Coupled action potential and calcium dynamics underlie robust spontaneous firing in dopaminergic neurons.

Dopaminergic neurons are specialized cells in the substantia nigra, tasked with dopamine secretion. This secretion relies on intracellular calcium signaling coupled to neuronal electrical activity. These neurons are known to display spontaneous calcium oscillationsin-vitroandin-vivo, even in synaptic isolation, controlling the basal dopamine levels. Here we outline a kinetic model for the ion exchange across the neuronal plasma membrane. Crucially, we relax the assumption of constant, cytoplasmic sodium and potassium concentration. We show that sodium-potassium dynamics are strongly coupled to calcium dynamics and are essential for the robustness of spontaneous firing frequency. The model predicts several regimes of electrical activity, including tonic and 'burst' oscillations, and predicts the switch between those in response to perturbations. 'Bursting' correlates with increased calcium amplitudes, while maintaining constant average, allowing for a vast change in the calcium signal responsible for dopamine secretion. All the above traits provide the flexibility to create rich action potential dynamics that are crucial for cellular function.

Insulin requirements during pregnancy in women with type 1 diabetes treated with insulin pump.

INTRODUCTION: Insulin requirement in women with Type 1 diabetes (T1DM) changes throughout pregnancy. The aim of this study was to determine the total change in insulin requirements and the effect of gestational weight gain (GWG) and pre-gestational BMI on insulin requirements during pregnancy in women with T1DM treated with continuous subcutaneous insulin infusion and continuous glucose monitoring. METHODS: This historical cohort study included all consecutive women with T1DM who were monitored during pregnancy at the high-risk pregnancy clinic at a tertiary medical center during April 2011-April 2019. One Way Repeated Measures ANOVA with Bonferroni adjustment was conducted to compare the effects of gestational age on insulin requirements and a Two Way Repeated Measures ANOVA was employed to test for the interaction between gestational age intervals and maternal BMI and GWG. RESULTS: Data regarding insulin requirements of 185 pregnancies were included in the analyses. There was a significant effect of gestational age on total insulin (Wilks' Lambda = 0.34, F(6,14) = 4.52, p = 0.009), basal insulin (Wilks' Lambda = 0.41, F(6,14) = 3.30, p = 0.031) and bolus insulin (Wilks' Lambda = 0.43, F(6,14) = 3.02, p = 0.041). Total insulin/kg requirements increased by 5.5% from 13-20 weeks to 20-26 weeks, 19% from 20-26 weeks to 26-33 weeks, and 17.4% from 26 to 33 weeks to delivery (p for trend = 0.009). Overall, insulin requirements increased by 42.1% from conception to delivery (p < 0.01). There was no significant main effect of maternal BMI or GWG on insulin requirements. CONCLUSIONS: There is a significant increase in insulin requirements per kg during pregnancy in women with T1DM who were treated with an insulin pump.

The MiniMed 780G automated insulin delivery system adapts to substantial changes in daily routine: Lessons from real world users during Ramadan.

AIM: To report on the effectiveness and safety of the MiniMed 780G automated insulin delivery system in real-world users during the month of Ramadan. MATERIALS AND METHODS: CareLink Personal data were extracted from MiniMed 780G system users from the Gulf region. Users were included if they had ≥10 days of sensor glucose data during the month of Ramadan 2022 as well as in the month before and after. For the main analysis, continuous glucose monitoring endpoints were aggregated per month and were reported by time of day (daytime: 05.31-18.00 h, and night-time). Additional analyses were performed to study the pace at which the algorithm adapts. RESULTS: Glycaemic control was well kept in the 449 included users (mean sensor glucose = 152.6 ± 18.7 mg/dl, glucose management indicator = 7.0 ± 0.4%, time in range = 70.7 ± 11.0%, time below 70 mg/dl = 2.3 ± 2.3%). Albeit some metrics differed from the month before (p < .0001 for all), absolute differences were very small and considered clinically irrelevant. During Ramadan, there was no increased risk of hypoglycaemia during daytime (time below 70 mg/dl = 2.3 ± 2.4%), time in range was highest during daytime (80.0 ± 10.7%, night: 60.4 ± 15.3%), while time above 180 mg/dl was highest during night-time (37.3 ± 16.3%, day: 17.7 ± 10.7%). The algorithm adapted immediately upon lifestyle change. CONCLUSION: The MiniMed 780G automated insulin delivery system is effective, safe and fast in adapting to the substantial changes that occur in the lifestyle of people with type 1 diabetes during Ramadan.

Parathyroid fine-needle aspiration with parathyroid hormone washout as a preoperative localisation of parathyroid adenoma-A retrospective study.

OBJECTIVE: The use of parathyroid lesion aspiration in preoperative adenoma localisation is controversial. Concerns have been raised regarding both immediate safety (hematoma, infection, alterations on a subsequent histologic preparate) and long-term safety (seeding). We aimed to evaluate the short- and long-term safety, and the efficacy, of parathyroid fine-needle aspiration with parathyroid hormone washout as a localisation modality of parathyroid adenoma in patients with primary hyperparathyroidism. DESIGN: A retrospective study. PATIENTS: The sample comprised 29 patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy at a tertiary referral centre, following localisation with parathyroid hormone washout. MEASUREMENTS: We reviewed all parathyroid hormone washout procedures performed during 2011-2021. Clinical, biochemical, and imaging information; and cytology, surgery, and pathology reports were extracted from electronic medical records. RESULTS: Parathyroid hormone levels from the needle wash were 2.1-112.5 times the upper limit of the serum norm. Other than mild neck discomfort, no immediate procedure complications were documented. Fibrotic changes and necrosis were reported in two patients, with no effect on the final pathologic diagnosis or surgery course. No long-term complications (seeding, or parathyromatosis) were found. A total of 26 (90%) patients who were operated following a positive parathyroid hormone washout result were normocalcemic at the end of a mean 38.1-month follow-up period. CONCLUSIONS: Parathyroid fine-needle aspiration with parathyroid hormone washout was accurate. Immediate, surgical, or delayed complications were not demonstrated in our series. This approach might be considered for selected patients.

The significance of coefficient of variation as a measure of hypoglycaemia risk and glycaemic control in real world users of the automated insulin delivery MiniMed 780G system.

AIM: Use of the MiniMed 780G system (MM780G) can result in a reduction in mean and standard deviation (SD) of sensor glucose (SG) values. We assessed the significance of the coefficient of variation (CV) as a measure of hypoglycaemia risk and glycaemic control. MATERIALS AND METHODS: Data from 10 404 MM780G users were analysed using multivariable logistic regression to assess the contribution of CV to (a) hypoglycaemia risk, measured as not reaching target <1% for time below range (TBR), and (b) achieving targets of time-in-range (TIR) >70% and glucose management indicator <7%. CV was compared with SD and low blood glucose index. To assess the relevance of CV <36% as a therapeutic threshold, we identified the CV cut-off point that optimally discriminated users at risk of hypoglycaemia. RESULTS: The contribution of CV was the smallest in terms of risk of hypoglycaemia (vs. low blood glucose index and SD) and TIR and glucose management indicator targets (vs. SD). In all cases the models with SD showed the best fit. A CV <43.4% (95% CI: 42.9-43.9) was the optimal cut-off point with a correct classification rate of 87.2% (vs. 72.9% for CV <36%). CONCLUSION: For MM780G users, CV is a poor marker for hypoglycaemia risk and glycaemic control. We recommend using, for the former, TBR and whether the TBR target is met (and not using CV <36% as a therapeutic threshold for hypoglycaemia); for the latter, TIR, time above range, whether targets are met and a discrete description of mean SG and SD of SG values.

Twelve-month results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closed-loop therapy outcomes versus conventional therapy in adults with type 1 diabetes.

AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy.

Real-world performance of the MiniMed 780G advanced hybrid closed loop system in Latin America: Substantial improvement in glycaemic control with each technology iteration of the MiniMed automated insulin delivery system.

AIM: We studied real-world performance of MiniMed (MM) 780G system users from Argentina, Brazil, Colombia and Chile (geographical analysis), and the effect of each technology iteration of the MM system on glycaemic control (technology iteration analysis). MATERIALS AND METHODS: CareLink data from August 2020 to September 2022 were extracted. Endpoints included continuous glucose monitoring metrics. For the geographical analysis, aggregated endpoints for MM780G system users were calculated. For the technology iteration analysis, MM780G system user outcomes were compared with outcomes when the same individuals were still using the MM640G or MM670G system. RESULTS: On average, 1025 MM780G system users from the geographical analysis were followed for 136 (SD 135) days, spent 91.5 (14.3)% in advanced hybrid closed loop, showed a glucose management indicator (GMI) of 6.7 (0.3)%, a time in range between 70 and 180 mg/dl (TIR) of 76.5 (9.0)%, and a time below range 70 mg/dl (TBR) of 2.7 (2.1)%. The percentage of users reaching targets of GMI <7%, TIR >70% and TBR <4% was 80.8%, 78.1% and 80.1%, respectively. The technology iteration analysis on users transitioning from MM640G to MM780G system (N = 381) showed 0.4% decrease in GMI (7.1% to 6.7%, p < .0001), 10.7% increase in TIR (65.9% to 76.6%, p < .0001), while TBR remained. The percentage of insulin delivered automatically increased as well (47.5%-57.7%, p < .0001). Users transitioning from MM670G system (N = 78) showed a similar but less pronounced pattern. CONCLUSIONS: Real-world Latin American MM780G users on average showed good glucose control, achieving international targets. Glycaemic control increased with every technology iteration of the MM system, providing more automation each time.

Predictors of time in target glucose range in real-world users of the MiniMed 780G system.

AIM: Automated insulin delivery systems have improved glycaemic control in people with type 1 diabetes mellitus. The analysis investigated predictors of improved sensor glucose time-in-range (TIR; 70-180 mg/dl) based on real-world use of the MiniMed 780G advanced hybrid closed-loop (AHCL) system. METHODS: Data uploaded by MiniMed 780G system users from August 2020-July 2021 were analysed using univariate and multivariable models to identify baseline, demographic and system use characteristics associated with TIR after AHCL initiation (post-AHCL). System settings associated with improved TIR post-AHCL were identified and their impact on time below range (TBR, <70 mg/dl) post-AHCL was explored. RESULTS: In total, 12 870 users were included, of which 2977 had baseline sensor glucose data. Baseline TIR and time in AHCL (defined as the percentage of time the system was in Auto-mode) were positively associated with TIR post-AHCL with larger values predicting greater mean TIR post-AHCL. Characteristics inversely associated with TIR post-AHCL included the percentage of daily basal insulin dose, daily autocorrection dose, number of daily AHCL exits triggered by the system and number of daily alarms, wherein larger values of these characteristics predicted lower mean TIR post-AHCL. System settings that predicted the largest mean TIR post-AHCL were active insulin time of 2 h and glucose target of 100 mg/dl. Active insulin time was not associated with TBR post-AHCL. CONCLUSION: Modifiable factors, including optimized pump settings, can allow users to achieve glycaemic targets with >80% TIR. The findings from this analysis will potentially guide the optimal use of the MiniMed 780G system and facilitate meaningful improvements in safe glycaemic control.

Comparison of MiniMed 780G system performance in users aged younger and older than 15 years: Evidence from 12 870 real-world users.

AIM: To investigate real-world glycaemic outcomes and goals achieved by users of the MiniMed 780G advanced hybrid closed loop (AHCL) system aged younger and older than 15 years with type 1 diabetes (T1D). MATERIALS AND METHODS: Data uploaded by MiniMed 780G system users from 27 August 2020 to 22 July 2021 were aggregated and retrospectively analysed based on self-reported age (≤15 years and >15 years) for three cohorts: (a) post-AHCL initiation, (b) 6-month longitudinal post-AHCL initiation and (c) pre- versus post-AHCL initiation. Analyses included mean percentage of time spent in AHCL and at sensor glucose ranges, insulin delivered and the proportion of users achieving recommended glucose management indicator (GMI < 7.0%) and time in target range (TIR 70-180 mg/dl > 70%) goals. RESULTS: Users aged 15 years or younger (N = 3211) achieved a GMI of 6.8% ± 0.3% and TIR of 73.9% ± 8.7%, while spending 92.7% of time in AHCL. Users aged older than 15 years (N = 8874) achieved a GMI of 6.8% ± 0.4% and TIR of 76.5% ± 9.4% with 92.3% of time in AHCL. Time spent at less than 70 mg/dl was within the recommended target of less than 4% (3.2% and 2.3%, respectively). Similar outcomes were observed for each group (N = 790 and N = 1642, respectively) in the first month following AHCL initiation, and were sustained over the 6-month observation period. CONCLUSIONS: This real-world analysis shows that more than 75% of users with T1D aged 15 years or younger using the MiniMed 780G system achieved international consensus-recommended glycaemic control, mirroring the achievements of the population aged older than 15 years.

Introduction of Steroid Absorbed Spongostan in Endoscopic Dacryocystorhinostomy Improves Success Rates.

BACKGROUND: Endoscopic Dacryocystorhinostomy (DCR) has become an acceptable alternative to the open approach, with considerable data demonstrating comparable success rates and advantages such as avoiding skin incisions. Drug-eluting bio-absorbable materials are relatively new innovation in sinus surgery, the usefulness of such materials in Endoscopic DCR is yet to be described. METHODS: A retrospective analysis of 253 endoscopic DCR procedures performed by a single surgical team from September 2011 to June 2020 was performed. At the end of 2013, a surgical modification took place with the introduction of steroid-eluting Spongostan to the intranasal surgical bed. As a result, 2 cohorts were compared before and after the modification. The first cohort consisted of 55 patients, and the second consisted of 187 patients, respectively. Patient demographics, clinical features, complications and outcomes were examined. RESULTS: A total of 242 procedures were evaluated after exclusion. In the first cohort of 55 patients (48 adults and 7 children), the overall and adult functional success rates were 83.6% and 83.3%, respectively. In the second cohort of 187 patients (167 adults and 20 children), where steroid-eluting Spongostan was used, the overall and adult functional success rates were 92.5% and 93.4%, respectively. These differences were statistically significant. CONCLUSION: This is a unique study presenting a single surgical team's experience over a 9-year period where a novel technique involving drug-eluted bio-absorbable material (Spongostan) was introduced midway through, creating 2 cohorts to compare. Success rates were significantly higher after applying steroid eluted Spongostan to our endoscopic DCR technique.

Real-world performance of the MiniMed™ 670G system in Europe.

AIM: To evaluate the real-world performance of the MiniMed 670G system in Europe, in individuals with diabetes. MATERIALS AND METHODS: Data uploaded from October 2018 to July 2020 by individuals living in Europe were aggregated and retrospectively analysed. The mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR) and above (TAR) glycaemic ranges, system use and insulin consumed in users with 10 or more days of sensor glucose data after initial Auto Mode start were determined. Another analysis based on suboptimally (GMI > 8.0%) and well-controlled (GMI < 7.0%) glycaemia pre-Auto Mode initiation was also performed. RESULTS: Users (N = 14 899) spent a mean of 81.4% of the time in Auto Mode and achieved a mean GMI of 7.0% ± 0.4%, TIR of 72.0% ± 9.7%, TBR less than 3.9 mmol/L of 2.4% ± 2.1% and TAR more than 10 mmol/L of 25.7% ± 10%, after initiating Auto Mode. When compared with pre-Auto Mode initiation, GMI was reduced by 0.3% ± 0.4% and TIR increased by 9.6% ± 9.9% (P < .0001 for both). Significantly improved glycaemic control was observed irrespective of pre-Auto Mode GMI levels of less than 7.0% or of more than 8.0%. While the total daily dose of insulin increased for both groups, a greater increase was observed in the latter, an increase primarily due to increased basal insulin delivery. By contrast, basal insulin decreased slightly in well-controlled users. CONCLUSIONS: Most MiniMed 670G system users in Europe achieved TIR more than 70% and GMI less than 7% while minimizing hypoglycaemia, in a real-world environment. These international consensus-met outcomes were enabled by automated insulin delivery meeting real-time insulin requirements adapted to each individual user.

Maternal glucose variability during pregnancy & birthweight percentile in women with pre-gestational diabetes.

INTRODUCTION: Pre-gestational diabetes mellitus (PGDM) is a major risk factor for fetal overgrowth. Interestingly, even in relatively well controlled PGDM women, as determined by average glucose indices such HbA1c, there is an increased rate of LGA (large for gestational age). Glucose variability (GV) has emerged as an important independent risk factor for several diabetes complications. The aim of this study was to determine the relationship between maternal GV indices and neonatal birth percentile. METHODS: This was a historical cohort study that included all consecutive PGDM women monitored in a single tertiary care center. Clinical and demographic variables, as well as data regarding glucose control, were prospectively recorded. Mean, standard deviation (SD) and coefficient of variance (CV) of glucose values were calculated. Pearson correlations coefficient was used to determine the correlation between glucose indices and birth percentile. The analysis was repeated after adjustment for several confounders. RESULTS: Mean birthweight and birthweight percentile were 3212 ± 532 g and 66.9%, respectively. There was a statistically significant correlation between birthweight percentile and maternal glucose SD (ß = 0.28, p = .002) and maternal glucose CV (ß = 0.21, p = .019). There was no significant correlation between birthweight percentile and mean glucose values. The association between the maternal glucose SD and birthweight percentile remained statistically significant after adjustment for maternal age, pre-pregnancy BMI and duration of diabetes. CONCLUSION: There is an association between maternal glucose variability indices (SD and CV) during pregnancy and neonatal birth percentile. Larger studies are needed to confirm these results.

[WEARING A MASK IS A PERSONAL PROTECTION AGAINST SARS-COV-2 INFECTION EVEN IN A VACCINATION-ON-BOARDING COUNTRY].

INTRODUCTION: Even with the advent of the COVID-19 vaccine, masks and social distancing are recommended as a precautionary measure to suppress SARS-CoV-2 infection and disease. In Israel, as in many other countries, despite official regulations and widespread availability and accessibility to affordable effective masks, the use of face masks is not consistent or universal. Physicians and other medical and health professionals have a vital role to play in communicating to the public about the importance of masking and encouraging people to wear face masks correctly and consistently. This review underscores the importance of masking as a protective public health mitigation measure. It describes types of face masks mainly used by the public and their effectiveness. It emphasizes the importance of identifying and addressing barriers (e.g., physical, social, economic) to encourage widespread and sustained appropriate use of masks. The article also proposes strategies to enhance masking, such as changing social norms through targeted local interventions and governmental control of mask quality and price.

Long-Time Phase Correlations Reveal Regulation of Beating Cardiomyocytes.

Spontaneous contractions of cardiomyocytes are driven by calcium oscillations due to the activity of ionic calcium channels and pumps. The beating phase is related to the time-dependent deviation of the oscillations from their average frequency, due to noise and the resulting cellular response. Here, we demonstrate experimentally that, in addition to the short-time (1-2 Hz), beat-to-beat variability, there are long-time correlations (tens of minutes) in the beating phase dynamics of isolated cardiomyocytes. Our theoretical model relates these long-time correlations to cellular regulation that restores the frequency to its average, homeostatic value in response to stochastic perturbations.

The association between novel glucose indices in parturients with type 1 diabetes mellitus and clinically significant neonatal hypoglycemia.

The aim of this study was to determine the association between glucose control indices of parturient with type 1 diabetes (T1DM), treated with an insulin pump and utilizing continuous glucose monitoring (CGM), and clinically significant neonatal hypoglycemia. This was a retrospective cohort study which included 37 pregnant women with T1DM. All women were followed at a single tertiary center and had available CGM data. The association between maternal glucose indices before delivery and the risk for neonatal hypoglycemia requiring IV glucose (clinically significant hypoglycemia) was assessed using logistic regression. Mothers to neonates that experienced clinically significant hypoglycemia had a higher glucose standard deviation (SD) before delivery than did mothers to neonates who did not (25.5 ± 13 mg/dL vs. 14.7 ± 6.7 mg/dl respectively; p = .008). This association persisted after adjustment for maternal age, maternal pregestational body mass index (BMI), gestational age at delivery, neonatal birth weight, large for gestational age (LGA) and gender. This study demonstrates an association between high maternal glucose standard deviation before delivery and the risk for clinically significant neonatal hypoglycemia. Larger studies are needed to confirm these results and further explore the role of intrapartum glucose variability in the prediction and prevention of significant neonatal hypoglycemia.

Towards Implementation of the Saint Vincent Declaration: Outcomes of Women with Pregestational Diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM. OBJECTIVES: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach. METHODS: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA). RESULTS: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts. CONCLUSIONS: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

Physics of Spontaneous Calcium Oscillations in Cardiac Cells and Their Entrainment.

Mechanical contraction in muscle cells requires Ca to allow myosin binding to actin. Beating cardiomyocytes contain internal Ca stores whose cytoplasmic concentration oscillates. Our theory explains observed single channel dynamics as well as cellular oscillations in spontaneously beating cardiomyocytes. The Ca dependence of channel activity responsible for Ca release includes positive feedback with a delayed response. We use this to predict a dynamical equation for global calcium oscillations with only a few physically relevant parameters. The theory accounts for the observed entrainment of beating to an oscillatory electric or mechanical field.

Effect of glycaemic control on cardiovascular disease in individuals with type 2 diabetes with pre-existing cardiovascular disease: A systematic review and meta-analysis.

The role of intensive glucose control in people with type 2 diabetes and pre-existing cardiovascular disease (CVD) is controversial. The aim of this systematic review and meta-analysis was to determine in a subset of people with type 2 diabetes and pre-existing CVD, the CV effect of intensive glucose control versus standard of care. We searched Medline, the Cochrane library, EMBASE and the National Institutes of Health Trial registration database for randomized controlled trials that evaluated the effect of intensive glucose control versus standard glucose control in people with type 2 diabetes on incident CVD. Data were extracted using a structured form. When data were not available in the publications, authors were contacted. Eight trials involving 8339 participants were included. Among adults with type 2 diabetes and pre-existing CVD, there was no difference in the risk of CV events in those allocated to intensive glucose control compared with those in the standard care arm (relative risk 0.98, 95% confidence interval 0.87-1.09). In conclusion, in people with diabetes and pre-existing CVD, intensive glucose control versus standard care had a neutral effect on incident CV events.

Optimal predictive low glucose management settings during physical exercise in adolescents with type 1 diabetes.

OBJECTIVES: To assess the optimal setting of the predictive low glucose management (PLGM) algorithm for preventing exercise-induced hypoglycemia in adolescents with type 1 diabetes. METHODS: Thirty-four adolescents, 15 to 20 years, wearing PLGM system, were followed during 3 days exercise during a diabetes camp. PLGM threshold was set at 70 mg/dL between 8 am and 10 pm and 90 mg/dL during 10 pm and 8 am Adolescents were divided into group A and B, with PLGM threshold at 90 and 70 mg/dL, respectively, during exercise. Time spent in hypoglycemia and AUC for time slots 8 am to 1 pm, 1 to 4 pm, 4 to 11 pm, 11 pm to 3 am, 3 to 8 am, in 3 days were compared between groups by Wilcoxon rank sum test. RESULTS: We analyzed 31 patients (median age 15.0 years, 58.1% males, median diabetes duration 7.0 years, hemoglobin A1c [HbA1c] 7.1%). No significant difference has been observed in time spent in hypoglycemia between groups using threshold 70 or 90. Time spent in target was similar in both groups, as well as time spent in hypo or hyperglycemia. The trends of blood glucose over the 3 days in the 2 groups over-lapped without significant differences. CONCLUSIONS: A PLGM threshold of 90 mg/dL during the night was associated with reduced time in hypoglycemia in adolescents doing frequent physical exercise, while maintaining 65.1% time in range during the day. However, a threshold of 70 mg/dL seems to be safe in the duration of the physical exercise. PLGM system in adolescents with type 1 diabetes was effective to prevent hypoglycemia during and after exercise, irrespective of the PLGM thresholds used.