Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were ≥18 years (≥20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA1c 53-86 mmol/mol (7.0-10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA1c and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. RESULTS: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA1c and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA1c than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were -11 (-13, -9) mmol/mol, -16 (-18, -13) mmol/mol and -17 (-19, -15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were -1.0 (-1.2, -0.8), -1.4 (-1.6, -1.2) and -1.5 (-1.8, -1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] -1.2 kg [-2.0 kg, -0.4 kg; p<0.01] and -2.0 kg [-2.8 kg, -1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] -0.0 kg [-0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA1c and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. CONCLUSIONS/INTERPRETATION: Oral semaglutide resulted in significantly greater reductions in HbA1c across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04109547. FUNDING: Novo Nordisk A/S.

Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial.

AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS). RESULTS: Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity. CONCLUSIONS/INTERPRETATION: Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04017832. FUNDING: This trial was funded by Novo Nordisk A/S, Søborg, Denmark.

Continuous glucose monitoring in adults with type 2 diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) is increasingly used in the treatment of type 2 diabetes, but the effects on glycaemic control are unclear. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the effect of CGM on glycaemic control in adults with type 2 diabetes. METHODS: We performed a systematic review using Embase, MEDLINE, Web of Science, Scopus and ClinicalTrials.gov from inception until 2 May 2023. We included RCTs investigating real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) compared with self-monitoring of blood glucose (SMBG) in adults with type 2 diabetes. Studies with an intervention duration <6 weeks or investigating professional CGM, a combination of CGM and additional glucose-lowering treatment strategies or GlucoWatch were not eligible. Change in HbA1c and the CGM metrics time in range (TIR), time below range (TBR), time above range (TAR) and glycaemic variability were extracted. We evaluated the risk of bias using the Cochrane risk-of-bias tool version 2. Data were synthesised by performing a meta-analysis. We also explored the effects of CGM on severe hypoglycaemia and micro- and macrovascular complications. RESULTS: We found 12 RCTs comprising 1248 participants, with eight investigating rtCGM and four isCGM. Compared with SMBG, CGM use (rtCGM or isCGM) led to a mean difference (MD) in HbA1c of -3.43 mmol/mol (-0.31%; 95% CI -4.75, -2.11, p<0.00001, I2=15%; moderate certainty). This effect was comparable in studies that included individuals using insulin with or without oral agents (MD -3.27 mmol/mol [-0.30%]; 95% CI -6.22, -0.31, p=0.03, I2=55%), and individuals using oral agents only (MD -3.22 mmol/mol [-0.29%]; 95% CI -5.39, -1.05, p=0.004, I2=0%). Use of rtCGM showed a trend towards a larger effect (MD -3.95 mmol/mol [-0.36%]; 95% CI -5.46 to -2.44, p<0.00001, I2=0%) than use of isCGM (MD -1.79 mmol/mol [-0.16%]; 95% CI -5.28, 1.69, p=0.31, I2=64%). CGM was also associated with an increase in TIR (+6.36%; 95% CI +2.48, +10.24, p=0.001, I2=9%) and a decrease in TBR (-0.66%; 95% CI -1.21, -0.12, p=0.02, I2=45%), TAR (-5.86%; 95% CI -10.88, -0.84, p=0.02, I2=37%) and glycaemic variability (-1.47%; 95% CI -2.94, -0.01, p=0.05, I2=0%). Three studies reported one or more events of severe hypoglycaemia and macrovascular complications. In comparison with SMBG, CGM use led to a non-statistically significant difference in the incidence of severe hypoglycaemia (RR 0.66, 95% CI 0.15, 3.00, p=0.57, I2=0%) and macrovascular complications (RR 1.54, 95% CI 0.42, 5.72, p=0.52, I2=29%). No trials reported data on microvascular complications. CONCLUSIONS/INTERPRETATION: CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce. REGISTRATION: This systematic review was registered on PROSPERO (ID CRD42023418005).

Associations of 24 h time-use compositions of sitting, standing, physical activity and sleeping with optimal cardiometabolic risk and glycaemic control: The Maastricht Study.

AIMS/HYPOTHESIS: The associations of sitting, standing, physical activity and sleep with cardiometabolic health and glycaemic control markers are interrelated. We aimed to identify 24 h time-use compositions associated with optimal metabolic and glycaemic control and determine whether these varied by diabetes status. METHODS: Thigh-worn activPAL data from 2388 participants aged 40-75 years (48.7% female; mean age 60.1 [SD = 8.1] years; n=684 with type 2 diabetes) in The Maastricht Study were examined. Compositional isometric log ratios were generated from mean 24 h time use (sitting, standing, light-intensity physical activity [LPA], moderate-to-vigorous physical activity [MVPA] and sleeping) and regressed with outcomes of waist circumference, fasting plasma glucose (FPG), 2 h plasma glucose, HbA1c, the Matsuda index expressed as z scores, and with a clustered cardiometabolic risk score. Overall analyses were adjusted for demographics, smoking, dietary intake and diabetes status, and interaction by diabetes status was examined separately. The estimated difference when substituting 30 min of one behaviour with another was determined with isotemporal substitution. To identify optimal time use, all combinations of 24 h compositions possible within the study footprint (1st-99th percentile of each behaviour) were investigated to determine those cross-sectionally associated with the most-optimal outcome (top 5%) for each outcome measure. RESULTS: Compositions lower in sitting time and with greater standing time, physical activity and sleeping had the most beneficial associations with outcomes. Associations were stronger in participants with type 2 diabetes (p<0.05 for interactions), with larger estimated benefits for waist circumference, FPG and HbA1c when sitting was replaced by LPA or MVPA in those with type 2 diabetes vs the overall sample. The mean (range) optimal compositions of 24 h time use, considering all outcomes, were 6 h (range 5 h 40 min-7 h 10 min) for sitting, 5 h 10 min (4 h 10 min-6 h 10 min) for standing, 2 h 10 min (2 h-2 h 20 min) for LPA, 2 h 10 min (1 h 40 min-2 h 20 min) for MVPA and 8 h 20 min (7 h 30 min-9 h) for sleeping. CONCLUSIONS/INTERPRETATION: Shorter sitting time and more time spent standing, undergoing physical activity and sleeping are associated with preferable cardiometabolic health. The substitutions of behavioural time use were significantly stronger in their associations with glycaemic control in those with type 2 diabetes compared with those with normoglycaemic metabolism, especially when sitting time was balanced with greater physical activity.

Heterogeneity of glycaemic phenotypes in type 1 diabetes.

AIMS/HYPOTHESIS: Our study aims to uncover glycaemic phenotype heterogeneity in type 1 diabetes. METHODS: In the Study of the French-speaking Society of Type 1 Diabetes (SFDT1), we characterised glycaemic heterogeneity thanks to a set of complementary metrics: HbA1c, time in range (TIR), time below range (TBR), CV, Gold score and glycaemia risk index (GRI). Applying the Discriminative Dimensionality Reduction with Trees (DDRTree) algorithm, we created a phenotypic tree, i.e. a 2D visual mapping. We also carried out a clustering analysis for comparison. RESULTS: We included 618 participants with type 1 diabetes (52.9% men, mean age 40.6 years [SD 14.1]). Our phenotypic tree identified seven glycaemic phenotypes. The 2D phenotypic tree comprised a main branch in the proximal region and glycaemic phenotypes in the distal areas. Dimension 1, the horizontal dimension, was positively associated with GRI (coefficient [95% CI]) (0.54 [0.52, 0.57]), HbA1c (0.39 [0.35, 0.42]), CV (0.24 [0.19, 0.28]) and TBR (0.11 [0.06, 0.15]), and negatively with TIR (-0.52 [-0.54, -0.49]). The vertical dimension was positively associated with TBR (0.41 [0.38, 0.44]), CV (0.40 [0.37, 0.43]), TIR (0.16 [0.12, 0.20]), Gold score (0.10 [0.06, 0.15]) and GRI (0.06 [0.02, 0.11]), and negatively with HbA1c (-0.21 [-0.25, -0.17]). Notably, socioeconomic factors, cardiovascular risk indicators, retinopathy and treatment strategy were significant determinants of glycaemic phenotype diversity. The phenotypic tree enabled more granularity than traditional clustering in revealing clinically relevant subgroups of people with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our study advances the current understanding of the complex glycaemic profile in people with type 1 diabetes and suggests that strategies based on isolated glycaemic metrics might not capture the complexity of the glycaemic phenotypes in real life. Relying on these phenotypes could improve patient stratification in type 1 diabetes care and personalise disease management.

Practical considerations for continuous glucose monitoring in elite athletes with type 1 diabetes mellitus: A narrative review.

Type 1 diabetes mellitus (T1DM) refers to a metabolic condition where a lack of insulin impairs the usual homeostatic mechanisms to control blood glucose levels. Historically, participation in competitive sport has posed a challenge for those with T1DM, where the dynamic changes in blood glucose during exercise can result in dangerously high (hyperglycaemia) or low blood glucoses (hypoglycaemia) levels. Over the last decade, research and technological development has enhanced the methods of monitoring and managing blood glucose levels, thus reducing the chances of experiencing hyper- or hypoglycaemia during exercise. The introduction of continuous glucose monitoring (CGM) systems means that glucose can be monitored conveniently, without the need for frequent fingerpick glucose checks. CGM devices include a fine sensor inserted under the skin, measuring levels of glucose in the interstitial fluid. Readings can be synchronized to a reader or mobile phone app as often as every 1-5 min. Use of CGM devices is associated with lower HbA1c and a reduction in hypoglycaemic events, promoting overall health and athletic performance. However, there are limitations to CGM, which must be considered when being used by an athlete with T1DM. These limitations can be addressed by individualized education plans, using protective equipment to prevent sensor dislodgement, as well as further research aiming to: (i) account for disparities between CGM and true blood glucose levels during vigorous exercise; (ii) investigate the effects of temperature and altitude on CGM accuracy, and (iii) explore of the sociological impact of CGM use amongst sportspeople without diabetes on those with T1DM.

Daily blood flow restriction does not preserve muscle mass and strength during 2 weeks of bed rest.

We measured the impact of blood flow restriction on muscle protein synthesis rates, muscle mass and strength during 2 weeks of strict bed rest. Twelve healthy, male adults (age: 24 ± 3 years, body mass index: 23.7 ± 3.1 kg/m2 ) were subjected to 14 days of strict bed rest with unilateral blood flow restriction performed three times daily in three 5 min cycles (200 mmHg). Participants consumed deuterium oxide and we collected blood and saliva samples throughout 2 weeks of bed rest. Before and immediately after bed rest, lean body mass (dual-energy X-ray absorptiometry scan) and thigh muscle volume (magnetic resonance imaging scan) were assessed in both the blood flow restricted (BFR) and control (CON) leg. Muscle biopsies were collected and unilateral muscle strength (one-repetition maximum; 1RM) was assessed for both legs before and after the bed rest period. Bed rest resulted in 1.8 ± 1.0 kg lean body mass loss (P < 0.001). Thigh muscle volume declined from 7.1 ± 1.1 to 6.7 ± 1.0 L in CON and from 7.0 ± 1.1 to 6.7 ± 1.0 L in BFR (P < 0.001), with no differences between treatments (P = 0.497). In addition, 1RM leg extension strength decreased from 60.2 ± 10.6 to 54.8 ± 10.9 kg in CON and from 59.2 ± 12.1 to 52.9 ± 12.0 kg in BFR (P = 0.014), with no differences between treatments (P = 0.594). Muscle protein synthesis rates during bed rest did not differ between the BFR and CON leg (1.11 ± 0.12 vs. 1.08 ± 0.13%/day, respectively; P = 0.302). Two weeks of bed rest substantially reduces skeletal muscle mass and strength. Blood flow restriction during bed rest does not modulate daily muscle protein synthesis rates and does not preserve muscle mass or strength. KEY POINTS: Bed rest, often necessary for recovery from illness or injury, leads to the loss of muscle mass and strength. It has been postulated that blood flow restriction may attenuate the loss of muscle mass and strength during bed rest. We investigated the effect of blood flow restriction on muscle protein synthesis rates, muscle mass and strength during 2 weeks of strict bed rest. Blood flow restriction applied during bed rest does not modulate daily muscle protein synthesis rates and does not preserve muscle mass or strength. Blood flow restriction is not effective in preventing muscle atrophy during a prolonged period of bed rest.

Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study.

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.

The use of dietary supplements, and the association between supplemental vitamin D and glycaemic control in adult individuals with type 1 diabetes.

AIMS: To assess the dietary supplement use in adult individuals with type 1 diabetes, and to study the association between vitamin D supplementation and glycaemic control in an observational cross-sectional study. METHODS: The study subjects were participants of the Finnish Diabetic Nephropathy Study. Data were included from all individuals with type 1 diabetes with estimated glomerular filtration rate ≥60 mL/min/1.73 m2, who had completed a diet questionnaire. In the questionnaire, the participants reported dietary supplement use for the past 30 days. A thorough investigation with an assessment of the blood panel was conducted at the study visit. RESULTS: Data were available from 1181 individuals (43% men, mean ± SD age 45 ± 13 years). Altogether 62% of the sample reported supplement use; 56% reported some vitamin or mineral and 27% reported non-vitamin and non-mineral supplement use. Supplement use was more frequent among women and those supplementing had better overall health. In the study sample, of the vitamins and minerals, vitamin D (45%) and magnesium (31%), respectively, were the most frequently reported. In the multivariable models, vitamin D supplementation was associated with better glycaemic control. Starting from a daily dose of ≥30 µg, there was evidence of improving glycaemic control with higher doses of supplemental vitamin D (e.g., for 30 µg: B [Wald Confidence Internal], p-value, -2.76 [-5.03 to -0.49], 0.017). CONCLUSIONS: Supplement use was frequent in this sample of adult individuals with type 1 diabetes. Due to potential drug-supplement interactions, the attending physicians should be aware of their patients' supplement use. The causality between vitamin D supplementation and glycaemic control should be assessed in a randomized controlled trial.

Do-it-yourself continuous glucose monitoring in people aged 16 to 69 years with type 1 diabetes: A qualitative study.

AIMS: In many countries, real-time continuous glucose monitoring (rt-CGM) is not funded, and cost presents a barrier to access. A do-it-yourself conversion of intermittently scanned CGM (DIY-CGM) is a cheaper alternative. This qualitative study aimed to explore user experiences with DIY-CGM in people aged 16 to 69 years with type 1 diabetes (T1D). METHODS: Convenience sampling was used to recruit participants for semi-structured virtual interviews exploring experiences of DIY-CGM use. Participants were recruited after completing the intervention arm of a crossover randomised controlled trial that evaluated DIY-CGM versus intermittently scanned CGM (isCGM). Participants were previously naive to DIY-CGM and rt-CGM but not isCGM. The DIY-CGM intervention consisted of a Bluetooth bridge connected to isCGM, adding rt-CGM functionality over 8 weeks. Interviews were transcribed, then thematic analysis was performed. RESULTS: Interviews were with 12 people aged 16 to 65 years, with T1D: mean age ± SD 43 ± 14 years; baseline mean HbA1c ± SD 60 mmol/mol ± 9.9 (7.6 ± 0.9%) and time in range 59.8% ± 14.8%. Participants perceived that using DIY-CGM improved both glycaemic control and aspects of quality of life. Alarm and trend functionality allowed participants to perceive reduced glycaemic variability overnight and following meals. The addition of a smartwatch increased discrete access to glucose information. There was a high degree of trust in DIY-CGM. Challenges while using DIY-CGM included signal loss during vigorous exercise, alarm fatigue and short battery life. CONCLUSIONS: This study suggests that for users, DIY-CGM appears to be an acceptable alternative method of rt-CGM.

Diabetes duration, perceived comfort with self-management and glycaemic control in adolescents with type 1 diabetes: A cross-sectional study.

AIMS: Evidence is lacking on whether diabetes duration is associated with type 1 diabetes (T1D) self-management during late adolescence before transfer from paediatric to adult care. We examined associations of diabetes duration with dimensions of perceived comfort with diabetes self-management (self-efficacy, transition readiness, diabetes distress) and glycaemic control in late adolescence. METHODS: Using a cross-sectional design, we conducted a secondary analysis of baseline data of adolescents (ages 16-17 years) with T1D followed at paediatric diabetes academic hospitals in Montreal and enrolled in the Group Education Trial to Improve Transition (GET-IT-T1D). Participants completed validated questionnaires on self-efficacy (Self-Efficacy for Diabetes Self-Management Measure [SEDM], score 1 to 10), diabetes distress and transition readiness, as well as a haemoglobin (HbA1c) capillary blood test. Our primary outcome was self-efficacy. We examined associations of diabetes duration with self-efficacy, diabetes distress, transition readiness and HbA1c using linear and logistic regression models adjusted for sex, socioeconomic status, insulin pump use, glucose sensor use and psychiatric comorbidity. RESULTS: Of 203 adolescents with T1D, mean diabetes duration (SD) was 7.57 (4.44) years. Mean SEDM score was 6.83 (SD 1.62). Diabetes duration was not associated with self-efficacy, diabetes distress or transition readiness. Each additional year of diabetes duration was associated with 0.11% (95% CI, 0.05 to 0.16) higher HbA1c. CONCLUSIONS: Although diabetes duration is not associated with dimensions of perceived comfort with diabetes self-management, adolescents with longer diabetes duration are at risk for higher HbA1c and may need additional support to improve glycaemic control before transition to adult care.

A register-based study describing time trends in risk factor control and serious hypoglycaemia together with the effects of starting continuous glucose monitoring in people with type 1 diabetes in Norway.

AIMS: To describe trends in risk factor control and serious hypoglycaemia in people with type 1 diabetes and to assess the effect of starting continuous glucose monitoring (CGM) in the real-world setting. METHODS: Two cross-sectional surveys including 5746 individuals in 2012 and 18,984 individuals in 2020 based on data recorded in the Norwegian Diabetes Register for Adults (NDR-A) and an analysis of a longitudinal cohort of 2057 individuals where data on CGM and HbA1c were available in the NDR-A in 2012 and 2020. RESULTS: In the cross-sectional surveys mean HbA1c decreased from 66 mmol/mol (99% CI 65, 66) (8.2%) in 2012 to 61 mmol/mol (99% CI 61, 61) (7.7%) in 2020 (p < 0.0001). The proportion reporting serious hypoglycaemia decreased from 16.9 to 6.2% in 2020 (p < 0.0001). Mean LDL-cholesterol decreased from 2.80 (99% CI 2.78, 2.83) to 2.63 (99% CI 2.61, 2.65) mmol/l in 2020 (p < 0.0001). Mean blood pressure increased slightly. In the CGM cohort, we found a 3 mmol/mol (0.3%) greater improvement in mean HbA1c and a greater reduction in serious hypoglycaemia (-12.3% vs. -6.2%) among individuals that had started using CGM between 2013 and 2020 when compared with individuals that had not started using CGM. CONCLUSIONS: Between 2012 and 2020, we found marked improvements in glycaemic control and a considerable decrease in the proportion of individuals reporting serious hypoglycaemia. The proportion of individuals using CGM increased substantially and individuals that had started using CGM by 2020 showed greater improvement in glycaemic control and less serious hypoglycaemia.

Strategic exploration of whole grain cereals in modulating the glycaemic response.

In the current context, diabetes presents itself as a widespread and complex global health issue. This study explores the significant influence of food microstructure and food matrix components interaction (protein, lipid, polyphenols, etc.) on the starch digestibility and the glycaemic response of post-prandial glycemia, focusing on the potential effectiveness of incorporating bioactive components from whole grain cereals into dietary strategies for the management and potential prevention of diabetes. This study aims to integrate the regulation of postprandial glycaemic homeostasis, including the complexities of starch digestion, the significant potential of bioactive whole grain components and the impact of food processing, to develop a comprehensive framework that combines these elements into a strategic approach to diabetes nutrition. The convergence of these nutritional strategies is analyzed in the context of various prevalent dietary patterns, with the objective of creating an accessible approach to mitigate and prevent diabetes. The objective remains to coalesce these nutritional paradigms into a coherent strategy that not only addresses the current public health crisis but also threads a preventative approach to mitigate future prevalence and impact.

Twenty-four-hour physical behaviour profiles across type 2 diabetes mellitus subtypes.

AIM: To investigate how 24-h physical behaviours differ across type 2 diabetes (T2DM) subtypes. MATERIALS AND METHODS: We included participants living with T2DM, enrolled as part of an ongoing observational study. Participants wore an accelerometer for 7 days to quantify physical behaviours across 24 h. We used routinely collected clinical data (age at onset of diabetes, glycated haemoglobin level, homeostatic model assessment index of beta-cell function, homeostatic model assessment index of insulin resistance, body mass index) to replicate four previously identified subtypes (insulin-deficient diabetes [INS-D], insulin-resistant diabetes [INS-R], obesity-related diabetes [OB] and age-related diabetes [AGE]), via k-means clustering. Differences in physical behaviours across the diabetes subtypes were assessed using generalized linear models, with the AGE cluster as the reference. RESULTS: A total of 564 participants were included in this analysis (mean age 63.6 ± 8.4 years, 37.6% female, mean age at diagnosis 53.1 ± 10.0 years). The proportions in each cluster were as follows: INS-D: n = 35, 6.2%; INS-R: n = 88, 15.6%; OB: n = 166, 29.4%; and AGE: n = 275, 48.8%. Compared to the AGE cluster, the OB cluster had a shorter sleep duration (-0.3 h; 95% confidence interval [CI] -0.5, -0.1), lower sleep efficiency (-2%; 95% CI -3, -1), lower total physical activity (-2.9 mg; 95% CI -4.3, -1.6) and less time in moderate-to-vigorous physical activity (-6.6 min; 95% CI -11.4, -1.7), alongside greater sleep variability (17.9 min; 95% CI 8.2, 27.7) and longer sedentary time (31.9 min; 95% CI 10.5, 53.2). Movement intensity during the most active continuous 10 and 30 min of the day was also lower in the OB cluster. CONCLUSIONS: In individuals living with T2DM, the OB subtype had the lowest levels of physical activity and least favourable sleep profiles. Such behaviours may be suitable targets for personalized therapeutic lifestyle interventions.

Metformin: Therapeutic profile in the treatment of type 2 diabetes.

Metformin (dimethyl-biguanide) can claim its origins in the use of Galega officinalis as a plant treatment for symptoms ascribed to diabetes. Since the first clinical use of metformin as a glucose-lowering agent in 1957, this medicine has emerged as a first-line pharmacological option to support lifestyle interventions in the management of type 2 diabetes (T2D). It acts through multiple cellular pathways, principally in the gut, liver and muscle, to counter insulin resistance and lower blood glucose without weight gain or risk of overt hypoglycaemia. Other effects include improvements in lipid metabolism, decreased inflammation and lower long-term cardiovascular risk. Metformin is conveniently combined with other diabetes medications, can be prescribed in prediabetes to reduce the risk of progression to T2D, and is used in some regions to assist glycaemic control in pregnancy. Consistent with its diversity of actions, established safety profile and cost-effectiveness, metformin is being assessed for further possible clinical applications. The use of metformin requires adequate renal function for drug elimination, and may cause initial gastrointestinal side effects, which can be moderated by taking with meals or using an extended-release formulation. Thus, metformin serves as a valuable therapeutic resource for use throughout the natural history of T2D.

Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

AIMS: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. RESULTS: In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). CONCLUSIONS: Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.

Could poor glycaemic control be a predictor of walking speed decline in older adults? Evidence from the English Longitudinal Study of Ageing.

AIM: Although diabetes is a risk factor for walking speed decline in older adults, it remains unclear how glycaemic control [assessed by glycated haemoglobin (HbA1c)] might affect the long-term trajectories of walking speed. We investigated whether the glycaemic control status accelerates the walking speed decline and whether this decline differs depending on previous mobility conditions. MATERIALS AND METHODS: In total, 3202 individuals aged ≥60 years from the English Longitudinal Study of Ageing (ELSA) were classified at baseline and after 4 and 8 years of follow-up according to glycaemic control status as 'without diabetes' (no self-reported diabetes and HbA1c <6.5%), 'good glycaemic control' (self-reported diabetes and HbA1c ≥6.5% and <7.0%) and 'poor glycaemic control' (PGC) (self-reported diabetes and HbA1c ≥7.0%). The generalized linear mixed models verified the walking speed trajectories in m/s. A second analysis was performed, including only participants without slowness at baseline (>0.8 m/s). RESULTS: Compared with the status 'without diabetes', the annual walking speed decline was -0.015 m/s for PGC and -0.011 m/s for good glycaemic control, totalling -0.160 and -0.130 m/s, respectively, over 8 years. Among those without slowness at baseline, only PGC had a significant walking speed decline, corresponding to -0.014 m/s per year and -0.222 m/s over 8 years. CONCLUSIONS: Poor glycaemic control is a discriminator of walking speed decline in older adults, regardless of previous mobility conditions. It may serve as an early screening tool for those at risk of decreased functional performance later in life.

Cost-utility analysis of a flash continuous glucose monitoring system in the management of people with type 2 diabetes mellitus on basal insulin therapy-An Italian healthcare system perspective.

AIMS: To assess the cost-utility of the FreeStyle Libre flash continuous glucose monitoring (CGM) system from an Italian healthcare system perspective, when compared with self-monitoring of blood glucose (SMBG) in people living with type 2 diabetes mellitus (T2DM) receiving basal insulin. MATERIALS AND METHODS: A patient-level microsimulation model was run using Microsoft Excel for 10 000 patients over a lifetime horizon, with 3.0% discounting for costs and utilities. Inputs were based on clinical trials and real-world evidence, with patient characteristics reflecting Italian population data. The effect of flash CGM was modelled as a persistent 0.8% reduction in glycated haemoglobin versus SMBG. Costs (€ 2023) and disutilities were applied to glucose monitoring, diabetes complications, severe hypoglycaemia, and diabetic ketoacidosis. The health outcome was measured as quality-adjusted life-years (QALYs). RESULTS: Direct costs were €5338 higher with flash CGM than with SMBG. Flash CGM was associated with 0.51 more QALYs than SMBG, giving an incremental cost-effectiveness ratio (ICER) of €10 556/QALY. Scenario analysis ICERs ranged from €3825/QALY to €26 737/QALY. In probabilistic analysis, flash CGM was 100% likely to be cost effective at willingness-to-pay thresholds > €20 000/QALY. CONCLUSIONS: From an Italian healthcare system perspective, flash CGM is cost effective compared with SMBG for people living with T2DM on basal insulin.

Pre-exercise protein intake is associated with reduced time in hypoglycaemia among adolescents with type 1 diabetes.

AIM: Secondary analyses were conducted from a randomized trial of an adaptive behavioural intervention to assess the relationship between protein intake (g and g/kg) consumed within 4 h before moderate-to-vigorous physical activity (MVPA) bouts and glycaemia during and following MVPA bouts among adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: Adolescents (n = 112) with T1D, 14.5 (13.8, 15.7) years of age and 36.6% overweight/obese, provided measures of glycaemia using continuous glucose monitoring [percentage of time above range (>180 mg/dl), time in range (70-180 mg/dl), time below range (TBR; <70 mg/dl)], self-reported physical activity (previous day physical activity recalls), and 24 h dietary recall data at baseline and 6 months post-intervention. Mixed effects regression models adjusted for design (randomization assignment, study site), demographic, clinical, anthropometric, dietary, physical activity and timing covariates estimated the association between pre-exercise protein intake on percentage of time above range, time in range and TBR during and following MVPA. RESULTS: Pre-exercise protein intakes of 10-19.9 g and >20 g were associated with an absolute reduction of -4.41% (p = .04) and -4.83% (p = .02) TBR during physical activity compared with those who did not consume protein before MVPA. Similarly, relative protein intakes of 0.125-0.249 g/kg and ≥0.25 g/kg were associated with -5.38% (p = .01) and -4.32% (p = .03) absolute reductions in TBR during physical activity. We did not observe a significant association between protein intake and measures of glycaemia following bouts of MVPA. CONCLUSIONS: Among adolescents with T1D, a dose of ≥10 g or ≥0.125 g/kg of protein within 4 h before MVPA may promote reduced time in hypoglycaemia during, but not following, physical activity.