Comparison of Control-IQ and open-source AndroidAPS automated insulin delivery systems in adults with type 1 diabetes: The CODIAC study.

AIM: To compare open-source AndroidAPS (AAPS) and commercially available Control-IQ (CIQ) automated insulin delivery (AID) systems in a prospective, open-label, single-arm clinical trial. METHODS: Adults with type 1 diabetes who had been using AAPS by their own decision entered the first 3-month AAPS phase then were switched to CIQ for 3 months. The results of this treatment were compared with those after the 3-month AAPS phase. The primary endpoint was the change in time in range (% TIR; 70-80 mg/dL). RESULTS: Twenty-five people with diabetes (mean age 34.32 ± 11.07 years; HbA1c 6.4% ± 3%) participated in this study. CIQ was comparable with AAPS in achieving TIR (85.72% ± 7.64% vs. 84.24% ± 8.46%; P = .12). Similarly, there were no differences in percentage time above range (> 180 and > 250 mg/dL), mean sensor glucose (130.3 ± 13.9 vs. 128.3 ± 16.9 mg/dL; P = .21) or HbA1c (6.3% ± 2.1% vs. 6.4% ± 3.1%; P = .59). Percentage time below range (< 70 and < 54 mg/dL) was significantly lower using CIQ than AAPS. Even although participants were mostly satisfied with CIQ (63.6% mostly agreed, 9.1% strongly agreed), they did not plan to switch to CIQ. CONCLUSIONS: The CODIAC study is the first prospective study investigating the switch between open-source and commercially available AID systems. CIQ and AAPS were comparable in achieving TIR. However, hypoglycaemia was significantly lower with CIQ.

Lower Glycated Hemoglobin with Real-Time Continuous Glucose Monitoring Than with Intermittently Scanned Continuous Glucose Monitoring After 1 Year: The CORRIDA LIFE Study.

Background: The aim was to compare the efficacy of real-time continuous glucose monitoring (rtCGM) and intermittently scanned continuous glucose monitoring (isCGM) focusing on glycated hemoglobin (HbA1c) as the primary endpoint. Methods: The CORRIDA LIFE was a 12-month, real-world, nonrandomized study that is part of the CORRIDA clinical trials program. The study compared rtCGM (Dexcom G5 or G6) and isCGM (FreeStyle Libre 14-Day; Abbott) in adults with type 1 diabetes (T1D). Only patients on multiple daily insulin injections or continuous subcutaneous insulin infusion with no automatic functions were included in this study. Primary outcome was the difference in HbA1c between study groups at 12 months. Results: One hundred ninety-one adults with T1D (mean age 40 ± 13 years, HbA1c 8.1% ± 3.4% [65 ± 14 mmol/mol]) participated in this study; 81 patients initiated rtCGM and 110 initiated isCGM. After 12-months, HbA1c was significantly lower with rtCGM versus isCGM (7.1% ± 3.1% [54.1 ± 10.1 mmol/mol] vs. 7.7% ± 3.3% [61.2 ± 12.2 mmol/mol]), P = 0.0001. The percentage of time in hypoglycemia (<70 mg/dL [<3.9 mmol/L]) was lower among rtCGM vs. isCGM participants [4.3% ± 2.8% vs. 6.4% ± 5.3%], P = 0.003). Patients with rtCGM spent less time in clinically significant hypoglycemia (<54 mg/dL [<3.0 mmol/L]) (0.9% ± 1.0% vs. 2.3% ± 2.5%, P < 0.0001) and more time in target range (70-180 mg/dL [3.9-10 mmol/L]) than isCGM users (67.5% ± 14.8% vs. 57.8% ± 17.0%), P = 0.0002. Conclusions: rtCGM was superior to isCGM in HbA1c, hypoglycemia, and other glycemic outcomes. Our findings provide guidance to clinicians when discussing monitoring options with their patients. The study was registered at www.clinicaltrials.gov (NCT04759495).

Skin autofluorescence corresponds to microvascular reactivity in diabetes mellitus.

Advanced glycation accelerated by chronic hyperglycaemia contributes to the development of diabetic vascular complications throughout several mechanisms. One of these mechanisms is supposed to be impaired microvascular reactivity, that precedes significant vascular changes. The aim of this study was to find an association between advanced glycation, the soluble receptor for AGEs (sRAGE), and microvascular reactivity (MVR) in diabetes. Skin autofluorescence (SAF), which reflects advanced glycation, was assessed by AGE-Reader, MVR was measured by laser Doppler fluxmetry and evaluated together with sRAGE in 43 patients with diabetes (25 Type 1 and 18 Type 2) and 26 healthy controls of comparable age. SAF was significantly higher in patients with diabetes compared to controls (2.4 ± 0.5 vs. 2.0 ± 0.5 AU; p < 0.01). Patients with diabetes with SAF > 2.3 AU presented significantly worse MVR in both post-occlusive reactive hyperaemia (PORH) on the finger and forearm, and thermal hyperaemia (TH), compared to patients with SAF < 2.3 AU. SAF was age dependent in both diabetes (r = 0.41, p < 0.01) and controls (r = 0.45, p < 0.05). There was no association between SAF and diabetes control expressed by glycated haemoglobin. A significant relationship was observed between SAF and sRAGE in diabetes (r = 0.56, p < 0.001), but not in controls. A significant inverse association was found between SAF and MVR on the forearm in diabetes (PORH: r = -0.42, p < 0.01; TH: r = -0.46, p < 0.005). Both advanced glycation expressed by higher SAF or sRAGE and impaired MVR are involved in the pathogenesis of vascular complications in diabetes, and we confirm a strong interplay of these processes in this scenario.

Diabetes management in hospital.

Patients with diabetes represent around 25 % of hospitalized persons. Treatment of diabetes patient is more complicated. Modification or initiation of antidiabetic treatment is often a significant problem during hospitalization on standard medical ward. The aim of this article is to present basic recommendations for in-patient diabetes treatment.

Real-time CGM Is Superior to Flash Glucose Monitoring for Glucose Control in Type 1 Diabetes: The CORRIDA Randomized Controlled Trial.

OBJECTIVE: The aim of this trial was to compare the efficacy of real-time and intermittently scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control. RESEARCH DESIGN AND METHODS: In this randomized study, adults with type 1 diabetes (T1D) and normal hypoglycemia awareness (Gold score <4) used rtCGM (Guardian Connect Mobile) or isCGM (FreeStyle Libre) during 4 days of physical activity (exercise phase) and in the subsequent 4 weeks at home (home phase). Primary end points were time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) and time in range (3.9-10.0 mmol/L [70-180 mg/dL]). The isCGM group wore an additional masked Enlite sensor (iPro2) for 6 days to check for bias between the different sensors used by the rtCGM and isCGM systems. RESULTS: Sixty adults with T1D (mean age 38 ± 13 years; A1C 62 ± 12 mmol/mol [7.8 ± 1.1%]) were randomized to rtCGM (n = 30) or isCGM (n = 30). All participants completed the study. Percentage of time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) was lower among rtCGM versus isCGM participants in the exercise phase (6.8 ± 5.5% vs. 11.4 ± 8.6%, respectively; P = 0.018) and during the home phase (5.3 ± 2.5% vs. 7.3 ± 4.4%, respectively; P = 0.035). Hypoglycemia differences were significant and most notable during the night. rtCGM participants spent more time in range (3.9-10 mmol/L [70-180 mg/dL]) than isCGM participants throughout both the exercise (78.5 ± 10.2% vs. 69.7 ± 16%, respectively; P = 0.0149) and home (75.6 ± 9.7% vs. 67.4 ± 17.8%, respectively; P = 0.0339) phases. The results were robust to the insignificant bias between rtCGM and isCGM sensors that masked CGM found in the isCGM arm. CONCLUSIONS: rtCGM was superior to isCGM in reducing hypoglycemia and improving time in range in adults with T1D with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management.

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.

Glycemic variability is higher in type 1 diabetes patients with microvascular complications irrespective of glycemic control.

BACKGROUND: Increased glycemic variability (GV) may be associated with diabetes complications. Our study assessed the relationship between microvascular complications (MVCs) and GV calculated from continuous glucose monitoring (CGM) data in type 1 diabetes patients. SUBJECTS AND METHODS: Thirty-two patients with type 1 diabetes (16 with and 16 without MVC) participated in this cross-sectional study. Vibration perception threshold (VPT), microalbuminuria, and fundoscopy were used to detect MVC. CGM data were recorded for 2 weeks and analyzed using proprietary software. Total SD (SDT), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE) were compared. RESULTS: Patients with any MVC had significantly higher GV, calculated from CGM, than patients without MVC (SDT, 4.1 ± 0.6 vs. 3.4 ± 0.8 mmol/L [P = 0.010]; CV, 0.43 ± 0.06 vs. 0.38 ± 0.08 [P = 0.032]; MAGE, 6.9 ± 1.2 vs. 5.9 ± 1.2 mmol/L [P = 0.014]) but comparable glycated hemoglobin (HbA1c) (70 ± 9 vs. 69 ± 10 mmol/mol [8.6 ± 0.8% vs. 8.5 ± 0.9%], difference not significant). No significant difference in GV was found between the two groups when using only self-monitored blood glucose (SMBG) data. A positive association was found between VPT and SDT in all patients (r = 0.51, P = 0.0026). CONCLUSIONS: Patients with type 1 diabetes and any MVC had significantly higher GV calculated from CGM, but not from SMBG, than patients with comparable glycemic control but without complications. This supports the hypothesis that increased GV might be associated with MVC in type 1 diabetes and that HbA1c may not describe diabetes control completely.

IGF2BP2 and IGF2 genetic effects in diabetes and diabetic nephropathy.

OBJECTIVE: The IGF2BP2 gene is located on chromosome 3q27.2 within a region linked to type 1 diabetes (T1D), type 2 diabetes (T2D) and diabetic nephropathy (DN). Its protein functionally binds to 5'-UTR of the imprinting IGF2 gene. The present study aims to evaluate the IGF2BP2-IGF2 genetic effects in diabetes and DN. MATERIALS AND METHODS: Three cohorts including T1D with and without DN (n=1139) of European descents from the GoKinD study, Swedish T1D with and without DN (n=303) and Czech control subjects without diabetes, T1D, T2D with and without DN (n=1418) were enrolled in TaqMan genotyping experiments for IGF2BP2 rs4402960 and IGF2 rs10770125. Igf2bp2 gene expression in kidney tissues of db/db and control mice at the ages of 5 and 26 weeks was examined with real time RT-PCR and Western blot. RESULTS: An association of IGF2BP2 rs4402960 with T2D in the Czech population was replicated. This IGF2BP2 polymorphism (P=0.037, OR=0.69 95% CI 0.49-0.98) was found to be associated with DN in male not in female patients with T1D selected from the GoKinD study. In the analyses of combined the GoKinD, Czech and Swedish populations, the association between IGF2BP2 polymorphism and DN in male patients with T1D was still significant (P=0.030, OR=0.73, 95% CI 0.54-0.97). IGF2 rs10770125 was also associated with DN in male T1D patients of the GoKinD population (P=0.038, OR=0.67 95% CI 0.46-0.98). There might be a genetic interaction between IGF2BP2 and IGF2 (P=0.05). The Igf2bp2 gene expression levels were increased in the kidneys of db/db mice compared to controls at the age of 5weeks but not at 26 weeks. CONCLUSIONS: The present study has replicated the association of IGF2BP2 rs4402960 with T2D in the Czech population and provided data suggesting that IGF2BP2 may have genetic interaction with IGF2 with a protective effect against DN in male patients with T1D.

Acute hyperglycemia does not impair microvascular reactivity and endothelial function during hyperinsulinemic isoglycemic and hyperglycemic clamp in type 1 diabetic patients.

AIMS: The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp. PATIENTS AND METHODS: Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L(-1)). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry. RESULTS: Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s(-1), P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s(-1), P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = -0.70, P = 0.007). CONCLUSION: Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.

Prevalence of risk factors of cardiovascular diseases in men with erectile dysfunction. Are they as frequent as we believe?

OBJECTIVES: Vascular erectile dysfunction (ED) predicts future development of cardiovascular diseases (CVD). We performed a study in men seeking consultant medical advice regarding vascular ED for the first time without a history of cardiovascular disease, diabetes mellitus or renal insufficiency. Our goal was to evaluate the prevalence of CVD risk factors in this cohort of patients. Furthermore, we assessed the prevalence of asymptomatic subclinical atherosclerosis. MATERIAL AND METHODS: All study subjects underwent a thorough physical examination including anthropometric measurements. Laboratory analyses comprising assessment of lipid spectrum, liver and kidney function tests, glycaemia and glycated haemoglobin were measured using automated analysers. Intima-media thickness of carotid arteries was measured using SONOS machine and ankle-brachial index using a mini-duplex device. CVD risk was calculated by standard SCORE charts. Chi-square test, t-test and ANOVA were used for statistical analysis. RESULTS: We examined 35 men, average age 46.5 ± 9.9 years. Six (17.1%) had a positive family history of CVD, 19 (54.3%) had dyslipidemia, 10 (28.6%) were obese, 9 (25.7%) were active smokers, and 14 (40.0%) had arterial hypertension. Eighteen (51.4%) subjects had subclinical atherosclerosis as determined by ABI and CIMT assessment. CONCLUSION: Patients with vascular erectile dysfunction have similar prevalence of CVD risk factors to general population.