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Background: Self-management education programmes are cost-effective in helping people with type 2 diabetes manage their diabetes, but referral and attendance rates are low. This study reports on the effectiveness of the Embedding Package, a programme designed to increase type 2 diabetes self-management programme attendance in primary care. Methods: Using a cluster randomised design, 66 practices were randomised to: (1) a wait-list group that provided usual care for nine months before receiving the Embedding Package for nine months, or (2) an immediate group that received the Embedding Package for 18 months. 'Embedders' supported practices and self-management programme providers to embed programme referral into routine practice, and an online 'toolkit' contained embedding support resources. Patient-level HbA1c (primary outcome), programme referral and attendance data, and clinical data from 92,977 patients with type 2 diabetes were collected at baseline (months − 3–0), step one (months 1–9), step 2 (months 10–18), and 12 months post-intervention. An integrated ethnographic study including observations, interviews, and document analysis was conducted using interpretive thematic analysis and Normalisation Process Theory. Results: No significant difference was found in HbA1c between intervention and control conditions (adjusted mean difference [95% confidence interval]: -0.10 [-0.38, 0.18] mmol/mol; -0.01 [-0.03, 0.02] %). Statistically but not clinically significantly lower levels of HbA1c were found in people of ethnic minority groups compared with non-ethnic minority groups during the intervention condition (-0.64 [-1.08, -0.20] mmol/mol; -0.06% [-0.10, -0.02], p = 0.004), but not greater self-management programme attendance. Twelve months post-intervention data showed statistically but not clinically significantly lower HbA1c (-0.56 [95% confidence interval: -0.71, -0.42] mmol/mol; -0.05 [-0.06, -0.04] %; p < 0.001), and higher self-management programme attendance (adjusted odds ratio: 1.13; 95% confidence interval: 1.02, 1.25; p = 0.017) during intervention conditions. Themes identified through the ethnographic study included challenges for Embedders in making and sustaining contact with practices and providers, and around practices' interactions with the toolkit. Conclusions: Barriers to implementing the Embedding Package may have compromised its effectiveness. Statistically but not clinically significantly improved HbA1c among ethnic minority groups and in longer-term follow-up suggest that future research exploring methods of embedding diabetes self-management programmes into routine care is warranted. Trial registration: ISRCTN23474120, registered 05/04/2018. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the use of BIAsp 30, a type of insulin, as an alternative to basal-bolus insulin regimens for people with type 2 diabetes. The study found that adding or switching to BIAsp 30 resulted in a small reduction in HbA1c levels after 6 months, along with minor changes in BMI and high treatment persistence. However, some patients still had poor glycemic control and may have needed additional treatments. The study has limitations, including potential errors and a small sample size, and was sponsored by Novo Nordisk A/S. [Extracted from the article]

OBJECTIVE: To examine the associations between age at type 2 diabetes diagnosis and the relative and absolute risk of all-cause and cause-specific mortality in England. RESEARCH DESIGN AND METHODS: In this cohort study using primary care data from the Clinical Practice Research Datalink, we identified 108,061 individuals with newly diagnosed type 2 diabetes (16–50 years of age), matched to 829,946 individuals without type 2 diabetes. We estimated all-cause and cause-specific mortality (cancer, cardiorenal, other [noncancer or cardiorenal]) by age at diagnosis, using competing-risk survival analyses adjusted for key confounders. RESULTS: Comparing individuals with versus without type 2 diabetes, the relative risk of death decreased with an older age at diagnosis: the hazard ratio for all-cause mortality was 4.32 (95% CI 3.35–5.58) in individuals diagnosed at ages 16–27 years compared with 1.53 (95% CI 1.46–1.60) at ages 48–50 years. Smaller relative risks by increasing age at diagnosis were also observed for cancer, cardiorenal, and noncancer or cardiorenal death. Irrespective of age at diagnosis, the 10-year absolute risk of all-cause and cause-specific mortality were higher in individuals with type 2 diabetes; yet, the absolute differences were small. CONCLUSIONS: Although the relative risk of death in individuals with versus without type 2 was higher at younger ages, the 10-year absolute risk of all investigated causes of death was small and similar in the two groups. Further multidecade studies could help estimate the long-term risk of complications and death in individuals with early-onset type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin‐naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England. Materials and Methods: Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin‐naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index. Results: In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %‐point changes [95% CI of −2.32 (−2.36; −2.28) (White); −1.91 (−2.02; −1.80) (South Asian); −2.55 (−2.69; −2.40) (Black); and −2.64 (−3.24; −2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m2: White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (−0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient‐years before the index to 3.37 events per 100 patient‐years post index; event numbers were too low to be analysed by subgroup. Conclusions: Among insulin‐naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between age at diagnosis of type 2 diabetes and depressive symptoms, diabetes-specific distress, and self-compassion among adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: This analysis used data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycemic Control (CODEC) cross-sectional study. Information was collected on depressive symptoms, diabetes-specific distress, and self-compassion, measured using validated self-report questionnaires, in addition to sociodemographic and clinical data. Multivariable regression models, adjusted for diabetes duration, sex, ethnicity, deprivation status, prescription of antidepressants (selective serotonin reuptake inhibitors), and BMI were used to investigate the association between age at diagnosis of type 2 diabetes and each of the three psychological outcomes. RESULTS: A total of 706 participants were included; 64 (9.1%) were diagnosed with type 2 diabetes at <40 years, 422 (59.8%) between 40 and 59 years, and 220 (31.2%) at ≥60 years of age. After adjustment for key confounders, including diabetes duration, younger age at diagnosis was significantly associated with higher levels of depressive symptoms (βadj: −0.18 [95% CI −0.25 to −0.10]; P < 0.01) and diabetes-specific distress (βadj: −0.03 [95% CI −0.04 to −0.02]; P < 0.01) and lower levels of self-compassion (βadj: 0.01 [95% CI 0.00 to 0.02]; P < 0.01). CONCLUSIONS: Diagnosis of type 2 diabetes at a younger age is associated with lower psychological well-being, suggesting the need for clinical vigilance and the availability of age-appropriate psychosocial support. [ABSTRACT FROM AUTHOR]

Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once‐weekly subcutaneous semaglutide 2.4 mg (a glucagon‐like peptide‐1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%‐17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%‐79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%‐27% with placebo) and 51%‐64% achieved ≥15% weight loss (vs. 5%‐13% with placebo). In STEP 5, mean weight loss was −15.2% with semaglutide 2.4 mg versus −2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was −9.6% with semaglutide 2.4 mg versus −3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity‐related diseases. [ABSTRACT FROM AUTHOR]

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on the management of hyperglycemia in type 2 diabetes in adults, published since 2006 and last updated in 2019. The target audience is the full spectrum of the professional health care team providing diabetes care in the U.S. and Europe. A systematic examination of publications since 2018 informed new recommendations. These include additional focus on social determinants of health, the health care system, and physical activity behaviors, including sleep. There is a greater emphasis on weight management as part of the holistic approach to diabetes management. The results of cardiovascular and kidney outcomes trials involving sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, including assessment of subgroups, inform broader recommendations for cardiorenal protection in people with diabetes at high risk of cardiorenal disease. After a summary listing of consensus recommendations, practical tips for implementation are provided. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes is a significant public health problem globally and associated with significant morbidity and mortality. Diabetes self-management education and support (DSMES) programmes are associated with improved psychological and clinical outcomes. There are currently no structured DSMES available in Ghana. We sought to adapt an evidence-based DSMES intervention for the Ghanaian population in collaboration with the local Ghanaian people.Methods: We used virtual engagements with UK-based DSMES trainers, produced locally culturally and linguistically appropriate content and modified the logistics needed for the delivery of the self-management programme to suit people with low literacy and low health literacy levels.Conclusions: A respectful understanding of the socio-cultural belief systems in Ghana as well as the peculiar challenges of low resources settings and low health literacy is necessary for adaptation of any DSMES programme for Ghana. We identified key cultural, linguistic, and logistic considerations to incorporate into a DSMES programme for Ghanaians, guided by the Ecological Validity Model. These insights can be used further to scale up availability of structured DSMES in Ghana and other low- middle- income countries. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes (T2D). Historical concerns about cardiovascular (CV) risks associated with certain glucose-lowering medications gave rise to the introduction of cardiovascular outcomes trials (CVOTs). Initially implemented to help monitor the CV safety of glucose-lowering drugs in patients with T2D, who either had established CVD or were at high risk of CVD, data that emerged from some of these trials started to show benefits. Alongside the anticipated CV safety of many of these agents, evidence for certain sodium–glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revealed potential cardioprotective effects in patients with T2D who are at high risk of CVD events. Reductions in 3-point major adverse CV events (3P-MACE) and CV death have been noted in some of these CVOTs, with additional benefits including reduced risks of hospitalisation for heart failure, progression of renal disease, and all-cause mortality. These new data are leading to a paradigm shift in the current management of T2D, with international guidelines now prioritising SGLT2 inhibitors and/or GLP-1 RAs in certain patient populations. However, clinicians are faced with a large volume of CVOT data when seeking to use this evidence base to bring opportunities to improve CV, heart failure and renal outcomes, and even reduce mortality, in their patients with T2D. The aim of this review is to provide an in-depth summary of CVOT data—crystallising the key findings, from safety to efficacy—and to offer a practical perspective for physicians. Finally, we discuss the next steps for the post-CVOT era, with ongoing studies that may further transform clinical practice and improve outcomes for people with T2D, heart failure or renal disease. [ABSTRACT FROM AUTHOR]

Aims: To assess the efficacy and safety of iGlarLixi (the titratable fixed‐ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). Materials and methods: The LixiLan‐O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan‐O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. Results: The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2‐hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c −1.9% vs. −1.6% or −1.0% [−20 vs. −17 or −10 mmol/mol; 2‐hour PPG −7.2 vs. −4.6 or −5.5 mmol/L). Greater proportions of participants achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi versus iGlar or Lixi (67% vs. 51% or 18%), and the composite endpoints of HbA1c <7% (<53 mmol/mol) with no body weight gain (36% vs. 19% or 16%), and HbA1c <7% (<53 mmol/mol) with no body weight gain and no documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L; 28% vs. 15% or 15%). The incidence rates of documented symptomatic hypoglycaemia were 29.0%, 27.9% and 12.1% for iGlarLixi, iGlar and Lixi, respectively. Conclusions: Adults with T2D and HbA1c ≥64 mmol/mol (≥8%) despite two OADs at screening achieved better glycaemic control with iGlarLixi versus iGlar or Lixi, without increased risk of hypoglycaemia versus iGlar. [ABSTRACT FROM AUTHOR]

Background: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown.Methods: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks.Results: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide.Conclusions: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.). [ABSTRACT FROM AUTHOR]

Background: Trimethylamine N-oxide (TMAO), a metabolite generated by the gut in response (in part) to meat consumption, is linked to poor cardiometabolic health.Objectives: We investigate the effect of an 8-week vegan diet, followed by a 4-week period of unrestricted diet, on glucose tolerance and plasma TMAO in human omnivores with obesity or dysglycemia.Methods: This interventional single-group prospective trial involved 23 regular meat eaters with dysglycemia [glycated hemoglobin ≥ 5.7% and ≤8% (39-64 mmol/mol)], or obesity (ΒΜΙ ≥ 30 kg/m2) aged 57.8 ± 10.0 years. Participants [14 men (60.9%) and 9 women (39.1%)] were supported in following a vegan diet for 8 weeks, followed by 4 weeks of unrestricted diet. The primary outcomes (plasma TMAO and glucose) were assessed at baseline, during the vegan diet (weeks 1 and 8), and after the unrestricted diet period (week 12). TMAO was assessed after fasting and glucose was measured as a time-averaged total AUC using a 180-minute oral-glucose-tolerance test. Generalized estimating equation models with an exchangeable correlation structure were used to assess changes from baseline, adjusting for age, sex, ethnicity, and weight.Results: TMAO levels (marginal mean) were reduced after weeks 1 and 8 of a vegan diet compared to baseline, from 10.7 (97.5% CI, 6.61-17.3) μmol/L to 5.66 (97.5% CI, 4.56-7.02) μmol/L and 6.38 (97.5% CI, 5.25-7.74) μmol/L, respectively; however, levels rebounded at week 12 after resumption of an unrestricted diet (17.5 μmol/L; 97.5% CI, 7.98-38.4). Postprandial glucose levels (marginal means) were reduced after weeks 1 and 8 compared to baseline, from 8.07 (97.5% CI, 7.24-8.90) mmol/L to 7.14 (97.5% CI, 6.30-7.98) mmol/L and 7.34 (97.5% CI, 6.63-8.04) mmol/L, respectively. Results for glucose and TMAO were independent of weight loss. Improvements in the lipid profile and markers of renal function were observed at week 8.Conclusions: These findings suggest that a vegan diet is an effective strategy for improving glucose tolerance and reducing plasma TMAO in individuals with dysglycemia or obesity. This study was registered at clinicaltrials.gov as NCT03315988. [ABSTRACT FROM AUTHOR]

Despite growing awareness of the dangers of a dichotomous interpretation of trial results based on the 'statistical significance' of a treatment effect, the uptake of new approaches has been slow in diabetes medicine. We showcase a number of ways to interpret the evidence for a treatment effect applied to the cardiovascular outcome trials of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is): the P value function (or confidence curves), which depicts the treatment effect across the whole spectrum of confidence levels; the counternull value, which is the hazard ratio (i.e. treatment effect size) supported by the same amount of evidence as the null value (i.e. no treatment effect); and the S value, which quantifies the strength of the evidence against the null hypothesis in terms of the number of coin tosses yielding the same side. We show how this approach identifies potential treatment effects, highlights similarities among trials straddling the threshold of statistical significance, and quantifies differences in the strength of the evidence from trials reporting statistically significant results. For example, while REWIND, CANVAS and CREDENCE failed to reach statistical significance at the.05 level for all‐cause mortality, their counternull values indicate that reduced death rates by 19%, 24% and 31%, respectively, are supported by the same amount of evidence as that indicating no treatment effect. Moreover, similarities among results emerge in trials of GLP‐1RAs (REWIND, EXSCEL and LEADER) lying closely around the threshold of 'statistical significance'. Lastly, several S values, such as for the primary outcome in HARMONY Outcomes (S value 10.9) and all‐cause death in EMPAREG‐OUTCOME (S value 15.0), stand out compared with values for other outcomes and other trials, suggesting much larger differences in the evidence between these studies and several others that cluster around the.05 significance threshold. P value functions, counternull values and S values should complement the standard reporting of the treatment effect to help interpret clinical trials and make decisions among competing glucose‐lowering medications. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of different categories of baseline cardio‐metabolic risk factors on the treatment effects of empagliflozin 10 and 25 mg when added as second‐line therapy to metformin in patients with type 2 diabetes (T2D). Materials and Methods: Patients aged 18 years or older with HbA1c 7.0%‐10.0% were included. Analysis of covariance compared change from baseline to weeks 24 and 76 in HbA1c, body weight (BW) and systolic blood pressure (SBP) by respective baseline categories (HbA1c <8.5/≥8.5%; BW <80/80‐90/>90 kg, SBP <130/130‐140/>140 mmHg). Analyses were also conducted with a model using continuous covariates of cardio‐metabolic factors. Results: In total, 637 patients (56.7% males; mean [SD] age 55.7 [9.9] years, HbA1c 7.9% [0.9%], BW 81.2 [18.8] kg, SBP 129.4 [14.6] mmHg) received one or more dose of either empagliflozin 10 mg (n = 217) or 25 mg (n = 213), or placebo (n = 207). At both time points, empagliflozin 10/25 mg versus placebo significantly (P <.0001) reduced HbA1c and BW, with greater reductions in HbA1c at higher baseline HbA1c (P interaction week 24/76 categorical and continuous models:.0290/.1431 and.0004/.0042, respectively) and in BW (P interaction.1340/.0012 and.0202/<.0001, respectively). Both empagliflozin doses also significantly lowered SBP versus placebo at both time points, with similar efficacy by subgroups of baseline SBP. Adverse events were consistent with the established empagliflozin safety profile across treatment groups. Conclusions: Empagliflozin, as add‐on to metformin, decreases HbA1c and BW, particularly in patients with higher HbA1c and BW baseline values, and effectively lowers SBP. [ABSTRACT FROM AUTHOR]

Cardiovascular outcome trials (CVOTs) investigating the safety and efficacy of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have highlighted some important differences among these medications. The recent American Diabetes Association and European Association for the Study of Diabetes consensus underlines that each trial constitutes a single experiment; therefore, it remains unclear if, and to what extent, the observed differences reflect the heterogeneous pharmacological properties of each compound. To help clarify the evidence, in this systematic review we investigated differences in trial characteristics which may have had an impact on the primary and secondary trial results, including baseline control of risk factors, prevalence of cardiovascular diseases, absolute rates of events, duration of the study, and definitions of the inclusion criteria and outcomes. Aiming at enhancing the clinical interpretation of these CVOTs, we quantified the absolute treatment effect over time in terms of the number needed to treat to avoid one major adverse cardiovascular event, showing variations among GLP‐1RAs. [ABSTRACT FROM AUTHOR]

The restricted mean survival time (RMST) has been advocated as an alternative or a supplement to the hazard ratio for reporting the effect of an intervention in a randomized clinical trial. The RMST difference allows quantification of the postponement of an outcome during a specified (restricted) interval and corresponds to the difference between the areas under the 2 survival curves for the intervention and control groups. This article presents examples of the use of the RMST in a research and a clinical context. First, the authors demonstrate how the RMST difference can answer research questions about the efficacy of different treatments. Estimates are presented for the effects of pharmacologic or strategy-driven glucose-lowering interventions for adults with type 2 diabetes from 36 trials and 9 follow-up studies reporting cardiovascular outcomes and mortality. The authors show how these measures may be used to mitigate uncertainty about the efficacy of intensive glucose control. Second, the authors demonstrate how the RMST difference may be used in the setting of a clinical consultation to guide the decision to start or discontinue a treatment. They then discuss the advantages of the RMST over the absolute risk difference, the number needed to treat, and the median survival time difference. They argue that the RMST difference is both easy to interpret and flexible in its application to different settings. Finally, they highlight the major limitations of the RMST, including difficulties in comparing studies of heterogeneous designs and in inferring the long-term effects of treatments using trials of short duration, and summarize the available statistical software for calculating the RMST. [ABSTRACT FROM AUTHOR]

The last decade has witnessed an exponential growth in the opportunities to collect and link health‐related data from multiple resources, including primary care, administrative, and device data. The availability of these "real‐world," "big data" has fuelled also an intense methodological research into methods to handle them and extract actionable information. In medicine, the evidence generated from "real‐world data" (RWD), which are not purposely collected to answer biomedical questions, is commonly termed "real‐world evidence" (RWE). In this review, we focus on RWD and RWE in the area of diabetes research, highlighting their contributions in the last decade; and give some suggestions for future RWE diabetes research, by applying well‐established and less‐known tools to direct RWE diabetes research towards better personalized approaches to diabetes care. We underline the essential aspects to consider when using RWD and the key features limiting the translational potential of RWD in generating high‐quality and applicable RWE. Only if viewed in the context of other study designs and statistical methods, with its pros and cons carefully considered, RWE will exploit its full potential as a complementary or even, in some cases, substitutive source of evidence compared to the expensive evidence obtained from randomized controlled trials. [ABSTRACT FROM AUTHOR]

The last decade has witnessed an exponential growth in the opportunities to collect and link health‐related data from multiple resources, including primary care, administrative, and device data. The availability of these "real‐world," "big data" has fuelled also an intense methodological research into methods to handle them and extract actionable information. In medicine, the evidence generated from "real‐world data" (RWD), which are not purposely collected to answer biomedical questions, is commonly termed "real‐world evidence" (RWE). In this review, we focus on RWD and RWE in the area of diabetes research, highlighting their contributions in the last decade; and give some suggestions for future RWE diabetes research, by applying well‐established and less‐known tools to direct RWE diabetes research towards better personalized approaches to diabetes care. We underline the essential aspects to consider when using RWD and the key features limiting the translational potential of RWD in generating high‐quality and applicable RWE. Only if viewed in the context of other study designs and statistical methods, with its pros and cons carefully considered, RWE will exploit its full potential as a complementary or even, in some cases, substitutive source of evidence compared to the expensive evidence obtained from randomized controlled trials. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of the Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) program on patient activation in adults living with type 2 diabetes (T2D).Methods: 233 individuals attended a DESMOND program in 26 locations across regional Western Australia. Individuals completed the Patient Activation Measure (PAM) prior to and immediately after DESMOND participation.Results: Patient Activation significantly increased by 9.7 points from pre to post DESMOND intervention (p < 0.001, z = -7.94). Of all participants who exhibited an increase in patient activation, 87% (n = 142) experienced a clinically significant (>5 point) increase. Post-DESMOND participation, an 86% reduction (from 6% -0.9%) in the proportion of participants scoring in the lowest PAM level (Level 1) was observed (p < 0.01).Conclusion: DESMOND, a structured diabetes self-management education (DSME) program aimed at strengthening the role of people living with type 2 diabetes in self-managing their healthcare, significantly increased patient activation in a real-world setting.Practice Implications: In line with international diabetes guidelines it is recommended that people living with T2D, particularly those with lower levels of activation, attend an evidence based DSME such as DESMOND to increase their capacity to effectively self-manage their condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide's effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1] and A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS: At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (−2.6% vs. −2.4%), BW (−14 vs. −13 kg), WC (−10 vs. −10 cm), triglycerides (−26% vs. −24%), HDL (7% vs. 7%), and systolic BP (−6 vs. −7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D. [ABSTRACT FROM AUTHOR]

In this post hoc analysis of the randomized controlled LixiLan‐O trial in insulin‐naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed‐ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs. [ABSTRACT FROM AUTHOR]

Background & Aims: A causal association of non‐alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and type 2 diabetes (T2DM) remains unproved. We aimed to quantify the likelihood of causality examining the sensitivity of observational associations to possible confounding. Methods: Studies investigating longitudinal associations of NAFLD with CVD or T2DM were searched on 5 June 2018. Study‐specific relative risks (RRs) were combined in random‐effects meta‐analyses and pooled estimates used in bias analyses. Results: Associations of NAFLD with CVD and T2DM were reported in 13 (258 743/18 383 participants/events) and 20 (240 251/12 891) studies respectively. Comparing patients with NAFLD to those without, the pooled RR was 1.48 (95% CI: 0.96, 2.29) for CVD and 2.17 (1.77, 2.65) for T2DM. In bias analyses, for an unmeasured confounder associated to both NAFLD and CVD with a RR of 1.25, the proportion of studies with a true (causal) effect of NAFLD on CVD surpassing a RR of 1.10 (ie, 10% increased risk of CVD in participants with NAFLD) was 0.67 (95% CI: 0.42, 0.92) while for 75% increase, it was 0.36 (0.11, 0.62). Corresponding figures for T2DM were 0.97 (0.91, 1.00) for a 10% increased risk of T2DM in participants with NAFLD to 0.70 (0.49, 0.92) for a 75% increase. Conclusions: The results of this study are strongly suggestive for a causal relationship between NAFLD and T2DM, while the evidence for a causal link between NAFLD and CVD is less robust. Therapeutic strategies targeting NAFLD are likely to reduce the risk of developing T2DM. [ABSTRACT FROM AUTHOR]

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: This study aimed to determine the cross-sectional and cumulative compliance of adolescent girls to accelerometer wear at three deployment points and to identify variables associated with compliance. Methods: Girls from 20 secondary schools were recruited: 10 schools were participating in the “Girls Active” intervention and 10 were control schools. Physical activity was measured using the GENEActiv accelerometer worn on the nondominant wrist 24 h·d−1 for up to 7 d at baseline, 7 months, and 14 months. Demographic and anthropometric characteristics were recorded. Results: Seven valid days (≥16 h) of accelerometer wear was obtained from 83%, 77%, and 68% of girls at baseline (n = 1734), 7 months (n = 1381), and 14 months (n = 1326), respectively. Sixty-eight percent provided 7 valid days for both baseline and 7 months, 59% for baseline and 14 months, and 52% for all three deployment points. Estimates of physical activity level from 3 d of measurement could be considered equivalent to a 7-d measure (i.e., they fell within a ±5% equivalence zone). Cross sectionally, 3 valid days was obtained from at least 91% of girls; cumulatively, this was obtained from ≥88% of girls across any two deployment points and 84% of girls across all three deployment points. When controlling for clustering at school level and other potential predictors, physical activity level, being South Asian, being in the intervention group, and prior compliance were positively associated with monitor wear. Conclusions: Compliance reduced across deployment points, with the reduction increasing as the deployment points got further apart. High prior compliance and high physical activity level were associated with the most additional wear time. [ABSTRACT FROM AUTHOR]

The incretin therapies glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) and dipeptidyl peptidase‐IV (DPP‐IV) inhibitors are now well‐established as second and third‐line therapies and in combination with insulin for the treatment of type 2 diabetes. Over the last decade, there is accumulating evidence of their efficacy and safety from both large multicentre randomized clinical trials (RCT) and observational studies. Cardiovascular outcome trials have confirmed that several of these agents are also non‐inferior to placebo with the GLP‐1 RA liraglutide and semaglutide recently found to be superior in terms of major adverse cardiovascular events. Observational studies and post‐marketing surveillance provide real world evidence of safety and effectiveness of these agents and have provided reassurance that signals for pancreatitis and pancreatic cancer seen in clinical trials are not of major concern in large patient populations. Well‐designed real world studies complement RCTs and systematic reviews but appropriate data and methodologies, which are constantly improving, are necessary to answer appropriate clinical questions relating to the use of incretin therapies. [ABSTRACT FROM AUTHOR]

To determine whether baseline characteristics had an impact on clinical outcomes in the LixiLan-O trial (N = 1170), we compared the efficacy and safety of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U ( iGlar) and lixisenatide (Lixi) with iGlar or Lixi alone in patients with uncontrolled type 2 diabetes mellitus ( T2DM) on oral therapy. Subgroups according to baseline glycated haemoglobin ( HbA1c; <8% or ≥8% [<64 or ≥64 mmol/mol]), T2DM disease duration (<7 or ≥7 years) and body mass index ( BMI; <30 or ≥30 kg/m2) were investigated. In all subpopulations, iGlarLixi was consistently statistically superior to iGlar and Lixi alone in reducing HbA1c from baseline to week 30; higher proportions of patients achieved HbA1c <7% (<53 mmol/mol) with iGlarLixi vs iGlar and Lixi alone. Compared with iGlar, iGlarLixi resulted in a substantial decrease in 2-hour postprandial plasma glucose levels, and mitigation of weight gain, with no differences among subpopulations in incidence of symptomatic hypoglycaemia. iGlarLixi consistently improved glycaemic control compared with iGlar and Lixi alone, without weight gain or increase in hypoglycaemic risk compared with iGlar in the subpopulations tested, regardless of baseline HbA1c, disease duration and BMI. [ABSTRACT FROM AUTHOR]

Aims: To quantify whether insulin therapy, and concomitant weight gain, affects recreational physical activity and TV viewing time using data from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial.Methods: 12,537 insulin-naïve individuals with dysglycaemia were randomised to receive either basal insulin glargine or standard care and followed for a median of 6.2years. Complete recreational physical activity and TV viewing time questionnaires across baseline, 2year follow-up and study end were available for 8954 participants. Differences between groups at follow-up were assessed by analysis of covariance.Results: At follow-up, there was no difference in physical activity or TV viewing time between those taking insulin glargine and those receiving standard care, despite body weight increasing by 1.66 (7.56) kg in the insulin glargine group and reducing by -0.65 (7.90) kg in the standard care group (P<0.001). The dose of insulin glargine was not associated with changes in physical activity.Conclusions: Despite modest weight gain, insulin glargine did not adversely impact recreational physical activity levels within an international cohort with dysglyaemia. ORIGIN ClinicalTrials.gov number: NCT00069784. [ABSTRACT FROM AUTHOR]

Aims: Weight loss-induced serum creatinine reduction may increase creatinine-based estimated glomerular filtration rate (eGFR) producing incorrect estimates of kidney function. We investigated whether weight changes in the SCALE program with liraglutide 3.0mg were associated with changes in serum creatinine.Methods: Post hoc analysis of two 56-week, randomized, double-blind trials: SCALE Obesity and Prediabetes (n=3731, without type 2 diabetes [T2D], randomized [2:1] to liraglutide 3.0mg [n=2487] or placebo [n=1244]); SCALE Diabetes (n=846 with T2D, randomized [2:1:1] to liraglutide 3.0mg [n=423], 1.8mg [n=211, excluded from this analysis] or placebo [n=212]). NCT01272219/NCT01272232.Results: In SCALE Obesity and Prediabetes, mean (±SD) weight loss (baseline to week 56) with liraglutide was 8.0±6.7% (2.6±6.9% with placebo); baseline creatinine with liraglutide was 76±15μmol/L and 74±15μmol/L after 56weeks (similar across treatment groups). In SCALE Diabetes, weight loss with liraglutide was 5.9±5.5% (2.0±4.3% with placebo); baseline creatinine was 79±19μmol/L (77±16μmol/L, placebo) and 79±20μmol/L after 56weeks (76±15μmol/L, placebo). No association between changes in weight and changes in serum creatinine was observed (P≥0.05, both trials, all tests).Conclusions: Moderate gradual body weight reductions observed in the SCALE program were not associated with changes in serum creatinine. [ABSTRACT FROM AUTHOR]

Objectives: Prevention of type 2 diabetes (T2DM) is a priority in healthcare, but there is a lack of evidence investigating how to effectively translate prevention research into a UK primary care setting. We assessed whether a structured education programme targeting lifestyle and behaviour change was effective at preventing progression to T2DM in people with pre-diabetes.Materials and Methods: Forty-four general practices were randomised to receive either standard care or a 6hour group structured education programme with an annual refresher course, and regular phone contact. Participants were followed up for 3years. The primary outcome was progression to T2DM.Results: Eight hundred and eighty participants were included (36% female, mean age 64years, 16% ethnic minority group); 131 participants developed T2DM. There was a non-significant 26% reduced risk of developing T2DM in the intervention arm compared to standard care (HR 0.74, 95% CI 0.48, 1.14, p=0.18). The reduction in T2DM risk when excluding those who did not attend the initial education session was also non-significant (HR 0.65, 0.41, 1.03, p=0.07). There were statistically significant improvements in HbA1c (-0.06, -0.11, -0.01), LDL cholesterol (-0.08, -0.15, -0.01), sedentary time (-26.29, -45.26, -7.32) and step count (498.15, 162.10, 834.20) when data were analysed across all time points.Conclusions: This study suggests that a relatively low resource, pragmatic diabetes prevention programme resulted in modest benefits to biomedical, lifestyle and psychosocial outcomes, however the reduction to the risk of T2DM did not reach significance. The findings have important implications for future research and primary care. [ABSTRACT FROM AUTHOR]

Objective: Renal impairment in type 2 diabetes limits available glucose-lowering treatment options. This trial was conducted to establish the efficacy and safety of liraglutide as an add-on to existing glucose-lowering medications in patients with inadequately controlled type 2 diabetes and moderate renal impairment.Research Design and Methods: In this 26-week, double-blind trial, 279 patients with HbA1c 7-10%, BMI 20-45 kg/m(2), and moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-59 mL/min/1.73 m(2); MDRD) were randomized (1:1) to once-daily liraglutide 1.8 mg (n = 140) or placebo (n = 139).Results: The estimated treatment difference in HbA1c from baseline to week 26 was -0.66% (-7.25 mmol/mol) (95% CI -0.90 to -0.43 [-9.82 to -4.69]), P < 0.0001). Fasting plasma glucose decreased more with liraglutide (-1.22 mmol/L [-22.0 mg/dL]) than with placebo (-0.57 mmol/L [-10.3 mg/dL], P = 0.036). There was a greater reduction in body weight with liraglutide (-2.41 kg) than with placebo (-1.09 kg, P = 0.0052). No changes in renal function were observed (eGFR relative ratio to baseline: -1% liraglutide, +1% placebo; estimated treatment ratio [ETR] 0.98, P = 0.36). The most common adverse events were gastrointestinal (GI) adverse effects (liraglutide, 35.7%; placebo, 17.5%). No difference in hypoglycemic episodes was observed between treatment groups (event rate/100 patient-years of exposure: liraglutide, 30.47; placebo, 40.08; P = 0.54). The estimated ratio to baseline for lipase was 1.33 for liraglutide and 0.97 for placebo (ETR 1.37, P < 0.0001).Conclusions: Liraglutide did not affect renal function and demonstrated better glycemic control, with no increase in hypoglycemia risk but with higher withdrawals due to GI adverse events than placebo in patients with type 2 diabetes and moderate renal impairment. [ABSTRACT FROM AUTHOR]

Objective: To determine whether breaking up prolonged sitting with short bouts of standing or walking improves postprandial markers of cardiometabolic health in women at high risk of type 2 diabetes.Research Design and Methods: Twenty-two overweight/obese, dysglycemic, postmenopausal women (mean ± SD age 66.6 ± 4.7 years) each participated in two of the following treatments: prolonged, unbroken sitting (7.5 h) or prolonged sitting broken up with either standing or walking at a self-perceived light intensity (for 5 min every 30 min). Both allocation and treatment order were randomized. The incremental area under the curves (iAUCs) for glucose, insulin, nonesterified fatty acids (NEFA), and triglycerides were calculated for each treatment condition (mean ± SEM). The following day, all participants underwent the 7.5-h sitting protocol.Results: Compared with a prolonged bout of sitting (iAUC 5.3 ± 0.8 mmol/L ⋅ h), both standing (3.5 ± 0.8 mmol/L ⋅ h) and walking (3.8 ± 0.7 mmol/L ⋅ h) significantly reduced the glucose iAUC (both P < 0.05). When compared with prolonged sitting (548.2 ± 71.8 mU/L ⋅ h), insulin was also reduced for both activity conditions (standing, 437.2 ± 73.5 mU/L ⋅ h; walking, 347.9 ± 78.7 mU/L ⋅ h; both P < 0.05). Both standing (-1.0 ± 0.2 mmol/L ⋅ h) and walking (-0.8 ± 0.2 mmol/L ⋅ h) attenuated the suppression of NEFA compared with prolonged sitting (-1.5 ± 0.2 mmol/L ⋅ h) (both P < 0.05). There was no significant effect on triglyceride iAUC. The effects on glucose (standing and walking) and insulin (walking only) persisted into the following day.Conclusions: Breaking up prolonged sitting with 5-min bouts of standing or walking at a self-perceived light intensity reduced postprandial glucose, insulin, and NEFA responses in women at high risk of type 2 diabetes. This simple, behavioral approach could inform future public health interventions aimed at improving the metabolic profile of postmenopausal, dysglycemic women. [ABSTRACT FROM AUTHOR]

Background: Home foot temperature monitoring (HFTM) is recommended for those at moderate to high ulcer risk. Where a > 2.2°C difference in temperature between feet (hotspot) is detected, it is suggested that individuals (1) notify a healthcare professional (HCP); (2) reduce daily steps by 50%. We assess adherence to this and HFTM upon detecting a recurrent hotspot. Methods: PubMed and Google Scholar were searched until 9 June 2023 for English‐language peer‐reviewed HFTM studies which reported adherence to HFTM, daily step reduction or HCP hotspot notification. The search returned 1030 results excluding duplicates of which 28 were shortlisted and 11 included. Results: Typical adherence among HFTM study participants for >3 days per week was 61%–93% or >80% of study duration was 55.6%–83.1%. Monitoring foot temperatures >50% of the study duration was associated with decreased ulcer risk (Odds Ratio: 0.50, p < 0.001) in one study (n = 173), but no additional risk reduction was found for >80% adherence. Voluntary dropout was 5.2% (Smart mats); 8.1% (sock sensor) and 4.8%–35.8% (infrared thermometers). Only 16.9%–52.5% of participants notified an HCP upon hotspot detection. Objective evidence of adherence to 50% reduction in daily steps upon hotspot detection was limited to one study where the average step reduction was a pedometer‐measured 51.2%. Conclusions: Ulcer risk reduction through HFTM is poorly understood given only half of the participants notify HCPs of recurrent hotspots and the number of reducing daily steps is largely unknown. HFTM adherence and dropout are variable and more research is needed to determine factors affecting adherence and those likely to adhere. [ABSTRACT FROM AUTHOR]

The last 90 years have seen considerable advances in the management of type 1 and type 2 diabetes. Prof MacLean of Guy's Hospital wrote in the Postgraduate Medical Journal in 1926 about the numerous challenges that faced patients and their healthcare professionals in delivering safe and effective diabetes care at that time. The discovery of insulin in 1922 heralded a new age in enabling long-term glycaemic control, which reduced morbidity and mortality. Thirty years later, the first oral agents for diabetes, the biguanides and sulfonylureas, appeared and freed type 2 patients from having to inject insulin following diagnosis. Improvements in insulin formulations over the decades, including rapid-acting and long-acting insulin analogues that more closely mimic physiological insulin secretion, have increased the flexibility and efficacy of type 1 diabetes management. The last two decades have seen major advances in technology, which has manifested in more accurate glucose monitoring systems and insulin delivery devices ('insulin pump'). Increased understanding of the pathophysiological deficits underlying type 2 diabetes has led to the development of targeted therapeutic approaches such as on the small intestine (glucagon-like peptide-1 receptor analogues and dipeptidyl-peptidase IV inhibitors) and kidneys (sodium-glucose cotransporter-2 inhibitors). A patient-centred approach delivered by a multidisciplinary team is now advocated. Glycaemic targets are set according to individual circumstances, taking into account factors such as weight, hypoglycaemia risk and patient preference. Stepwise treatment guidelines devised by international diabetes organisations standardise and rationalise management. Structured education programmes and psychological support are now well-established as essential for improving patient motivation and self-empowerment. Large multicentre randomised trials have confirmed the effectiveness of intensive glycaemic control on microvascular outcomes, but macrovascular outcomes and cardiovascular safety remain controversial with several glucose-lowering agents. Future directions in diabetes care include strategies such as the 'bionic pancreas', stem cell therapy and targeting the intestinal microbiome. All of these treatments are still being refined, and it may be several decades before they are clinically useful. Prevention and cure of diabetes is the Holy Grail but remain elusive due to lack of detailed understanding of the metabolic, genetic and immunological causes that underpin diabetes. Much progress has been made since the time of Prof MacLean 90 years ago, but there are still great strides to be taken before the life of the patient with diabetes improves even more significantly. [ABSTRACT FROM AUTHOR]

Objective To understand the phenotypic presentation of women with polycystic ovary syndrome ( PCOS) of different ethnicities and at different ages. Design Cross-sectional, retrospective data analysis (1988 - 2009). Setting Specialist clinic in a University Hospital, Leicestershire, UK. Participants Women with PCOS, n = 1310 (mean age 26·2 years), 70·9% White and 29·1% South Asian ( SA) attending a speciality clinic in Leicester UK. Main Outcomes measures Clinical and demographic characteristics of women with PCOS including age at first clinic appointment, signs and symptoms, body mass index ( BMI) and blood pressure ( BP). Results Compared to White women, the SA were younger (24·3 vs 27·1 years, P < 0·001), less likely to smoke (3·7% vs 17·9% P < 0·001) and had a higher prevalence of acanthosis nigricans ( AN) (16·8% vs 3·1% P < 0·001), type 2 diabetes (T2 DM) (8·1% vs 5·6%, P < 0·01) and hirsutism (88·5% vs 77·4%, P < 0·001), with lower systolic (126·5 vs 133·0 mmHg, P < 0·001), diastolic BP (71·8 vs 75·1 mmHg P = 0·008) and BMI (29·3 vs 31·5 kg/m2 P = 0·002). Differences in body weight remained when participants were classified as obese, overweight and normal according to ethnicity-specific cut-off points ( P = 0·048). In both ethnicities, those aged ≥30 years old had higher rates of obesity, T2 DM, hypertension and infertility, and less acne, and oligomenorrhoea. Obesity was associated with increased T2 DM, AN, systolic/diastolic BP, hirsutism and infertility. Conclusion The phenotypic and metabolic presentations of women with PCOS appear to be significantly different depending on ethnicity, obesity and age. This has implications for management strategies in these groups. [ABSTRACT FROM AUTHOR]

Objective: Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, enhances urinary glucose excretion through an insulin-independent mode of action, and improves glycemic control in patients with type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of canagliflozin across racial groups.Methods: The efficacy of canagliflozin 100 mg and 300 mg was evaluated by racial group using data pooled from four placebo-controlled phase 3 studies and two placebo-controlled sub-studies of a population of patients with inadequately controlled T2DM (N = 4158). Least-squares mean changes from baseline were calculated for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), body weight (BW), cholesterol, and triglycerides. Safety/tolerability evaluation included reporting of general and prespecified adverse events (AEs).Results: A total of 75% of patients were White, 13% were Asian, 4% were Black/African American, and 8% were 'Other' (American Indian, Alaskan Native, mixed race, Native Hawaiian or other Pacific Islander, not reported, and unknown). Baseline demographics were similar for these groups. Dose-related reductions in HbA1c, BW, and SBP were observed with both canagliflozin doses in all racial groups. Canagliflozin was generally safe and well tolerated. Treatment with canagliflozin was associated with an increased rate of genital mycotic infections (GMIs) and urinary tract infections (UTIs) in all racial groups. GMIs were observed more often in Black/African American males and males from the 'Other' racial group, whereas UTIs and osmotic diuresis-related AEs were less common in Asians. Key study limitations include the high proportion of White patients compared with other racial groups and the fact that included studies were not powered to evaluate racial differences.Conclusion: Canagliflozin was generally well tolerated and consistently associated with reductions in HbA1c, BW, and SBP in patients with T2DM independent of racial background. (ClinicalTrials.gov numbers: NCT01081834; NCT01106677; NCT01106625; NCT01106690; and NCT01032629.). [ABSTRACT FROM AUTHOR]

Importance: Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available.Objective: To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes.Design, Setting, and Participants: Fifty-six-week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%.Interventions: Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (≥150 min/wk).Main Outcomes and Measures: Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56.Results: Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, -4.00% [95% CI, -5.10% to -2.90%]; liraglutide [1.8 mg] vs placebo, -2.71% [95% CI, -4.00% to -1.42%]; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 32.9% [95% CI, 24.6% to 41.2%]; for liraglutide [1.8 mg] vs placebo, 19.0% [95% CI, 9.1% to 28.8%]; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 18.5% [95% CI, 12.7% to 24.4%], P < .001; for liraglutide [1.8 mg] vs placebo, 9.3% [95% CI, 2.7% to 15.8%], P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported.Conclusions and Relevance: Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety.Trial Registration: clinicaltrials.gov Identifier:NCT01272232. [ABSTRACT FROM AUTHOR]

IMPORTANCE Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available. OBJECTIVE To investigate efficacy and safety of liraglutide vs placebo for weight management in adults with overweight or obesity and type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Fifty-six–week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%. INTERVENTIONS Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (≥150 min/wk). MAIN OUTCOMES AND MEASURES Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56. RESULTS Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, −4.00% [95% CI, −5.10% to −2.90%]; liraglutide [1.8 mg] vs placebo, −2.71% [95% CI, −4.00% to −1.42%]; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 32.9% [95% CI, 24.6% to 41.2%]; for liraglutide [1.8 mg] vs placebo, 19.0% [95% CI, 9.1% to 28.8%]; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide [3.0 mg] vs placebo, 18.5% [95% CI, 12.7% to 24.4%], P < .001; for liraglutide [1.8 mg] vs placebo, 9.3% [95% CI, 2.7% to 15.8%], P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported. CONCLUSIONS AND RELEVANCE Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Peroxisome proliferator-activated receptor gamma (PPARγ) is an important regulator of metabolic health and a common polymorphism in the PPAR-γ2 gene (PPARG2) may modify associations between lifestyle behaviour and health. Objective: To investigate whether the PPARG2 Pro12Ala genotype modifies the associations of sedentary behaviour and moderate-to-vigorous intensity physical activity (MVPA) with common measures of insulin sensitivity. Methods: Participants with a high risk of impaired glucose regulation were recruited, United Kingdom, 2010-2011. Sedentary and MVPA time were objectively measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated using Matsuda-ISI and HOMA-IS. DNA was extracted from whole blood. Linear regression examined associations of sedentary time and MVPA with insulin sensitivity and examined interactions by PPARG2 Pro12Ala genotype. Results: 541 subjects were included (average age = 65 years, female = 33%); 18% carried the Ala12 allele. Both sedentary time and MVPA were strongly associated with HOMA-IS and Matsuda-ISI after adjustment for age, sex, ethnicity, medication, smoking status and accelerometer wear time. After further adjustment for each other and BMI, only associations with Matsuda-ISI were maintained. Every 30 minute difference in sedentary time was inversely associated with a 4% (0, 8%; p = 0.043) difference in Matsuda-ISI, whereas every 30 minutes in MVPA was positively associated with a 13% (0, 26%; p = 0.048) difference. The association of MVPA with Matsuda-ISI was modified by genotype (p = 0.005) and only maintained in Ala12 allele carriers. Conversely, sedentary time was not modified by genotype and remained inversely associated with insulin sensitivity in Pro12 allele homozygotes. Conclusion: The association of MVPA with Matsuda-ISI was modified by PPARG2 Pro12Ala genotype with significant associations only observed in the 18% of the population who carried the Ala12 allele, whereas associations with sedentary time were unaffected. [ABSTRACT FROM AUTHOR]

Cardiometabolic conditions, including type 1 and type 2 diabetes mellitus, are associated with severe COVID-19 and long COVID. Interventions to target multiple risk factors, combined with use of novel glucose-lowering agents that improve metabolic function and the key processes that are impaired in COVID-19, should be the preferred therapeutic options for management of people with long COVID. [ABSTRACT FROM AUTHOR]

Summary: To evaluate the criterion validity of an automated sleep detection algorithm applied to data from three research‐grade accelerometers worn on each wrist with concurrent laboratory‐based polysomnography (PSG). A total of 30 healthy volunteers (mean [SD] age 31.5 [7.2] years, body mass index 25.5 [3.7] kg/m2) wore an Axivity, GENEActiv and ActiGraph accelerometer on each wrist during a 1‐night PSG assessment. Sleep estimates (sleep period time window [SPT‐window], sleep duration, sleep onset and waking time, sleep efficiency, and wake after sleep onset [WASO]) were generated using the automated sleep detection algorithm within the open‐source GGIR package. Agreement of sleep estimates from accelerometer data with PSG was determined using pairwise 95% equivalence tests (±10% equivalence zone), intraclass correlation coefficients (ICCs) with 95% confidence intervals and limits of agreement (LoA). Accelerometer‐derived sleep estimates except for WASO were within the 10% equivalence zone of the PSG. Reliability between data from the accelerometers worn on either wrist and PSG was moderate for SPT‐window duration (ICCs ≥ 0.65), sleep duration (ICCs ≥ 0.54), and sleep onset (ICCs ≥ 0.61), mostly good for waking time (ICCs ≥ 0.80), but poor for sleep efficiency (ICCs ≥ 0.08) and WASO (ICCs ≥ 0.08). The mean bias between all accelerometer‐derived sleep estimates worn on either wrist and PSG were low; however, wide 95% LoA were observed for all sleep estimates, apart from waking time. The automated sleep detection algorithm applied to data from Axivity, GENEActiv and ActiGraph accelerometers, worn on either wrist, provides comparable measures to PSG for SPT‐window and sleep duration, sleep onset and waking time, but a poor measure of wake during the sleep period. [ABSTRACT FROM AUTHOR]

Physical activity has been hypothesized to cause adverse metabolic responses in a minority of participants. We use secondary analysis of a randomized controlled trial to investigate rates of adverse metabolic responses in a population at high risk of type 2 diabetes. METHODS: We investigated data from the PREPARE trial; individuals with impaired glucose tolerance were randomized to the following: control (advice leaflet); intervention 1, a 3-h group-based structured education program aimed at promoting physical activity; or intervention 2, a 3-h structured education program with personalized pedometer use. Intervention 2, but not intervention 1, resulted in increased physical activity at 3, 6, and 12 months. An adverse response was defined as a change of ≥0.8 mmol·L-1 for fasting glucose, ≥1.3 mmol·L-1 for 2-h glucose, ≥0.42 mmol·L-1 for triglycerides, and -0.12 mmol·L-1 or less for HDL-cholesterol. Each group included 29 participants. Data were collected between 2006 and 2008 and analyzed in 2013. RESULTS: In total, 12 (41%) participants in intervention 2 had an adverse response; rates in intervention 1 and the control group were 23 (79%) and 22 (76%), respectively. The odds of an adverse response were reduced in intervention 2 compared with control (OR, 0.22; 95% CI, 0.07-0.69). For the combined cohort, those who had increased physical activity at each time point had reduced odds of an adverse response compared with those who did not (OR, 0.30; 95% CI, 0.10-0.93). CONCLUSION: Although some individuals experienced an adverse metabolic response after a successful physical activity intervention, rates were higher under control conditions. This study does not support the hypothesis that increased physical activity per se increases the risk of an adverse metabolic response. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To describe and evaluate risk assessment tools which detect those with pre-diabetes defined as either impaired glucose tolerance or impaired fasting glucose using an OGTT or as a raised HbA1c. Methods: Tools were identified through a systematic search of PubMed and EMBASE for articles which developed a risk tool to detect those with pre-diabetes. Data were extracted using a standardised data extraction form. Results: Eighteen tools met the inclusion criteria. Eleven tools were derived using logistic regression, six using decision trees and one using support vector machine methodology. Age, body mass index, family history of diabetes and hypertension were the most frequently included variables. The size of the datasets used and the number of events per variable considered were acceptable in all the tools. Missing data were not discussed for 8 (44%) of the tools, 10 (91%) of the logistic tools categorised continuous variables, external validation was carried out for only 7 (39%) of the tools and only 3 tools reported calibration levels. Conclusions: Several risk scores are available to identify those with pre-diabetes. Before these are used in practice, the level of calibration and validity of the tools in the population of interest should be assessed. [Copyright &y& Elsevier]

Introduction Approximately 366 million people worldwide live with diabetes and this figure is expected to rise. Among the correct diagnosis, there will be errors in the diagnosis, classification and coding, resulting in adverse health and financial implications. Aim To determine the prevalence and characteristics of diagnostic errors in people with diabetes managed in primary care settings. Methods We conducted a cross-sectional study in nine general practices in Leicester, UK, from May to August 2011, using a validated electronic toolkit. Searches identified cases with potential errors which were manually checked for accuracy. Results There were 54 088 patients and 2434 (4.5%) diagnosed with diabetes. Out of 316 people identified with potential errors with the toolkit, 180 (57%) had confirmed errors after manually reviewing the records, resulting in an error prevalence of 7.4%. Correctly coded people on registers had significantly greater glycated haemoglobin (HbA1c) reductions. There were no significant differences between patients with and without errors in their HbA1C, body mass index, age and size of practice. There was also no significant association of the errors with pay-for-performance initiatives; however, those patients not on disease register had worse glycaemic control. Conclusions A high prevalence of diabetic diagnostic errors was confirmed using medication, biochemical and demographic data. Larger studies are needed to more accurately assess the scale of this problem. Automation of these processes might be possible, which would allow searches to be even more user friendly. [ABSTRACT FROM AUTHOR]

The article discusses the pandemic has presented unique challenges for people with type 2 diabetes, who comprise a high-risk group for severe COVID-19 infection. Topics include users accessed MyDesmond on computers and smartphones, and the majority found the content sufficiently detailed, providing clear and concise information; and the interactivity incorporated has considered to be engaging by 79% of the respondents.

Introduction: There is recent interest surrounding the use of the triglyceride-to-HDL cholesterol ratio as a surrogate marker of insulin resistance in clinical practice, as it may identify people at high risk of developing diabetes or its complications. However, it has been suggested using this lipid ratio may not be appropriate for measuring insulin resistance in African- Americans, particularly women. We investigated if this inconsistency extended to South Asian women in a UK multi-ethnic cohort of White Europeans and South Asians. Methods: Cross-sectional analysis was done of 729 participants from the ADDITION-Leicester study from 2005 to 2009. The association between tertiles of triglyceride-to-HDL cholesterol ratio to fasting insulin, homeostatic model of assessment for insulin resistance (HOMA1-IR), quantitative insulin sensitivity check index (QUICKI) and glucose: insulin ratio was examined with adjustment for confounding variables. Results: Incremental tertiles of the triglyceride-to-HDL cholesterol ratio demonstrated a significant positive association with levels of fasting insulin, HOMA1-IR, glucose: insulin ratio and a negative association with QUICKI in White European men (n = 255) and women (n = 250) and South Asian men (n = 124) (all p<0.05), but not South Asian women (n = 100). A significant interaction was demonstrated between sex and triglyceride-to-HDL cholesterol ratio tertiles in South Asians only (p<0.05). The area under the receiver operating characteristic curve for triglyceride-to-HDL cholesterol ratio to detect insulin resistance, defined as the cohort HOMA1-IR⩾75th percentile (3.08), was 0.74 (0.67 to 0.81), 0.72 (0.65 to 0.79), 0.75 (0.66 to 0.85) and 0.67 (0.56 to 0.78) in White European men and women, South Asian men and women respectively. The optimal cut-points for detecting insulin resistance were 0.9-1.7 in mmol/l (2.0-3.8 in mg/dl) for the triglyceride-to-HDL ratio. Conclusion: In South Asian women the triglyceride-to-HDL cholesterol ratio was not associated with insulin resistance; therefore there may be limitations in its use as a surrogate marker in this group. [ABSTRACT FROM AUTHOR]

Background: The prevention of type 2 diabetes is a recognised health care priority globally. Within the United Kingdom, there is a lack of research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. This study aims to establish the behavioural and clinical effectiveness of a structured educational programme designed to target perceptions and knowledge of diabetes risk and promote a healthily lifestyle, particularly increased walking activity, in a multi-ethnic population at a high risk of developing type 2 diabetes. Design: Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is change in objectively measured ambulatory activity. Secondary outcomes include progression to type 2 diabetes, biochemical variables (including fasting glucose, 2-h glucose, HbA1c and lipids), anthropometric variables, quality of life and depression. Methods: 10 primary care practices will be recruited to the study (5 intervention, 5 control). Within each practice, individuals at high risk of impaired glucose regulation will be identified using an automated version of the Leicester Risk Assessment tool. Individuals scoring within the 90th percentile in each practice will be invited to take part in the study. Practices will be assigned to either the control group (advice leaflet) or the intervention group, in which participants will be invited to attend a 3 hour structured educational programme designed to promote physical activity and a healthy lifestyle. Participants in the intervention practices will also be invited to attend annual group based maintenance workshops and will receive telephone contact halfway between annual sessions. The study will run from 2010-2014 .Discussion: This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme run within routine primary care in the United Kingdom [ABSTRACT FROM AUTHOR]

The authors reflect on the global efforts to prevent diabetes. They discuss topics on the global prevalence of diabetes mellitus, the strong link between industrialisation, lifestyle and diabetes, and the health and economic burden linked to the disorder. They also stress the importance of targeting population level behaviour and attitudes as part of risk and disease management strategies.

Background: Recent attention has focused on strategies to combat the forecast epidemic of type-2 diabetes (T2DM) and its major vascular sequelae. Metabolic syndrome (MetS) comprises a constellation of factors that increase the risk of cardiovascular disease (CVD) and T2DM. Our study aims to develop a structured self-management education programme for people with MetS, which includes management of cardiovascular and diabetes risk factors, and to determine its impact. This paper describes the rationale and design of the TRIMS study, including intervention development, and presents baseline data.Methods: Subjects recruited from a mixed-ethnic population with MetS were randomised to intervention or control arms. The intervention arm received structured group education based on robust psychological theories and current evidence. The control group received routine care. Follow-up data will be collected at 6 and 12 months. The primary outcome measure will be reversal of metabolic syndrome in the intervention group subjects compared to controls at 12 months follow-up.Results: 82 participants (44% male, 22% South Asian) were recruited between November 2009 and July 2010. Baseline characteristics were similar for both the intervention (n = 42) and control groups (n = 40). Median age was 63 years (IQR 57 - 67), mean waist size 106 cm (SD ± 11), and prescribing of statins and anti-hypertensives was 51% in each case.Conclusion: Results will provide information on changes in diabetes and CVD risk factors and help to inform primary prevention strategies in people with MetS from varied ethnic backgrounds who are at high risk of developing T2DM and CVD. Information gathered in relation to the programme's acceptability and effectiveness in a multi-ethnic population would ensure that our results are widely applicable.Trial Registration: The study is registered at ClinicalTrials.gov, study identifier: NCT01043770. [ABSTRACT FROM AUTHOR]