rtCGM+CSII, 50.9-72.3%, P < 0.0001) and in the SMBG+CSII group (50.6-57.8%, P = 0.0114). Significant reductions in time below range were found only in the rtCGM subgroups (rtCGM+MDI, 9.4-5.5%, P = 0.0387; and rtCGM+CSII, 9.0-5.3%, P = 0.0235). Seven severe hypoglycemia episodes occurred: SMBG groups, n = 5; sensor-augmented insulin regimen groups, n = 2. CONCLUSIONS: rtCGM was superior to SMBG in reducing A1C, hypoglycemia, and other end points in individuals with T1D regardless of their insulin delivery method. rtCGM+MDI can be considered an equivalent but lower-cost alternative to sensor-augmented insulin pump therapy and superior to treatment with SMBG+MDI or SMBG+CSII therapy.

Diabetes, Cardiovascular Disorders and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Body Burden in Czech Patients 50 Years After the Intoxication.

The correlation between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication and the parameters of metabolic impairment was examined in the last eight male survivors of 80 workers exposed to TCDD during the production of herbicides in a chemical factory in 1965-1967. Their median TCDD blood level was 112 (46-390) pg/g lipids, and the median TCDD body deposit was 3.9 (0.8-11.7) µg. This puts these patients into the most severely intoxicated group of subjects, according to back-calculated levels of TCDD. The median TCDD blood level in eight controls was 12 pg/g (<0.10 to 22.2 pg/g). Markers of metabolic impairment - diabetes, dyslipidaemia, arterial hypertension, carotid artery plaque, skin microvascular reactivity, eye fundus hypertensive angiopathy and history of coronary heart disease - were assessed and compared to a general male population of comparable age. Measured parameters compared with a population of comparable age were as follows: prevalence of diabetes (62.5% versus 17.6%), arterial hypertension (87.5% versus 71.8%), dyslipidaemia (87.5% versus 88.8%), history of coronary heart disease (62.5% versus 26.0%) and eye fundus hypertension angiopathy (50% versus 14%). All eight patients (100% versus 43%) developed plaques in carotid arteries, six had stenosis >50% and two had a carotid intervention (stenting or endarterectomy). Total cholesterol levels decreased compared to the earlier study this patient group in 2008, most likely due to a more intensive use of lipid-lowering drugs. Several metabolic parameters were higher (diabetes as much as 3.5-fold) in the group of severely TCDD-intoxicated subjects than in a general population of comparable age. This suggests that TCDD plays a role in the development of metabolic impairment and vascular changes.

Comparison of Different Treatment Modalities for Type 1 Diabetes, Including Sensor-Augmented Insulin Regimens, in 52 Weeks of Follow-Up: A COMISAIR Study.

OBJECTIVE: To compare different treatment modalities for patients with type 1 diabetes (T1D) based on real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG) combined with multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: Sixty-five T1D patients were followed up for a year. Of these, 27 started RT-CGM as part of a sensor-augmented insulin regimen (SAIR); within this SAIR group, 15 subjects started sensor-augmented pump (SAP) therapy and the remaining 12 continued with MDIs (MDIs + RT-CGM). A second group of 20 patients initiated CSII without RT-CGM, while a third group of 18 subjects continued on MDIs and SMBG. The main endpoints were reduction of HbA1c, glycemic variability (GV), and incidence of hypoglycemia. RESULTS: After a year, the baseline mean HbA1c in the SAIR group (8.3%) decreased to 7.1% (P < 0.0001); both SAIR subgroups, SAP and MDIs + RT-CGM, showed comparable improvement. The CSII group also had reduced HbA1c (8.4% ± 0.9% vs. 7.9% ± 0.7%; P < 0.05). Both SAIRs were superior to MDIs (P = 0.002) and CSII (P = 0.0032). GV was also lowered, both in the SAIR (P < 0.0001) and CSII (P < 0.05) groups. Reduced incidence of hypoglycemia was observed only with SAIR (8% ± 4% vs. 6% ± 3%; P < 0.01). CONCLUSION: Both SAIRs, SAP and MDIs + RT-CGM, provided significant and comparable decrease of HbA1c with concurrent reduction of hypoglycemia. This improvement was greater than that seen with CSII. The combination of RT-CGM and MDIs can be a suitable alternative to SAP for some patients.

[Insulin application techniques in adult patients with diabetes]. / Aplikacní technika inzulinu u dospelých pacientu s diabetem.

UNLABELLED: Treatment of diabetes mellitus with insulin is associated with a large number of subcutaneous injections. Incorrect insulin application technique can lead to complications both local (lipohypertrophy, scars) and systemic (high variability of insulin absorption and action, unexpected hypoglycemia or hyperglycemia, suboptimal overall glucose control). Regarding insulin application, we need to pay particular attention to the risk of intramuscular application and consequent less expectable insulin effect. The risk of accidental intramuscular administration of insulin is reduced when shorter 4 mm insulin pen needles are used. Repeated application of insulin in the same locations may cause changes in the subcutaneous tissue (lipohypertrophy, inflammation). Application sites should be examined during routine checks at diabetes clinics. Patients should also be repeatedly advised to rotate the injection sites as a prevention of lipohypertrophy formation and not to inject any more injections into pathologically changed subcutaneous tissue. At the same time, patients should be advised that their total insulin dose may be decreased, and that they are temporarily at higher risk of hypoglycemia, if they switch injecting from lipohypertrophy changed tissue into healthy tissue. KEY WORDS: glucose variability - insulin application - lipohypertrophy - needles.

Oxidative stress markers are elevated in exhaled breath condensate of workers exposed to nanoparticles during iron oxide pigment production.

Markers of oxidative stress and inflammation were analysed in the exhaled breath condensate (EBC) and urine samples of 14 workers (mean age 43 ± 7 years) exposed to iron oxide aerosol for an average of 10 ± 4 years and 14 controls (mean age 39 ± 4 years) by liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) after solid-phase extraction. Aerosol exposure in the workplace was measured by particle size spectrometers, a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS), and by aerosol concentration monitors, P-TRAK and DustTRAK DRX. Total aerosol concentrations in workplace locations varied greatly in both time and space. The median mass concentration was 0.083 mg m(-3) (IQR 0.063-0.133 mg m(-3)) and the median particle concentration was 66 800 particles cm(-3) (IQR 16,900-86,900 particles cm(-3)). In addition, more than 80% of particles were smaller than 100 nm in diameter. Markers of oxidative stress, malondialdehyde (MDA), 4-hydroxy-trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2α (8-isoprostane) and aldehydes C6-C12, in addition to markers of nucleic acid oxidation, including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU), and of proteins, such as o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr) were analysed in EBC and urine by LC-ESI-MS/MS. Almost all markers of lipid, nucleic acid and protein oxidation were elevated in the EBC of workers comparing with control subjects. Elevated markers were MDA, HNE, HHE, C6-C10, 8-isoprostane, 8-OHdG, 8-OHG, 5-OHMeU, 3-ClTyr, 3-NOTyr, o-Tyr (all p < 0.001), and C11 (p < 0.05). Only aldehyde C12 and the pH of samples did not differ between groups. Markers in urine were not elevated. These findings suggest the adverse effects of nano iron oxide aerosol exposure and support the utility of oxidative stress biomarkers in EBC. The analysis of urine oxidative stress biomarkers does not support the presence of systemic oxidative stress in iron oxide pigment production workers.