A pragmatic randomized clinical trial of insulin glargine 300 U/mL vs first-generation basal insulin analogues in insulin-naïve adults with type 2 diabetes: 6-month outcomes of the ACHIEVE Control study.

AIMS: To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months. METHODS: In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naïve adults with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) 64 to 97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per Healthcare Effectiveness Data and Information Set (HEDIS) criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months. RESULTS: Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19, 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups. CONCLUSIONS: Among insulin-naïve adults with poorly controlled T2D, Gla-300 was associated with a statistically significantly higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (vs SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers and decision makers.

A post-hoc pooled analysis to evaluate the risk of hypoglycaemia with insulin glargine 300 U/mL (Gla-300) versus 100 U/mL (Gla-100) over wider nocturnal windows in individuals with type 2 diabetes on a basal-only insulin regimen.

The EDITION trials in type 2 diabetes demonstrated comparable glycaemic control with less nocturnal and anytime (24-hour) hypoglycaemia for insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100). However, the predefined nocturnal window (0:00-5:59 AM) may not be the most relevant for clinical practice. This post-hoc analysis compared expansions of the predefined nocturnal interval during basal insulin treatment without prandial insulin. Patient-level, 6-month data, pooled from the EDITION 2 and 3 trials and the EDITION JP 2 trial (N = 1922, basal insulin only) were analysed. Accompanying hypoglycaemia during treatment with Gla-300 was compared to that during treatment with Gla-100, using predefined (0:00-5:59 AM) and expanded (10:00 PM-5:59 AM, 0:00-7:59 AM, 10:00 PM to pre-breakfast SMPG) windows. Confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 6:00 AM and 8:00 AM. Windows expanded beyond 6:00 AM included more events than other windows. The percentage of participants with at least one event was lower with Gla-300 than Gla-100 in all windows examined. Expanding the nocturnal interval allows better assessment of the risk of hypoglycaemia associated with basal insulin. The risk of nocturnal hypoglycaemia was consistently lower with Gla-300 versus Gla-100 using all four windows.

The Diabetes Unmet Need with Basal Insulin Evaluation (DUNE) study in type 2 diabetes: Achieving HbA1c targets with basal insulin in a real-world setting.

AIMS: To describe in a real-world setting the achievement of physician-selected individualized HbA1c targets in individuals with type 2 diabetes, newly or recently initiated with basal insulin, and the association of hypoglycaemia with target achievement. MATERIALS AND METHODS: A 12-week, prospective, single-arm, observational study of adults with type 2 diabetes, either newly initiated with any basal insulin or start on basal insulin within the preceding 12 months. At enrollment, eligible participants from 28 countries were treated with or without oral antihyperglycaemic drugs and/or GLP-1 receptor agonists. RESULTS: Individualized targets for almost all of the 3139 evaluable participants (99.7%) had been set by their physicians, with 57% of participants having HbA1c targets between 7.0% and <7.5% (53 and <58 mmol/mol). By week 12, 28% and 27% of newly and previously initiated participants, respectively, achieved individualized HbA1c targets with modest average increases in daily insulin dose of 9 and 5 U (0.10 and 0.06 U/kg), respectively, from baseline (14 and 23 U [0.17 and 0.29 U/kg], respectively). Overall, 16% of participants experienced at least one episode of hypoglycaemia. Both the incidence and frequency of hypoglycaemia, but not the severity, were positively associated with a higher likelihood of achieving individualized HbA1c targets (P < 0.05). CONCLUSIONS: In this prospective real-world study, most participants using basal insulin did not achieve the individualized HbA1c targets set by their physicians. Participants who experienced symptomatic hypoglycaemia were more likely to achieve HbA1c targets than those who did not.

Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment.

AIM: To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100). MATERIALS AND METHODS: A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m2 . RESULTS: The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100 groups, for both renal function subgroups. There was a reduced risk of nocturnal (12:00-5:59 am) confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 in both renal function subgroups (eGFR <60 mL/min/1.73 m2 : relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR ≥60 mL/min/1.73 m2 : RR 0.75 [95% CI 0.67-0.85]). For confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours) the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI 0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups. CONCLUSIONS: Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced overall risk of confirmed (≤3.9 and <3.0 mmol/L [≤70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups.

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis).

In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin.

Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study.

Background and study aims The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. Patients and methods All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). Results A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m2) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Conclusion Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.

Glycaemic control and hypoglycaemia burden in patients with type 2 diabetes initiating basal insulin in Europe and the USA.

AIMS: To evaluate short- and long-term glycaemic control and hypoglycaemia incidence in insulin-naïve patients ≥30 years of age with type 2 diabetes (T2DM) initiating basal insulin (BI) with or without oral anti-hyperglycaemic drugs (OADs). METHODS: This was an observational, retrospective longitudinal analysis of electronic medical records from 5 European countries and the USA. A multivariable logistic regression model assessed baseline and short-term (0-3 months post BI initiation) factors associated with long-term (3-24 months) glycaemic control and hypoglycaemia. RESULTS: Overall, 40 627 patients were included; 20.9% and 27.8% achieved the general HbA1c target of ≤7% at 3 and 24 months post BI initiation, respectively. Failure to achieve HbA1c ≤7% at 3 months was associated with increased risk of failing to achieve target at 24 months (odds ratio [OR], 3.70 [95% CI, 3.41-4.00]). Over 24 months, 8.9% of patients experienced a recorded hypoglycaemic event. Hypoglycaemia during the initial 3-month period was associated with longer-term risk of these events over the ensuing 3 to 24 months (OR, 5.71 [95% CI, 4.67-6.99]). CONCLUSIONS: Initiating BI with or without OADs is associated with short- and long-term suboptimal glycaemic control; the majority of patients fail to achieve HbA1c target ≤7% in the first 3 months, or after 2 years of BI treatment. Treatment response and hypoglycaemia incidence by 3 months post BI initiation are associated with longer-term glycaemic control and hypoglycaemic risk, respectively. These results support the need for early anti-hyperglycaemic interventions that more effectively control blood glucose levels without increasing the risk of hypoglycaemia.

Gastroesophageal reflux disease after peroral endoscopic myotomy: Analysis of clinical, procedural and functional factors, associated with gastroesophageal reflux disease and esophagitis.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) does not include any antireflux procedure, resulting in a certain risk of iatrogenic gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the incidence of iatrogenic GERD after POEM and identify preoperative, perioperative and postoperative factors associated with GERD. METHODS: All patients treated at a single center who had a complete GERD evaluation after POEM were included in the study. Demographics, preoperative and follow-up data, results of functional studies and procedural data were collected and analyzed. RESULTS: A total of 103 patients (mean age 46.6 years, 47 males) were included. Postoperative altered esophageal acid exposure was attested in 52 patients (50.5%). A total of 19 patients (18.4%) had heartburn and 21 had esophagitis (20.4%). Overall, a clinically relevant GERD (altered esophageal acid exposure, associated with heartburn and/or esophagitis) was diagnosed in 30 patients (29.1%). Correlation between the severity of esophageal acid exposure with heartburn and esophagitis after POEM was found. Patients with heartburn had a lower postoperative 4-second integrated relaxation pressure compared to patients without symptoms (7.6 ± 3.8 mmHg vs 10.01 ± 4.4 mmHg, p<0.05). No correlations were identified with patient sex, age, postoperative body mass index, esophageal shape (sigmoid vs non sigmoid), lower esophageal sphincter pressure, length of myotomy, previous therapies and type of achalasia at high-resolution manometry. CONCLUSIONS: Preoperative, perioperative or postoperative factors minimally correlated with GERD after POEM. Clinically relevant GERD was identified in less than one-third of patients, but all patients were well controlled with medical therapy.

A randomized trial comparing the rate of hypoglycemia--assessed using continuous glucose monitoring--in 125 preschool children with type 1 diabetes treated with insulin glargine or NPH insulin (the PRESCHOOL study).

BACKGROUND: Avoidance of hypoglycemia is a key consideration in treating young children with type 1 diabetes (T1DM). KEY OBJECTIVE: To evaluate hypoglycemia with insulin glargine vs. neutral protamine Hagedorn (NPH) insulin in young children, using continuous glucose monitoring (CGM). SUBJECTS: Children of 1 to <6 yr treated with once-daily glargine vs. once- or twice-daily NPH, with bolus insulin lispro/regular human insulin provided to all. METHODS: Twenty-four week, multicenter, randomized, open-label study. Primary endpoint was event rate of composite hypoglycemia [symptomatic hypoglycemia, low CGM excursions (<3.9 mmol/L) or low fingerstick blood glucose (FSBG; <3.9 mmol/L)]. Noninferiority of glargine vs. NPH was assessed for the primary endpoint. RESULTS: One hundred and twenty-five patients (mean age, 4.2 yr) were randomized to treatment (glargine, n = 61; NPH, n = 64). At baseline, mean HbA1c was 8.0 and 8.2% with glargine and NPH, respectively. Composite hypoglycemia episodes/100 patient-yr was 1.93 for glargine and 1.69 for NPH; glargine noninferiority was not met. Events/100 patient-yr of symptomatic hypoglycemia were 0.26 for glargine vs. 0.33 for NPH; low CGM excursions 0.75 vs. 0.72; and low FSBG 1.93 vs.1.68. There was a slight difference in between-group severe/nocturnal/severe nocturnal hypoglycemia and glycemic control. All glargine-treated patients received once-daily injections; on most study days NPH-treated patients received twice-daily injections. CONCLUSIONS: While glargine noninferiority was not achieved, in young children with T1DM, there was a slight difference in hypoglycemia outcomes and glycemic control between glargine and NPH. Once-daily glargine may therefore be a feasible alternative basal insulin in young populations, in whom administering injections can be problematic.

The school-life balance effect on acquiring cross-disciplinary competences in VET: disruption or continuity during COVID-19?

Considering that teleworking and online training are on the rise following the pandemic, studying how school-life balance affects the development of VET competences in online learning during COVID-19 can provide relevant information to enhance educational equity in the future. A longitudinal study was conducted employing an on-line questionnaire to meet the following aims: to explore the development of cross-disciplinary competences in VET during COVID-19; to identify different students' profiles according to their school-life balance during the pandemic; and, to analyse whether the school-life balance was affecting competency development and propose improvements to training as a result. Results show that cross-disciplinary competences did not undergo important changes between the pre-pandemic scenario and during it, except for a decrease in metacognitive self-regulation. Similarly, most students reported having spent the same time studying before and during the pandemic. However, three main profiles of students are revealed, highlighting certain school-life imbalances. While all agree that remote teaching was critical in coping with the situation, differences were found by age and gender, with some participants experiencing more challenging situations. These results provide a fertile context for VET designers and teachers to generate new learning scenarios that meet all students' potential needs. Supplementary Information: The online version contains supplementary material available at 10.1007/s12186-023-09314-1.

A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents.

UNLABELLED: The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPARγ2(peroxisome proliferator-activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04). CONCLUSION: A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size.

Endoscopic mucosal resection of large colonic laterally spreading tumors using a dedicated viscous solution for submucosal injection (ORISE gel): a short case series (with video).

OBJECTIVE: Endoscopic mucosal resection (EMR) of large (>20 mm) laterally spreading tumors (LSTs) was usually rescheduled to guarantee experienced operator and enough endoscopic schedule time. The use of viscous solutions allows a reduction in repeated injections, snare resections and procedural time. The aim was to describe the outcome of EMR of large LSTs performed at the time of index colonoscopy, using ORISE gel (Boston Scientific). METHODS: A retrospective analysis was performed retrieving patients who underwent EMR of large colonic LSTs at the time of index colonoscopy. EMR was performed after dynamic injection of ORISE gel to create a submucosal cushion. Procedural parameters, together with pathological and endoscopic outcomes, were analyzed. RESULTS: Five patients [three males, median age 65 (45-70) years] were included. Median LST size was 35 mm (25-40). Median procedure time was 8 min (range 3-13). En bloc resection was achieved in one out of five cases; four out of five were planned as piecemeal resections. A median of 10 mL (10-20) of viscous solution was injected. R0 resection was achieved in the single case who underwent en bloc EMR, whereas it was not assessable in the case of piecemeal resections. One self-limiting bleeding was observed. CONCLUSION: The use of ORISE gel allows a well-tolerated and rapid performance of EMR of large colonic LSTs even at the time of index colonoscopy. In our opinion, in these specific situations, the use of viscous solutions is advisable and also affordable.

Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link?

UNLABELLED: Fatty liver is increasingly common in obese adolescents. We determined its association with glucose dysregulation in 118 (37M/81F) obese adolescents of similar age and percent total fat. Fast-magnetic resonance imaging (MRI) and simple MRI were used to quantify hepatic fat content and abdominal fat distribution. All subjects had a standard oral glucose tolerance test. Insulin sensitivity was estimated by the Matsuda Index and homeostasis model assessment of insulin resistance. Baseline total and high molecular weight (HMW)-adiponectin and interleukin (IL)-6 levels were measured. The cohort was stratified according to tertiles of hepatic fat content. Whereas age and %fat were comparable across tertiles, ethnicity differed in that fewer Blacks and more Whites and Hispanics were in the moderate and high category of hepatic fat fraction (HFF). Visceral and the visceral-to-subcutaneous fat ratio increased and insulin sensitivity decreased across tertiles. Two-hour plasma glucose rose with increasing hepatic steatosis (P < 0.008). 73.7% of the subjects in the high HFF had the metabolic syndrome compared to 19.5% and 30.6%, respectively, in the low and moderate categories. Both total and HMW-adiponectin decreased, and IL-6 increased with increasing hepatic steatosis. CONCLUSION: In obese adolescents, independent of total fat, increasing severity of fatty liver is associated with glucose dysregulation, metabolic syndrome, and with a proinflammatory milieu.

Low Blood Glucose Index and Hypoglycaemia Risk: Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in Type 2 Diabetes.

INTRODUCTION: We examined differences in hypoglycaemia risk between insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100) in individuals with type 2 diabetes (T2DM) using the low blood glucose index (LBGI). METHODS: Daily profiles of self-monitored plasma glucose (SMPG) from the EDITION 2, EDITION 3 and SENIOR treat-to-target trials of Gla-300 versus Gla-100 were used to compute the LBGI, which is an established metric of hypoglycaemia risk. The analysis also examined documented (blood glucose readings < 3.0 mmol/L [54 mg/dL]) symptomatic hypoglycaemia (DSH). RESULTS: Overall LBGI in EDITION 2 and SENIOR and night-time LBGI in all three trials were significantly (p < 0.05) lower with Gla-300 versus Gla-100. The largest differences between Gla-300 and Gla-100 were observed during the night. In all three trials, individual LBGI results correlated with the observed number of DSH episodes per participant (EDITION 2 [r = 0.35, p < 0.001]; EDITION 3 [r = 0.26, p < 0.001]; SENIOR [r = 0.30, p < 0.001]). Participants at moderate risk of experiencing hypoglycaemia (defined as LBGI > 1.1) reported 4- to 8-fold more frequent DSH events than those at minimal risk (LBGI ≤ 1.1) (p ≤ 0.009). CONCLUSIONS: The LBGI identified individuals with T2DM at risk for hypoglycaemia using SMPG data and correlated with the number of DSH events. Using the LBGI metric, a lower risk of hypoglycaemia with Gla-300 than Gla-100 was observed in all three trials. The finding that differences in LBGI are greater at night is consistent with previously published differences in the pharmacokinetic profiles of Gla-300 and Gla-100, which provides the physiological foundation for the presented results.

Real-world outcomes of treatment with insulin glargine 300 U/mL versus standard-of-care in people with uncontrolled type 2 diabetes mellitus.

Objective: To compare real-world outcomes with newer (insulin glargine 300 U/mL; Gla-300) versus standard of care (SoC) basal insulins (BIs) in the REACH (insulin-naïve; NCT02967224) and REGAIN (basal insulin-treated; NCT02967211) studies in participants with uncontrolled type 2 diabetes (T2DM) in Europe and Brazil.Methods: In these open-label, parallel-group, pragmatic studies, patients (HbA1c > 7.0%) were randomized to Gla-300 or SoC BI for a 6-month treatment period (to demonstrate non-inferiority of Gla-300 vs SoC BIs for HbA1c change [non-inferiority margin 0.3%]) and a 6-month extension period (continuing with their assigned treatment). Insulin titration/other medication changes were at investigator/patient discretion post-randomization.Results: Overall, 703 patients were randomized to treatment in REACH (Gla-300, n = 352; SoC, n = 351) and 609 (Gla-300, n = 305, SoC, n = 304) in REGAIN. The primary outcome, non-inferiority of Gla-300 versus SoC for HbA1c change from baseline to month 6, was met in REACH (least squares [LS] mean difference 0.12% [95% CI -0.046 to 0.281]) but not REGAIN (LS mean difference 0.17% [0.015-0.329]); no between-treatment difference in HbA1c change was shown after 12 months in either study. BI dose increased minimally from baseline to 12 months in REACH (Gla-300, +0.17 U/kg; SoC, +0.15 U/kg) and REGAIN (Gla-300, +0.11 U/kg; SoC, +0.07 U/kg). Hypoglycemia incidence was low and similar between treatment arms in both studies.Conclusions: In both REACH and REGAIN, no differences in glycemic control or hypoglycemia outcomes with Gla-300 versus SoC BIs were seen over 12 months. However, the suboptimal insulin titration in REACH and REGAIN limits comparisons of outcomes between treatment arms and suggests that more titration instruction/support may be required for patients to fully derive the benefits from newer basal insulin formulations.

Ectopic fat deposition and the metabolic syndrome in obese children and adolescents.

AIMS: We examined the impact of varying degrees of obesity on the prevalence of the metabolic syndrome and its relation to ectopic fat deposition in a large, multi-ethnic cohort of children and adolescents. METHODS: A standard glucose tolerance test was administered to 438 obese, 31 overweight and 20 nonobese children and adolescents. Baseline measures included blood pressure and plasma lipid and insulin levels. In a subset of 118 subjects, abdominal fat distribution was measured by magnetic resonance imaging (MRI) and further stratified into tertiles based on the proportion of abdominal fat in the visceral depot. Liver fat was measured by fast MRI and intramyocellular fat by proton magnetic resonance spectroscopy. RESULTS: Overall, the prevalence of the metabolic syndrome increased with the severity of obesity. In the subset of 118 obese adolescents undergoing MRI, there were no differences in age or body mass index z-scores across tertiles. However, as the proportion of visceral fat increased, subcutaneous fat decreased. There were significant increases in the occurrence of hepatic steatosis, insulin resistance and metabolic syndrome, with subjects in tertile 3 being 5.2-times more likely to have the metabolic syndrome than those in tertile 1. CONCLUSIONS: The prevalence of the metabolic syndrome is high in obese children and adolescents and increases with worsening obesity. Obese adolescents with a high proportion of visceral fat and relatively low abdominal subcutaneous fat have a phenotype reminiscent of partial lipodystrophy: hepatic steatosis, profound insulin resistance and an increased risk of the metabolic syndrome.

Online vs. Classroom Learning: Examining Motivational and Self-Regulated Learning Strategies Among Vocational Education and Training Students.

Numerous studies have been conducted to explore students' employment of motivational and self-regulated learning strategies (SRL). Research highlights the importance of having motivated students equipped with strategies that help them self-regulate their learning, this being highly important when learning is acquired through online learning programs. Nonetheless, such research has been scarce with Vocational Education and Training (VET) students; this is the gap in the literature this paper aims to address. The article analyzes the degree to which VET students employ motivational and SRL strategies by comparing them according to the learning mode chosen. To achieve this, a quantitative approach was adopted to carry out a cross-sectional study. A total of 577 first-year VET students responded to an online questionnaire based on some of the motivational and SRL strategies scale included in Pintrich's model. Statistical analyses were applied to test two hypotheses. Pintrich's model was validated through a confirmatory factor analysis considering its application to Catalan VET students for the first time. The results reveal significant differences between classroom and online students in terms of levels of metacognitive self-regulation and effort regulation when starting a VET program. However, this difference might not be entirely explained by the learning mode chosen. The findings of this study will provide VET researchers and practitioners with a greater understanding of their students' characteristics when starting the program and the means to develop strategies that ensure their engagement throughout the course.

Obesity in children and adolescents.

CONTEXT: Although the prevalence rates of childhood obesity have seemingly been stable over the past few years, far too many children and adolescents are still obese. Childhood obesity, and its associated metabolic complications, is rapidly emerging as one of the greatest global challenges of the 21st century. About 110 million children are now classified as overweight or obese. EVIDENCE ACQUISITION: In this review we first describe the most recent data on the prevalence, severity, and racial/ethnic differences in childhood obesity. Obesity is associated with significant health problems in the pediatric age group and is an important early risk factor for much of adult morbidity and mortality. EVIDENCE SYNTHESIS: We review the metabolic complications associated with childhood obesity. Particular emphasis is given to the description of studies regarding the impact of varying degrees of obesity on the cardiometabolic risk factors in youth. We further describe studies in obese adolescents that have examined the importance of ectopic lipid deposition in the visceral abdominal depot and in insulin sensitive tissues in relation to the presence of insulin resistance. We end by describing studies that have examined beta-cell function in obese adolescents with normal glucose tolerance. CONCLUSIONS: The growing number of obese children and adolescents worldwide is of great concern. Many obese children and adolescents already manifest some metabolic complications, and these children are at high risk for the development of early morbidity. Understanding the underlying pathogenesis of this peculiar phenotype is of critical importance.

Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents.

OBJECTIVE: The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth. RESEARCH DESIGN AND METHODS: We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups. RESULTS: Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r(2) = 25.9%). CONCLUSIONS: IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion.