Comparing Patch vs Pen Bolus Insulin Delivery in Type 2 Diabetes Using Continuous Glucose Monitoring Metrics and Profiles

OBJECTIVE: CeQur Simplicity™ (CeQur, Marlborough, MA) is a 3-day insulin delivery patch designed to meet mealtime insulin requirements. A recently reported 48-week, randomized, multicenter, interventional trial compared efficacy, safety and self-reported outcomes in 278 adults with type 2 diabetes (T2D) on basal insulin therapy who initiated and managed mealtime insulin therapy with a patch pump versus insulin pen. We assessed changes in key glycemic metrics among a subset of patients who wore a continuous glucose monitoring (CGM) device. METHODS: Study participants (patch, n = 49; pen, n = 48) wore a CGM device in masked setting during the baseline period and prior to week 24. Glycemic control was assessed using international consensus guidelines for percentage of Time In Range (%TIR: \u3e70% at 70-180 mg/dL), Time Below Range (%TBR: \u3c4% at \u3c70 mg/dL; \u3c1% at \u3c54 mg/dL), and Time Above Range (%TAR: \u3c25% at \u3e180 mg/dL; \u3c5% at \u3e250 mg/dL). RESULTS: Both the patch and pen groups achieved recommended targets in %TIR (74.1% ± 18.7%, 75.2 ± 16.1%, respectively) and marked reductions in %TAR \u3e180 mg/dL (21.1% ± 19.9%, 19.7% ± 17.5%, respectively) but with increased %TBR \u3c70 mg/dL (4.7% ± 5.2%, 5.1 ± 5.8, respectively), all P \u3c .0001. No significant between-group differences in glycemic improvements or adverse events were observed. CONCLUSIONS: CGM confirmed that the patch or pen can be used to safely initiate and optimize basal-bolus therapy using a simple insulin adjustment algorithm with SMBG. Preference data suggest that use of the patch vs pen may enhance treatment adherence

Implementation of Basal-Bolus Therapy in Type 2 Diabetes:A Randomized Controlled Trial Comparing Bolus Insulin Delivery Using an Insulin Patch with an Insulin Pen

Background: Barriers to mealtime insulin include complexity, fear of injections, and lifestyle interference. This multicenter, randomized controlled trial evaluated efficacy, safety, and self-reported outcomes in adults with type 2 diabetes, inadequately controlled on basal insulin, initiating and managing mealtime insulin with a wearable patch versus an insulin pen. Methods: Adults with type 2 diabetes (n = 278, age: 59.2 +/- 8.9 years), were randomized to patch (n = 139) versus pen (n = 139) for 48 weeks, with crossover at week 44. Baseline insulin was divided 1:1 basal: bolus. Using a pattern-control logbook, subjects adjusted basal and bolus insulin weekly using fasting and premeal glucose targets. Results: Glycated hemoglobin (HbA1c) change (least squares mean +/- standard error) from baseline to week 24 (primary endpoint) improved (P \u3c 0.0001) in both arms, -1.7% +/- 0.1% and -1.6% +/- 0.1% for patch and pen (-18.6 +/- 1.1 and -17.5 +/- 1.1 mmol/mol), and was maintained at 44 weeks. The coefficient of variation of 7-point self-monitoring blood glucose decreased more (P = 0.02) from baseline to week 44 for patch versus pen. There were no differences in adverse events, including hypoglycemia (three severe episodes per arm), and changes in weight and insulin doses. Subject-reported treatment satisfaction, quality of life, experience ratings at week 24, and device preferences at week 48 significantly favored the patch. Most health care providers preferred patch for mealtime insulin. Conclusions: Bolus insulin delivered by patch and pen using an algorithm-based weekly insulin dose titration significantly improved HbA1c in adults with type 2 diabetes, with improved subject and health care provider experience and preference for the patch

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Carotid intima-media and adventitial thickening: comparison of new and established ultrasound and magnetic resonance imaging techniques

[DOI:\hrefhttps://dx.doi.org/10.1016/j.atherosclerosis.2010.12.03610.1016/j.atherosclerosis.2010.12.036] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2130035521300355]Carotid intima-media thickness is a well established non-invasive surrogate marker of cardiovascular disease, however there is evidence that structural modification of the arterial adventitia also accompanies cardiovascular risk factors and might be involved causally in atherosclerosis. We sought to determine the relative contributions of the intima-media and adventitia to variation in ultrasound and magnetic resonance derived measures of carotid wall thickness.\ Carotid ultrasound and magnetic resonance imaging were undertaken in 20 participants. Carotid intima-media thickness, carotid extra-media thickness (which incorporates the arterial adventitia) and total wall thickness (a combined near-wall intima-media thickness and carotid extra-media thickness) using high-resolution ultrasound, and wall thickness using magnetic resonance imaging, were obtained.\ All ultrasound-derived measures of the arterial wall thickness were highly correlated with wall thickness by magnetic resonance imaging (all P<0.001); as expected the total wall thickness by ultrasound measure was most tightly correlated (correlation coefficient=0.814, P<0.0001). In multivariable models, there was evidence that both carotid intima-media thickness and carotid extra-media thickness contributed independently to the variance in wall thickness by magnetic resonance imaging, especially for the most severe focal thickening. Measures of carotid wall thickness that incorporated all three layers of the arterial wall were more closely correlated with the number of cardiovascular risk factors than carotid intima-media thickness alone.\ These results indicate that the arterial adventitia is an important contributor to the wall thickness measure derived by magnetic resonance imaging, and that carotid extra-media thickness likely provides additional information concerning arterial structure than that obtained from carotid intima-media thickness alone

The reliability of high resolution MRI in the measurement of early stage carotid wall thickening

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Noninvasive assessment of the prevalence and characteristics of coronary atherosclerotic plaques by multidetector computed tomography in asymptomatic type 2 diabetic patients at high risk of significant coronary artery disease: A preliminary study

SummaryBackgroundThere is a need to identify diabetic patients at risk of cardiovascular events before symptom onset.AimsTo evaluate the prevalence and characteristics of coronary atherosclerotic plaques in asymptomatic type 2 diabetic patients with coronary risk factors but without known coronary artery disease, using multidetector computed tomography.MethodsHigh-resolution 40-slice coronary computed tomography was performed prospectively in 42 consecutive type 2 diabetic patients (mean age 62 years; range 50–77 years; 28 men) with over one or more carotid atherosclerotic plaque and no coronary artery disease symptoms. Computed tomography data were evaluated for calcium score and the presence of coronary plaques. Plaque type, distribution, extensive character and obstructive nature were determined per patient for each segment.ResultsNo plaques were detected in 11 (26.2%) patients. Atherosclerotic plaques were detected in 31 (73.8%) patients. A total of 147 coronary segments with plaque were identified, of which 11 (7.5%) contained hypodense plaques, 28 (19%) mixed plaques and 108 (73.5%) calcified plaques. Hypodense plaques were noted in 4/15 (26.7%) patients without coronary calcifications. Most calcified and hypodense plaques resulted in lumen narrowing of less than 50%; most mixed plaques resulted in lumen narrowing greater than 50%. Obstructive disease was detected in 9/11 patients with a high calcium score (>400).ConclusionThis preliminary study demonstrates that a high proportion of asymptomatic type 2 diabetic patients present without coronary plaques detectable by multidetector computed tomography, despite concomitant carotid atherosclerotic lesions. Computed tomography seems to detect a high proportion of plaques compared with conventional angiography in these specific patients

Increased levels of endothelial microparticles CD144 (VE-Cadherin) positives in type 2 diabetic patients with coronary noncalcified plaques evaluated by multidetector computed tomography (MDCT)

articleObjective: The combination of both morphological and cellular markers of subclinical atherosclerosis, in addition to conventional risk factors, may help to improve cardiovascular prevention in type 2 diabetic patients. The aim of our cross-sectional study was to evidence a putative increase in endothelial (EMP) or platelet (PMP) microparticles, in type 2 diabetic patients with coronary noncalcified plaques detected by multidetector CT (MDCT).Methods and results: Microparticles and coronary MDCT were assessed in 56 type 2 diabetic patients with different cardiovascular risk levels. Both EMP (r=0.35, p=0.022) and PMP (rho=0.34, p=0.022) were correlated with hsCRP. EMP were elevated in patients with acute coronary syndromes (p=0.034). EMP count was significantly higher in the presence of noncalcified diseased segments (p=0.01). By contrast, there was no association between hsCRP and noncalcified atheroma. This increase in EMP in noncalcified diseased segment carriers remained borderline significant after adjustment for coronary heart disease and hsCRP. Conversely, there was no association of PMP count with noncalcified diseased segments and no difference in PMP count between patients with and without acute coronary syndrome. No significant association between either EMP and PMP counts and mixed or calcified diseased segments was observed.Conclusions: We report for the first time an association between plasma EMP-CD144+ and coronary noncalcified plaques assessed by MDCT in a population of type 2 diabetic patients. EMP might be used as a surrogate marker of unstable plaques, and might help to improve cardiovascular prediction in diabetic patients with intermediate risk

Childhood/adult-onset lysosomal acid lipase deficiency: A serious metabolic and vascular phenotype beyond liver disease-four new pediatric cases

International audienceBACKGROUND: The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity. OBJECTIVE: To assess 4 new pediatric cases of late-onset LALD with an evaluation of hepatic, metabolic, and vascular evolution under statin. METHODS: Four patients were retrospectively described. Anthropometric data (weight, height, and body mass index) and laboratory data (LIPA mutations, acid lipase residual activity, liver and lipid profile, and homeostatic model assessment index) were collected. Liver histology was assessed by the noninvasive tests FibroScan and FibroTest and confirmed by liver biopsy. Vascular impact was followed up by carotid intima-media thickness (cIMT) assessment. RESULTS: The 4 cases of late-onset LALD came from 2 families, each with a boy (aged 8.6 and 11 years at diagnosis) and a girl (aged 10.6 and 13 years at diagnosis). Treatment with statins was performed for 8 and 5 years, respectively, from diagnosis. Statins decreased the low-density lipoprotein cholesterol mean value of 40%. All children showed significant liver fibrosis (F3 [n = 3]; F2 [n = 1]). cIMT showed the following for all children: abnormal measures without improvement and atherosclerotic plaques. One child developed a deleterious metabolic phenotype with obesity and insulin resistance (homeostatic model assessment = 3.08) associated with higher mean hepatic transaminases (149 vs 98, 88, and 61 IU/L) and increased mean cIMT values (raising from 0.47 to 0.5 mm vs 0.43 and 0.43 mm). CONCLUSION: Late-onset LALD is a rare metabolic disease with a larger impact than liver disease. Our work shows the importance of having a global metabolic view and to evaluate the cardiovascular impact of the new enzymatic treatment. (C) 2016 National Lipid Association. All rights reserved