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Aims This paper aims to investigate whether intraepidermal nerve-fibre density ( IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus. Methods Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (< 3 years) and good glucose control, and in 23 age- and sex-matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy. Results At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/mm). The annual rate of intraepidermal nerve-fibre ( IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean ( se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P < 0.001] and similar to patients without polyneuropathy [12.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control. Conclusions The annual rate of IENF loss in patients with Type 2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Aims To summarize the association between obstructive sleep apnoea and diabetic retinopathy and diabetic maculopathy, and to examine the effects of oxygen desaturation index, mean and minimum oxygen saturation and time spent with < 90% oxygen saturation on diabetic retinopathy and diabetic maculopathy. Methods A systematic search was performed for papers published from inception to January 2014 in MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews using indexed terms and free text. Additional searches were carried out for grey literature. Two authors conducted the study selection and quality assessment. Data extraction was performed by the main author and checked by the other authors. Results One cohort study and 15 cross-sectional studies were included for narrative synthesis and three for meta-analyses. There was no convincing evidence that obstructive sleep apnoea was associated with diabetic retinopathy, although some evidence suggested that obstructive sleep apnoea was associated with greater severity of diabetic retinopathy and advanced diabetic retinopathy in people with Type 2 diabetes. Only six studies examined the impact of obstructive sleep apnoea on diabetic maculopathy and our narrative review suggests there is an association in Type 2 diabetes. Oxygen desaturation index, mean oxygen saturation or time spent with < 90% oxygen saturation were not associated with diabetic retinopathy, and insufficient evidence was available to draw conclusions on their effects on diabetic maculopathy; however, there was evidence from both narrative synthesis and meta-analysis that minimum oxygen saturation had an impact on diabetic retinopathy (pooled odds ratio 0.91, 95% CI 0.87-0.95; I2 = 0%). Conclusions There is a need for large cohort studies with long-term follow-up data to examine the long-term effects of obstructive sleep apnoea and other sleep variables on advanced retinal disease in diabetes. [ABSTRACT FROM AUTHOR]

Aims To investigate the extent of and factors associated with adherence to Type 2 diabetes medication. Methods The CINAHL, Embase, International Pharmaceutical Abstracts, Medline, PubMed and Psych INFO databases were searched for the period January 2004 to July 2013. Papers were included in the present review if they reported the prevalence of adherence (the percentage of the study population that is classified as adherent) to Type 2 diabetes medication and used validated adherence measures with a defined cut-off point to indicate adherence. Reported factors were classified as potential predictors if the studies that examined that particular variable reported consistent findings. Results Of the 27 studies included in the present review, the prevalence of adherence ranged from 38.5 to 93.1%. Only six out of 27 studies (22.2%) reported prevalence of adherence of ≥ 80% among their study population. Depression and medication cost were found to be consistent and potentially modifiable predictors for diabetes medication-taking behaviour. The associations between adherence and other factors were inconsistent among the reviewed studies. Conclusions Adherence to diabetes medication remains an ongoing problem. This review has highlighted the urgent need to develop consensus about what constitutes good adherence in diabetes. Further research is needed to clarify modifiable factors, in addition to depression and medication cost, that influence adherence and may provide a focus for targeted interventions to promote adherence, optimize diabetes control and limit the progression of diabetes. [ABSTRACT FROM AUTHOR]

Aim To test how certain patient factors would influence the decision of Dutch care providers regarding insulin dose adjustments. We hypothesize that some of these decisions would diverge from recent evidence and consensus statements. Methods We developed narrative vignettes describing clinical scenarios of patients receiving basal insulin therapy. For each vignette, the respondents were asked to indicate whether they would advise a change in insulin dose. A total of 520 paper questionnaires were distributed among physicians and nurses in primary and secondary care in the Netherlands. Multivariate linear and logistic regression analyses were performed to identify factors associated with dosing decisions. Results A total of 190 (37%) questionnaires were returned. In cases of a severe rather than mild hypoglycaemic event, care providers were nearly five times more likely to decrease the dose (odds ratio 4.77, 95% CI 1.65-13.75). Care providers were six times more likely to increase the dose when the patient's current dose was low (30 units) rather than high (90 units) (odds ratio 6.38, 95% CI 3.04-13.37). The plasma glucose concentration during a hypoglycaemic event and a known history of cardiovascular disease did not influence the care providers' dosing decisions. Conclusion Evidence regarding the optimum insulin titration is not always translated into clinical practice. When formulating guidelines, misconceptions should be identified and addressed. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 404-409 (2012) Abstract Aims To investigate validity of waist circumference measurements obtained by self-report and self-measurement with non-verbal pictorial instructions among a multi-ethnic population. Methods Five hundred and twenty-six individuals aged 40-75 years (91 South Asian, 430 White European and five other), who attended a screening programme for Type 2 diabetes, estimated their waist circumference and measured their waist with a paper tape measure. Participants were also provided with simple pictorial instructions for measurement of waist circumference in their preferred language and remeasured their waist circumference. We calculated 95% limits of agreement with measures undertaken by a healthcare professional unaware of prior measures. Results Mean age was 56.8 years ( sd 9.0), mean BMI 30.0 kg/m2 ( sd 5.6) and mean waist circumference 98.4 cm ( sd 14.1). Seventy-nine per cent had high waist circumference according to International Diabetes Federation criteria. The mean of participants' self-reported value was 6.8 cm lower than the healthcare professional measure ( sd 8.8; 95% limits of agreement −10.4 to 24.0 cm), with significant differences by sex and ethnicity (South Asian men 7.5 cm, South Asian women 0.1 cm, White European men 7.8 cm, White European women 7.0 cm, P < 0.001). Compared with healthcare professional measures, mean self-measured waist circumference was very similar, both with instructions (0.4 cm higher; sd 5.5 cm; −11.1 to 10.4 cm) and without instructions (0.5 cm lower; sd 5.6; −10.4 to 11.4 cm), but with significant differences by sex and ethnicity ( P < 0.001). Conclusions There was systematic underestimation of self-reported waist circumference in this multi-ethnic UK population. The magnitude of underestimation might reduce the performance of risk scores; however, this can be corrected through self-measurement with pictorial instructions. [ABSTRACT FROM AUTHOR]

Aims The burden of diabetes is considerable for racial and ethnic minority populations in many places in the USA and worldwide, often disproportionately affecting immigrant communities. This paper reports findings from a community-based participatory research study that described diabetes risk and awareness, assessed the association between perceived and actual risk (high, two or more diabetes risk factors; low, fewer than two risk factors) and identified factors associated with disease risk among Chinese and Hispanic / Latino immigrant populations in Portland, OR, USA. Methods Cross-sectional, self-reported data were collected from a purposive sample of 324 Chinese (n = 159) and Hispanic / Latino (n = 165) adults, aged 18-86 years [mean (SD) age, 45.2(17.9) years; 50.7% women). Analyses described differences in variable distributions. Logistic regression estimated odds ratios and 95%confidence intervals in pooled and ethnic group-specific samples. Results Approximately 43% of participants were at high risk for diabetes, regardless of ethnicity or age. Of those unaware of their risk, or who perceived themselves not to be at risk, 25-53%had two or more risk factors (high risk); these patterns varied by ethnicity. The proportion of participants who reported two or more risk factors and were unaware of their risk status (31.8% Hispanic / Latino; 17% Chinese) or self-identified as not at risk (12.5% Hispanic / Latino; 13.0% Chinese) was substantial. Factors associated with diabetes risk also varied by ethnicity. Conclusions This study assessed the degree and determinants of diabetes risk and awareness among local Hispanic / Latino and Chinese communities and identified significant variation between groups. The results are important because they highlight substantial diabetes risk among persons who misestimate or are unaware of their risk status, regardless of ethnicity, and, in the USA, the Chinese immigrant population commonly is not considered a high-risk group for Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims To assess the effect of mobile phone intervention on glycaemic control in diabetes self-management. Methods We searched three electronic databases (PubMed, EMBASE and Cochrane Library) using the following terms: diabetes or diabetes mellitus and mobile phone or cellular phone, or text message.We also manually searched reference lists of relevant papers to identify additional studies. Clinical studies that used mobile phone intervention and reported changes in glycosylated haemoglobin (HbA1c) values in patients with diabetes were reviewed. The study design, intervention methods, sample size and clinical outcomes were extracted from each trial. The results of the HbA1c change in the trials were pooled using meta-analysis methods. Results A total of 22 trials were selected for the review. Meta-analysis among 1657 participants showed that mobile phone interventions for diabetes self-management reduced HbA1c values by amean of 0.5% [6 mmol / mol; 95% confidence interval, 0.3-0.7% (4-8 mmol/ mol)] over a median of 6 months follow-up duration. In subgroup analysis, 11 studies among Type 2 diabetes patients reported significantly greater reduction in HbA1c than studies among Type 1 diabetes patients [0.8 (9 mmol/ mol) vs. 0.3% (3 mmol / mol); P = 0.02]. The effect of mobile phone intervention did not significantly differ by other participant characteristics or intervention strategies. Conclusions Results pooled from the included trials provided strong evidence that mobile phone intervention led to statistically significant improvement in glycaemic control and self-management in diabetes care, especially for Type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to assess the clinical performance and user acceptance of capillary blood samples prepared remotely using the MiniCollect® capillary blood collection device as an alternative to blood collection by venepuncture for glycated haemoglobin (HbA1c) analysis. Methods: Following written informed consent, a cross‐sectional study was conducted in individuals aged ≥18 years with any type of diabetes who routinely self‐monitor their blood glucose. Eligible participants recruited whilst attending their routine clinical appointments were required to provide a venous blood sample, prepare a capillary blood sample at home (remotely) and complete a bespoke questionnaire. HbA1c in whole blood collected in ethylenediaminetetraacetic acid was determined by capillary electrophoresis on the Sebia Capillary's 3 Tera analyser following standard operating procedure. Results: HbA1c results from both venous and capillary collection demonstrated good agreement. Passing‐Bablok regression: y = 0 + 1x (p = 0.18), Spearman correlation r = 0.986, p < 0.0001. The Bland–Altman difference plot provided a mean difference of 0.3 mmol/mol (2.2%). Over half of the participants found the MiniCollect device easy to use. The majority of participants were in favour of the remote capillary blood collection service and would use it if routinely available. Conclusion: The home collection of capillary blood for HbA1c determination is a valuable and convenient alternative to standard venous blood collection as it provides an opportunity to support routine HbA1c monitoring, whilst mitigating the transmission of SARS‐CoV‐2. This service would additionally allow individuals to attend clinic visits with a HbA1c value, ensuring optimal continuance of patient care for individuals with diabetes. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 1289-1294 (2010) Aims At any given time, people with diabetes occupy approximately 10-20% of acute hospital beds. In addition, diabetes is associated with a greater length of stay. Patients undergoing elective procedures occupy approximately 50% of hospital beds. The aim of this 12-month project was to improve the quality of diabetes care for elective inpatients. The primary outcome measure was length of stay. Methods A team was established to improve the quality of care and reduce the length of stay of all patients admitted electively with diabetes. Specific areas of focus were surgical pre-assessment, planning the admission, post-operative care and planning a safe discharge. A retrospective audit of all elective patients with a coded diagnosis of diabetes admitted between June 2008 and June 2009 was performed. Results Comparing the year of the project with the preceding year day-case rates for patients with diabetes increased by 34.8% for diabetes vs. 13.7% for the total hospital population ( P for difference = 0.048). There was a significant fall in diabetes length of stay of 0.34 days comparing 2008 and 2009 ( P = 0.040). Over the same period, we have shown a smaller reduction in length of stay for all other admissions of 0.08 days ( p = 0.039). Conclusion A team specifically employed to focus on elective inpatient diabetes care have a significant impact on length of stay of this patient group with potential cost savings. [ABSTRACT FROM AUTHOR]

Background: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively. Methods: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT‐Protect 1 and 2, respectively. End points were two‐step (RET2) and three‐step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT‐Protect 1. The identified peptides were then validated cross‐sectionally in the remaining 1/3 from DIRECT‐Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT‐Protect 1 and 2 cohorts and significant peptides were tested longitudinally. Results: Follow‐up ranged 4.0–4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: −.223, p < 0.001 and Rho: −.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types. Conclusions: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR. [ABSTRACT FROM AUTHOR]

Aims: To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes). Methods: We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta‐analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily. Results: The absolute changes in HbA1c were similar to those reported in the NG17. However, all 95% credible intervals for change in HbA1c point estimates crossed the line of null effect, except for detemir twice daily (in the NICE and extended 2017 NMAs) and NPH four times daily. In the detemir twice‐daily centred post hoc analysis, the 95% credible intervals for change in HbA1c crossed the line of null effect for all basal therapies, except NPH. Conclusions: In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat‐to‐target, which minimize differences in HbA1c. In the NMAs, statistical significance was severely undermined by the wide credible intervals. Despite these limitations, point estimates of HbA1c were used to rank the insulins and formed the basis of NG17 guidance. This study queries whether such analyses should be used to make specific clinical recommendations. What's new?: This study found no significant differences in HbA1c reduction between twice‐daily detemir and modern basal insulin comparators in efficacy trials; the apparent wide variation in HbA1c undermines the statistical robustness and the clinical relevance of the recommendation in the current National Institute of Health and Care Excellence (NICE) guidelines for type 1 diabetes in adults (NG17).The analyses highlight the importance of the quantity and quality of data used in network meta‐analyses to allow clinically meaningful recommendations.With the lack of differentiating evidence to support twice‐daily detemir as the basal insulin of choice for type 1 diabetes, selection of basal insulin should be personalized to individual needs. [ABSTRACT FROM AUTHOR]

Aim: To study cell‐mediated immunity in the feet of people with type 2 diabetes with polyneuropathy. Methods: In a cohort comprising people with type 2 diabetes with polyneuropathy (n = 17) and without polyneuropathy (n = 12) and a healthy control group (n = 12) indurations due to delayed‐type hypersensitivity responses to intracutaneous Candida albicans antigen were determined in the foot and compared with those in the arm (an area relatively spared in diabetic polyneuropathy). The sizes of indurations on the foot were correlated with electromyographic measurements in the participants with diabetes. Results: No differences were observed in the median size of indurations between the foot and arm in healthy controls and participants without polyneuropathy; in participants with polyneuropathy, induration sizes on the foot were smaller than on the arm: 0 (95% CI 0 to 1) vs 5 (95% CI 2 to 6) mm (P < 0.01). In participants with diabetes, larger indurations correlated with better nerve function (Spearman's rho 0.35 to 0.39). Conclusion: Our findings suggest that diabetic peripheral polyneuropathy negatively affects cell‐mediated immunity in the foot. (Clinical Trials registry no.: NCT01370837) What's new?: Local immune responses can be impaired as a result of neurological deficits.Diabetic peripheral neuropathy could negatively affect cell‐mediated immunity selectively in the foot, the site most frequently and severely affected by peripheral neuropathy.More severe impairment of cell‐mediated immunity correlates with worse peripheral nerve function as measured by electromyography.Our study is the first to suggest the presence of locally diminished cell‐mediated immunity in the foot in people with diabetic peripheral neuropathy.Impaired cellular immunity in the foot may explain the paucity of signs of inflammation in diabetic foot infections. [ABSTRACT FROM AUTHOR]

Aims To develop and validate a self-report measure designed to assess perceived and experienced stigma for adults with Type 1 diabetes: the Type 1 Diabetes Stigma Assessment Scale (DSAS-1). Methods A large item-pool (64 items) was drafted based on qualitative data from interviews with 27 adults with Type 1 diabetes. Eleven adults with Type 1 diabetes completed the draft questionnaire (responding to items using a five-point Likert scale), and participated in cognitive debriefing interviews. Based on their feedback, the item-pool was reduced and refined. Adults with Type 1 diabetes ( N=898) completed an online survey including the draft stigma questionnaire (41 items) and other validated measures. Psychometric validation included principal components analysis and confirmatory factor analysis (split samples), internal consistency reliability assessment and Spearman's rho correlations. Results Scale reduction techniques resulted in 19 items ( α=0.93). An unforced three-factor solution suggested three subscales: Treated Differently (six items, α=0.89); Blame and Judgement (six items, α=0.88); and Identity Concerns (seven items, α=0.89). This was corroborated with a confirmatory factor analysis, which demonstrated reasonable model fit with the three factors; less so for a single-factor model. Satisfactory concurrent, convergent and discriminant validity were demonstrated. Conclusions The 19-item DSAS-1 is a valid and reliable measure of the perceptions and experiences of Type 1 diabetes stigma. This novel, relatively brief measure has satisfactory psychometric properties. The DSAS-1 is now available for investigations into the nature and magnitude of the relationships between diabetes stigma and diabetes self-care behaviours and outcomes. [ABSTRACT FROM AUTHOR]

Aim The role of metformin in lactic acidosis is regularly questioned. Arguments against a causal role for metformin in lactic acidosis occurrence are the lack of correlation between plasma metformin and lactate levels, as well as between metformin plasma levels and mortality. We aim to analyse these correlations in a large series of lactic acidosis cases recorded in the French nationwide pharmacovigilance database. Methods All cases of lactic acidosis spontaneously reported between 1985 and October 2013 associated with metformin exposure were extracted from the pharmacovigilance database. We assessed the statistical correlations between prescribed daily doses of metformin, plasma concentrations of metformin and lactate, pH and plasma creatinine, as well as the relationship between mortality and these variables. Results Seven hundred and twenty-seven cases of lactic acidosis were reported during the period. Metformin plasma concentration was documented for 260 patients, lactate plasma concentration for 556 patients, pH for 502 patients, creatinine for 397 patients and the vital outcome for 713 patients. Metformin plasma concentration, lactate concentration, pH and plasma creatinine were all correlated ( P < 0.001). There were significant differences between surviving and deceased patients in terms of metformin plasma levels (25.2 vs. 37.4 mg/l, P = 0.002) and lactate concentrations (10.8 vs. 16.3 mmol/l, P < 0.001). Thirty per cent of patients died when metformin concentration was > 5 mg/l compared with 11% for patients with concentration < 5 mg/l ( P = 0.003). Conclusions Our data suggest that metformin accumulation contributes to the pathogenesis and prognosis of lactic acidosis. [ABSTRACT FROM AUTHOR]

Aim To determine what proportion of women with gestational diabetes underestimate their diabetes risk and identify factors associated with low diabetes risk perception. Methods Participants included pregnant adult women with gestational diabetes between 2009 and 2012 across seven diabetes clinics in Ontario, Canada. Data were collected through chart review and a survey that included a diabetes risk perception question. Results Of the 614 of 902 women (68% response rate) with gestational diabetes, 89% correctly responded that gestational diabetes increases the risk for developing diabetes. However, 47.1% of women perceived themselves to be at low risk for developing diabetes within 10 years. On multivariable analysis, BMI < 25 kg/m2, absent previous gestational diabetes history, absent diabetes family history and absent insulin use were appropriately associated with low diabetes risk perception. However, compared with Caucasian ethnicity, high-risk ethnicity (Aboriginal, Latin American, West Indian, South Asian, Middle Eastern, Filipino, Black, Pacific Islander) [odds ratio ( OR) 2.07; 95% CI 1.30-3.31] and East and South East Asian ethnicity ( OR 2.01; 1.10-3.67) were associated with low diabetes risk perception. After further adjustment for immigration, only high-risk ethnicity remained a predictor of low diabetes risk perception ( OR 1.86; 1.09-3.19), whereas East and South East Asian ethnicity did not ( OR 1.67; 0.86-3.22). Conclusions Although the majority of women recognized gestational diabetes as a risk factor for diabetes, almost half underestimated their personal high diabetes risk despite prenatal care. Furthermore, women from high-risk ethnic groups were more likely to underestimate their risk, even after adjusting for immigration. Interventions tailored to these groups are necessary to enhance perceived diabetes risk. [ABSTRACT FROM AUTHOR]

Aims To assess serum oestrogen levels and oestrogenic activity in adolescents with Type 1 diabetes compared with a healthy control group. Methods We conducted a cross-sectional study that evaluated adolescents with Type 1 diabetes ( n = 38) and healthy adolescents (control group; n = 32). Serum oestrogens, urinary oestrogen metabolites and serum oestrogenic activity were assessed. Oestrogenic activity was evaluated in an in vitro cell proliferation assay using a modified E-screen assay with MCF-7/ BUS cells. Results Adolescents with Type 1 diabetes had lower oestrogenic activity levels in both phases of the menstrual cycle compared with the control group (follicular phase: 76 vs 94%; luteal phase: 97 vs 131%; P < 0.01), even after adjusting for BMI, oestradiol and oestrone levels. Postmenarcheal adolescents with Type 1 diabetes had lower oestradiol levels compared with control subjects in the follicular phase (63.3 pmol/l vs 89.4 pmol/l; P < 0.01) and higher oestrone levels compared with controls in the luteal phase (196 vs 151.9 pmol/l; P < 0.05). Conclusions Adolescents with Type 1 diabetes had lower levels of serum oestrogenic activity, and these were lower than expected based on their serum oestradiol levels. We postulate that changes in the serum milieu of oestrogens in patients with Type 1 diabetes may explain their decreased oestrogenic activity and may play a role in their adverse metabolic profile. [ABSTRACT FROM AUTHOR]

Aim The study tested the hypothesis that doctors using an insulin information checklist during simulated insulin initiation would impart more information regarding insulin use. Methods A total of 128 simulations were conducted. Doctors ( n = 64) were recruited from practitioners recently completing internship ( n = 19) and those established in primary care ( n = 45). Both groups of doctors were strata randomized to control ( n = 32) and intervention groups ( n = 32), so that each group contained equal numbers. Doctors in each group experienced two identical simulations of insulin initiation with an intervening period of 10 min. Doctors in the intervention arm were introduced to an insulin initiation checklist, which they reviewed independently and utilized in the second simulation. Trained assessors captured the provision of education in 21 predefined educational areas. Differences in the change of the total education provided between the first and second simulations were assessed using linear regression. Results The difference in the mean change of education provided between the first and second simulations within the 21 educational areas for the control and treatment groups was 9.7 [95% confidence interval ( CI): 8.8-11.1, P < 0.001] - an increase of 46.2%. The difference for the 15 areas relevant to pen use was 7.3 (95% CI: 6.2-8.4, P < 0.001) - an increase of 51.6%. Conclusions The checklist resulted in doctors providing significantly more education applicable to syringe and insulin pen routes of insulin administration during simulations. Further research is needed on the checklist's impact on healthcare professionals and patient outcomes in the clinical context. (Clinical Trials Registry No: NCT02266303) [ABSTRACT FROM AUTHOR]

Aims To assess the ways in which healthcare professionals address psychological problems of adults with diabetes in the second Diabetes Attitudes, Wishes and Needs ( DAWN2™) study. Methods Approximately 120 primary care physicians, 80 diabetes specialists and 80 nurses and dietitians providing diabetes care participated in each of 17 countries ( N=4785). Multiple regression analyses were used to evaluate independent statistically significant associations of respondent attributes concerning psychological care strategies, including assessment of diabetes impact on the patient's life, assessment of depression, provision of psychological assessment and support, and coordination with mental health professionals. Results Psychological care strategies were positively associated with each other but differed by healthcare practice site and discipline; nurses and dietitians were less likely to assess depression than other healthcare professionals, while primary care physicians were less likely to coordinate with mental health specialists or ask patients how diabetes affects their lives. Psychological care was positively associated with healthcare professionals' beliefs that patients need help dealing with emotional issues and that clinical success depends on doing so, and also with level of psychological care training, multidisciplinary team membership and availability of resources for psychological care. There were significant between-country variations in psychological care strategies, before and after adjustment for individual-level factors, and significant country-by-covariate interactions for almost all individual-level factors investigated. Conclusions Improvements in training and resources, recognition and assessment of psychological problems, and increased belief in the efficacy of psychological support may enhance healthcare professionals' efforts to address psychological problems in adults with diabetes. [ABSTRACT FROM AUTHOR]

Aims To assess country- and individual-level correlates of psychological outcomes, and differences among countries in the associations of individual characteristics with psychological outcomes among adults with diabetes. Methods The second Diabetes Attitudes, Wishes and Needs ( DAWN2™) study assessed self-reported characteristics of people with diabetes in 17 countries, including 1368 adults with Type 1 diabetes and 7228 with Type 2 diabetes. In each country, a sample of 500 adults, stratified by diabetes type and treatment, completed a questionnaire incorporating the validated WHO-5 wellbeing index, the WHOQOL- BREF, and the five-item Problem Areas in Diabetes Scale, as well as the newly developed Diabetes Impact on Life Dimensions that assessed impact ranging from very positive to very negative, with no impact as the midpoint. Multilevel regression analyses identified significant ( P < 0.05) independent correlates of psychological outcomes. Results There were significant variations in all outcomes across countries before adjustment for individual-level factors; adjustment reduced between-country disparities. Worse psychological outcomes were associated with more complications, incidence of hypoglycaemia, hypoglycaemic medication, perceived burden of diabetes, family conflict and experience of discrimination. Better psychological outcomes were associated with higher self-rated health, greater access to diabetes education and healthcare, and more psychosocial support from others. The associations of many factors with the outcomes were mediated by modifiable factors. The association of all factors with the outcomes varied across (interacted with) countries, highlighting the need for country-specific analyses. Conclusions Improvements in modifiable risk factors (reductions in burden and increases in support) may lead to better psychological outcomes in adults with diabetes. [ABSTRACT FROM AUTHOR]

Aim Although pedometer intervention is effective in increasing physical activity among adults with Type 2 diabetes, its impact on weight loss remains unclear. This meta-analysis was aimed to assess whether pedometer intervention promotes weight loss. Methods Three different databases were searched for randomized controlled trials (RCTs) published in English up to April 2015. Studies were included if they investigated the effects of pedometer intervention on weight loss, as measured by BMI or weight. Effect sizes were aggregated using a random-effects model. Subgroup and meta-regression analyses were used to identify potential moderators. Eleven RCTs with 1258 participants were included. All enrolled participants were overweight or obese. Results Pedometer intervention led to significantly decreased BMI [weighted mean difference (WMD) −0.15 kg/m2, 95% confidence interval (CI) −0.29 to −0.02 kg/m2] and reduced weight (WMD −0.65 kg, 95% CI −1.12 to −0.17 kg). Dietary counselling seemed to be a key predictor of the observed changes. However, none of the following variables had a significant influence: step goal setting, baseline age, BMI, weight, sex distribution, disease duration, intervention duration, and baseline values or change scores for total or moderate-to-vigorous physical activity. After completion of the pedometer intervention, non-significant declines in BMI and weight were observed during the follow-up periods. Conclusions Pedometer intervention promotes modest weight loss, but its association with physical activity requires further clarification. Future studies are also required to document dietary and sedentary behaviour changes to facilitate the use of pedometers for weight loss in overweight and obese adults with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims Increased plasma uric acid ( PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. Methods PUA, GFR (inulin) and effective renal plasma flow ( ERPF; para-aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent ( RA) and efferent ( RE) arteriolar resistances, glomerular hydrostatic pressure ( PGLO) and filtration pressure (Δ PF). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. Results In patients with Type 1 diabetes, higher PUA correlated with lower PGLO ( P = 0.002) and Δ PF ( P = 0.0007), with higher RA ( P = 0.001), but not with RE ( P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR ( P = 0.0007), ERPF ( P = 0.008), RBF ( P = 0.047) and higher RVR ( P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. Conclusions The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated RA. PUA-mediated RA may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation. [ABSTRACT FROM AUTHOR]

Aims To assess the cost-effectiveness of adopting risk-stratified approaches to extended screening intervals in the national diabetic retinopathy screening programme in Scotland. Methods A continuous-time hidden Markov model was fitted to national longitudinal screening data to derive transition probabilities between observed non-referable and referable retinopathy states. These were incorporated in a decision model simulating progression, costs and visual acuity outcomes for a synthetic cohort with a covariate distribution matching that of the Scottish diabetic screening population. The cost-effectiveness of adopting extended (2-year) screening for groups with no observed retinopathy was then assessed over a 30-year time horizon. Results Individuals with a current grade of no retinopathy on two consecutive screening episodes face the lowest risk of progressing to referable disease. For the cohort as a whole, the incremental cost per quality-adjusted life year gained for annual vs. biennial screening ranged from approximately £74 000 (for those with no retinopathy and a prior observed grade of mild or observable background retinopathy) to approximately £232 000 per quality-adjusted life year gained (for those with no retinopathy on two consecutive screening episodes). The corresponding incremental cost-effectiveness ratios in the subgroup with Type 1 diabetes were substantially lower; approximately £22 000 to £85 000 per quality-adjusted life year gained, respectively. Conclusions Biennial screening for individuals with diabetes who have no retinopathy is likely to deliver significant savings for a very small increase in the risk of adverse visual acuity and quality of life outcomes. There is greater uncertainty regarding the long-term cost-effectiveness of adopting biennial screening in younger people with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C-peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non-response to glucagon-like peptide-1 receptor agonists, and thiazolidinediones are more effective in insulin-resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity-onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 ( OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome-wide approaches and the potential of other 'omics', including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments. [ABSTRACT FROM AUTHOR]

Aims To investigate the effectiveness of a diabetes virtual clinic to enhance diabetes in primary care by developing clinical management plans for patients with suboptimal metabolic control and/or case complexity. Methods A prospective study with randomized allocation to virtual clinic or usual care. Patients with Type 2 diabetes ( n = 208) were recruited from six general practices in South London. The primary outcome for the study was glycaemic control, secondary outcomes included: lipids, blood pressure, weight (kg and BMI) and renal function ( eGFR). Data were collected from participants' records at baseline and 12 months. We also considered process measures including therapy optimization. Results The 12-month data show equivalence between the virtual clinic and control groups for glycaemic control with both achieving clinically significant reductions in HbA1c of 8 mmol/mol (0.6 ± 1.7%) and 10 mmol/mol (0.8 ± 1.9%), respectively ( P = 0.4). The virtual clinic group showed superiority over the intervention group for blood pressure control with a mean reduction in systolic blood pressure of 6 ± 16 mmHg compared with an increased of 2 ± 18 mmHg in the control group ( P = 0.008). There were no significant differences between the groups in terms of cholesterol, weight and renal function. Process measures showed an increased level of therapy adjustment in the virtual clinic group. Conclusion The virtual clinic model explored in this study showed a clinically important improvement in glycaemic control. Although this improvement was not superior to that observed in the control participants, this might be attributable to the systemic impact of the virtual clinic on the practice as a whole. [ABSTRACT FROM AUTHOR]

Diabetes disproportionately affects disadvantaged populations. Eighty percent of deaths directly caused by diabetes occurred in low- and middle-income countries. In high-income countries, there are marked disparities in diabetes control among racial/ethnic minorities and those with low socio-economic status. Innovative, effective and cost-effective strategies are needed to improve diabetes outcomes in these populations. Technological advances, peer educators and community health workers have expanded methodologies to reach, educate and monitor individuals with diabetes. In the present manuscript we review the outcomes of these strategies, and describe the barriers to and facilitators of these approaches for improving diabetes outcomes. [ABSTRACT FROM AUTHOR]

Aim To use continuous glucose monitoring to examine the effects of insulin initiation with glargine, with or without glulisine, on glycaemic variability and glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral hypoglycaemic agents in primary healthcare. Methods We conducted a post hoc analysis of continuous glucose monitoring data from 89 participants at baseline and at 24 weeks after insulin commencement. Indicators of glycaemic variability (standard deviation, J-index and mean amplitude of glycaemic excursion) and glycaemia (HbA1c, mean glucose, area under the glucose-time curve) were assessed. Multi-level regression analysis was used to identify the predictors of change. Results Complete glycaemic variability data were available for 78 participants. Of these participants, 41% were women, their mean ( sd) age was 59.2 (10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5, 13.3) years and the median (interquartile range) baseline HbA1c was 82.5 (71.6, 96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with standard deviation ( r = −0.30) and mean amplitude of glycaemic excursion ( r = −0.26), but not with J-index; HbA1c correlated with J-index ( r = 0.61) but not with mean amplitude of glycaemic excursion and standard deviation. After insulin initiation the mean ( sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6) mmol/l; P < 0.001], as did the median (interquartile range) J-index [from 66.9 (47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l; P < 0.001]. Baseline HbA1c correlated with a greater J-index reduction ( r = −0.45; P < 0.001). The mean amplitude of glycaemic excursion and standard deviation values were unchanged. The baseline temporal profile, showing elevated postprandial morning glucose levels, was unchanged after insulin initiation, despite an overall reduction in glycaemia. Conclusion Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic agents. The most significant postprandial excursions were seen in the morning, which identifies prebreakfast as the most effective target for short-acting insulin therapy. [ABSTRACT FROM AUTHOR]

Aim To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. Methods Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous investigation at a memory clinic; and inability to write or read. Patients first filled out two self-administered cognitive tests (Test Your Memory and Self-Administered Gerocognitive Examination). Secondly, a general practitioner, blinded to Test Your Memory and Self-Administered Gerocognitive Examination scores, performed a structured evaluation using the Mini-Mental State Examination. Subsequently, patients suspected of cognitive impairment (on either the cognitive tests or general practitioner evaluation) and a random sample of 30% of patients not suspected of cognitive impairment were evaluated at a memory clinic. Diagnostic accuracy and area under the curve were determined for the Test Your Memory, Self-Administered Gerocognitive Examination and general practitioner evaluation compared with a memory clinic evaluation to detect cognitive impairment (mild cognitive impairment or dementia). Results A total of 44 participants were diagnosed with cognitive impairment. The Test Your Memory and Self-Administered Gerocognitive Examination questionnaires had negative predictive values of 81 and 85%, respectively. Positive predictive values were 39 and 40%, respectively. The general practitioner evaluation had a negative predictive value of 83% and positive predictive value of 64%. The area under the curve was ~0.70 for all tests. Conclusions Both the tests evaluated in the present study can easily be used in case-finding strategies for cognitive impairment in patients with Type 2 diabetes in primary care. The Self-Administered Gerocognitive Examination had the best diagnostic accuracy and therefore we would have a slight preference for this test. Applying the Self-Administered Gerocognitive Examination would considerably reduce the number of patients in whom the general practitioner needs to evaluate cognitive functioning to tailor diabetes treatment. [ABSTRACT FROM AUTHOR]

Aims To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed. Methods Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores. Results In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28). Conclusions In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure. [ABSTRACT FROM AUTHOR]

Aim To perform a detailed analysis of patients with recurrent diabetic ketoacidosis admissions in order to establish risk factors for readmission. Methods The medical records of all adults and young people (> 15 years) with Type 1 diabetes admitted to Auckland City Hospital over a 15-year period from 1997 to 2011 with a primary diagnosis of ketoacidosis were analysed. Patients readmitted with ketoacidosis within 5 years of their index admission were identified and compared with patients without ketoacidosis readmission who were matched for age, gender, ethnicity and duration of diabetes. Results A total of 268 patients accounted for a total of 412 admissions. In all, 58 patients had more than one admission for diabetic ketoacidosis during this period. Of these, 40 patients readmitted with diabetic ketoacidosis were compared with matched control subjects ( n = 40) who had only one admission for diabetic ketoacidosis. The mean ± sd age of the cohort was 31 ± 12 years. The readmission group had more severe diabetic ketoacidosis and poorer glycaemic control. Alcohol abuse was commonly noted in both groups, with insulin dose omission being the main contributor to the development of ketoacidosis. Both groups had high rates of clinic non-attendance. There were no other differences noted between the groups. Conclusion When patients with recurrent diabetic ketoacidosis were matched for age, duration of diabetes, gender and ethnicity with patients who had only one admission for diabetic ketoacidosis, few differences were noted. This makes designing intervention strategies to reduce readmission with diabetic ketoacidosis difficult. [ABSTRACT FROM AUTHOR]

Aims To investigate whether serum complement C3 is related to the prevalence and incidence of prediabetes in an adult population. Methods A cross-sectional ( n = 10 206) and prospective cohort study ( n = 3333), with a mean (range; 95% CI) follow-up of 2.63 (1-6; 2.58-2.68) years, was conducted in people recruited from the Health Management Centre of Tianjin Medical University General Hospital in Tianjin, China. Measurement of serum C3 concentration, blood fasting glucose, oral glucose tolerance, HbA1c and other potential confounding factors was performed at baseline and each year during the follow-up. Prediabetes was defined according to the criteria of the American Diabetes Association. Adjusted logistic and Cox proportional hazards regression models were used to assess the relationships between C3 quintiles and prediabetes. Results The prevalence and incidence of prediabetes were 38.5% and 119 per 1000 person-years, respectively. In cross-sectional analysis, after adjustment for potential confounders, the odds ratios of prediabetes for increasing quintiles of C3 were 1.00 (reference), 1.32 (95% CI 1.14-1.53), 1.37 (95% CI 1.18-1.59), 1.75 (95% CI 1.51-2.03), 2.25 (95% CI 1.93-2.62; P for trend < 0.0001). In the cohort analysis, the multiple-adjusted hazard ratio of prediabetes in the highest quintile of baseline C3 was 1.43 (95% CI 1.15, 1.78; P for trend < 0.001), when compared with the lowest quintile. Conclusions These findings indicate that elevated serum C3 levels are significantly related to an increased risk of developing prediabetes in an adult population, suggesting that C3 can be used as a biomarker in high-risk individuals to improve primary prevention of prediabetes and diabetes. [ABSTRACT FROM AUTHOR]

Aims To investigate the incidence of all-cause mortality, composite mortality and morbidity in people with Type 1 diabetes formerly randomized in the Stockholm Diabetes Intervention Study. Methods A total of 102 people with Type 1 diabetes were randomized in the period 1982-1984 to intensified conventional treatment or standard treatment with insulin for a mean of 7.5 years. We prospectively re-evaluated this cohort for the period until 2011 with regard to all-cause mortality and composite mortality, which consisted of myocardial infarction, stroke and end-stage renal disease as primary endpoints. Secondary endpoints were first-time hospitalization for myocardial infarction and stroke or end-stage renal disease. Data on HbA1c levels (mean of 22 values/person) were retrospectively collected between 1996 and 2011. Results During the median follow-up of 28 years, 22 people died: seven in the intensified conventional insulin group compared with 15 in the standard treatment group ( P = 0.30). With regard to composite mortality, six people in the intensified conventional insulin group died compared with 11 in the standard treatment group ( P = 0.56). For the secondary endpoints, 11 people in the intensified conventional insulin group developed myocardial infarction or stroke compared with 17 in the standard treatment group ( P = 0.72), and one person in the intensified conventional insulin compared with seven people in the standard treatment group developed end-stage renal disease ( P = 0.09). Mean HbA1c levels did not differ between groups during the follow-up years. Conclusions All-cause mortality, cardiovascular morbidity and progression to end-stage renal disease did not differ in people with Type 1 diabetes earlier randomized to intensified insulin treatment. [ABSTRACT FROM AUTHOR]

Aims To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. Results Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively ( P = 0.001). No relationship was found for gamma-glutamyltransferase. Conclusions The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health. [ABSTRACT FROM AUTHOR]

Aim To assess the effect of a 5-day structured education course (Kids in Control of Food; KICk- OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes. Methods This was a cluster-randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk- OFF courses, whereas control centres delivered usual care. Participants were 11-16 years of age and had Type 1 diabetes for at least one year. The KICk- OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self-efficacy. Results Three hundred and ninety-six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75-81) vs. 76 mmol/mol (74-79) [9.3% (9-9.6%) vs. 9.1% (8.9-9.4%); 24 months: 77 mmol/mol (74-79) vs. 78 mmol/mol (75-81) (9.2% (8.9-9.4%) vs. 9.3% (9-9.6%)], adjusted mean difference, -2.0 mmol/mol (6.5-2.5) [2.3% (-2.7% to 2.4%)], P = 0.38. Conclusions Attending a KICk- OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c, was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268) [ABSTRACT FROM AUTHOR]

Aims To examine whether early endocrinologist care reduces the risk of cardiovascular complications among newly diagnosed patients with diabetes of differing complexity. Methods We conducted a population-based propensity score-matched cohort study using provincial health data from Ontario, Canada. Adults (≥ 30 years) diagnosed with diabetes between 1 April 1998 and 31 March 2006 who received endocrinologist care in the first year of diagnosis were matched to a comparison group receiving primary care alone (N = 79 020) based on propensity scores and medical complexity (assigned using information on chronic conditions). Individuals were followed for 3- and 5-year outcomes, including non-fatal acute myocardial infarction or coronary heart disease death (primary endpoint), major cardiovascular events (acute myocardial infarction, stroke) or all-cause death, amputation and end-stage renal disease. Results Among medically complex patients, early endocrinologist care was associated with a lower 3-year incidence of the primary endpoint (hazard ratio 0.89, 95% CI 0.78-1.01) and major cardiovascular events or all-cause death (hazard ratio 0.91, 95% CI 0.85-0.97). These effects persisted after accounting for a higher incidence of end-stage renal disease on follow-up and were greatest in those with ≥ 3 visits to an endocrinologist (primary endpoint: hazard ratio 0.69, 95% CI 0.56-0.86 and 0.61, 95% CI 0.45-0.82, for unadjusted and end-stage renal disease adjusted analyses, respectively). In contrast, no benefit was observed in the non-medically complex subgroup. Overall effects were similar at 5 years. Conclusions Early endocrinologist care is associated with a lower incidence of cardiovascular events and death among newly diagnosed patients with diabetes who have comorbid medical conditions. [ABSTRACT FROM AUTHOR]

Aims To investigate the long-term efficacy and safety of empagliflozin as add-on to metformin in people with Type 2 diabetes. Methods Of 637 participants treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks, 463 (72.7%) were treated in a double-blind extension trial for ≥ 52 weeks. Prespecified exploratory endpoints included changes from baseline in HbA1c, weight and blood pressure at week 76. Results Compared with placebo, adjusted mean changes from baseline in HbA1c (overall baseline mean ± sd 63 ± 9 mmol/mol [7.9 ± 0.9%]) were â'7 mmol/mol [(â'0.6%) 95% CI â'8, â'5 mmol/mol (â'0.8, â'0.5%); P < 0.001] and â'8 mmol/mol [(â'0.7%) 95% CI â'10, â'6 mmol/mol (â'0.9, â'0.6%); P < 0.001], for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight were â'1.9 kg (95% CI â'2.5, â'1.3; P < 0.001) and â'2.2 kg (95% CI â'2.8, â'1.6; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to sustained reductions in systolic blood pressure vs. placebo. Adverse events were reported in 77.7, 80.2 and 72.0% of participants on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. Confirmed hypoglycaemic adverse events (glucose ≥ 3.9 mmol/l and/or event requiring assistance) were reported in 3.4, 4.1 and 4.2% of participants in these groups, respectively. Conclusions In people with Type 2 diabetes, empagliflozin 10 mg and 25 mg given as add-on to metformin for 76 weeks were well tolerated and led to sustained reductions in HbA1c, weight and systolic blood pressure. [ABSTRACT FROM AUTHOR]

Aims To analyse blood glucose control according to continuous glucose monitoring use in data from the CareLink™ database, and to identify factors associated with continuation of sensor use during sensor-augmented pump therapy. Methods The analysis used data from 10 501 people with Type 1 and 2 diabetes mellitus, of whom 7916 (61.7%) had used glucose sensors for = 15 days during any 6-month period over a 2-year observation period. Data were analysed according to the extent of sensor use (< 25%, 25-49%, 50-74% and = 75% of the time). Time to discontinuation of sensor use was also analysed in new users of glucose sensors. Results Compared with patients in the lowest sensor usage group and non-users, the highest glucose sensor usage group had significantly (P < 0.0001) lower mean blood glucose and blood glucose sd, were more likely to achieve a mean blood glucose concentration < 8.6 mmol/l, (odds ratio 1.5, 95% CI 1.3-1.7; P < 0.0001), and had 50% fewer hypoglycaemic (blood glucose concentration < 2.8 mmol/l) episodes. Among new users, sensor use during the first month of therapy was an important predictor of subsequent discontinuation. Lack of full reimbursement was also significantly associated with early discontinuation, whereas measures of glycaemic control were predictive of discontinuation during long-term treatment. Conclusions The use of continuous glucose monitoring was significantly associated with reductions in hypoglycaemia and improved metabolic control during insulin pump therapy. Sensor use during the first month was strongly associated with long-term adherence; patient education and training may be helpful in achieving this. [ABSTRACT FROM AUTHOR]

Aim To examine prescribing practices and predictors of glucose-lowering therapy within the first year following diagnosis of Type 2 diabetes mellitus in a clinical care setting. Methods We followed people enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort from outpatient hospital clinics and general practices throughout Denmark in 2010-2013. We used Poisson regression to compute age- and gender-adjusted risk ratios (RRs). Results Among 1158 new Type 2 diabetes mellitus patients, 302 (26%) did not receive glucose-lowering therapy within the first year, 723 (62%) received monotherapy [685 (95%) with metformin], and 133 (12%) received more than one drug. Predictors of receiving any vs. no therapy and combination vs. monotherapy were: age < 40 years [RR: 1.29 (95% CI: 1.16-1.44) and 3.60 (95% CI: 2.36-5.50)]; high Charlson Comorbidity Index [RRs: 1.20 (95% CI: 1.05-1.38) and 2.08 (95% CI: 1.16-3.72)]; central obesity [RRs: 1.23 (95% CI: 1.04-1.44) and 1.93 (95% CI: 0.76-4.94)]; fasting blood glucose of ≥ 7.5 mmol/l [RRs: 1.25 (95% CI: 1.10-1.42) and 1.94 (95% CI: 1.02-3.71)]; and HbA1c = 59 mmol/mol (≥ 7.5%) [RR: 1.26 (95% CI: 1.20-1.32) and 2.86 (95% CI: 1.97-4.14)]. Weight gain = 30 kg since age 20, lack of physical exercise and C-peptide of < 300 pmol/l also predicted therapy. Conclusions Comorbidity, young age, central obesity and poor baseline glycaemic control are important predictors of therapy one year after Type 2 diabetes mellitus debut. [ABSTRACT FROM AUTHOR]

Aim To explore the role of early pregnancy health-related quality of life, anxiety, depression and locus of control for pregnancy outcome in women with pregestational diabetes. Methods This was a cohort study of 148 pregnant women with pregestational diabetes (118 with Type 1 diabetes and 30 with Type 2 diabetes), who completed three internationally validated questionnaires: the 36-item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy outcomes were preterm delivery (< 37 weeks) and large for gestational age infants (birth weight > 90th percentile). Differences between groups in the questionnaires were analysed using an unpaired t-test. Results Women with preterm deliveries ( n = 28) had lower (i.e. worse) mean ( sd) quality-of-life scores for the two 36-item Short-Form Health Survey scales, Role-Emotional [58.3 (38.1) vs. 82.9 (31.3); P = 0.0005] and Mental Health [67.7 (20.4) vs. 75.2 (15.8), P = 0.04], and a lower score for the 36-item Short-Form Health Survey scale Mental Component Summary (42.8 (13.1) vs. 48.8 (9.7), P = 0.03) in early pregnancy, compared with women with term deliveries. Depression symptoms (Hospital Anxiety and Depression Scale depression score ≥ 8) were more frequent in women with preterm vs. term deliveries (seven (25%) vs. six women (5%); P = 0.003), while levels of anxiety and locus of control were similar in these two groups. No difference in early pregnancy scores for health-related quality of life, anxiety, depression and locus of control were seen in women delivering large or appropriate for gestational age infants. Conclusions Poor mental quality of life and the presence of depressive symptoms in early pregnancy were associated with preterm delivery in women with pregestational diabetes. [ABSTRACT FROM AUTHOR]

Aim To evaluate the sustainability of the benefits of continuous subcutaneous insulin infusion therapy in routine practice in a cohort of adults with diabetes. Methods The clinical records of all adults starting continuous subcutaneous insulin infusion over 12 years at our centre were included in this study. Baseline and mean annual HbA1c levels were recorded. The frequency of mild-to-moderate and severe hypoglycaemia and hypoglycaemia awareness were analysed in a subgroup. Results Adequate data were available from 327 patients, of whom 71% were female. The patients' mean ± sd age was 41 ± 14 years, the mean ± sd (range) follow-up for continuous subcutaneous insulin infusion was 4.3 ± 2.7 (1-12) years. The mean ± sd HbA1c concentration fell by 8 ± 5 mmol/mol (0.7 ± 0.5%) at year 1 [to 63 ± 12 mmol/mol from 70 ± 18 mmol/mol (7.9 ± 1.1% from 8.6 ± 1.6%); P < 0.0005], sustained to year 5. In patients with initial poor control, HbA1c dropped by 12 ± 11 mmol/mol (1.1 ± 1.0%; P < 0.0005) at year 1, sustained to year 6. The percentage of patients with ≥ 5 mild to moderate hypoglycaemic episodes per week fell from 29 to 12% ( n = 163; P = 0.006). In the subgroup ( n = 87; follow-up 2.5 ± mean ± sd 1.1 years), the frequency of severe hypoglycaemia fell from 0.6 ± 1.7 episodes per patient per year to 0.3 ± 0.9 ( P = 0.047). Of 24 patients with impaired awareness of hypoglycaemia (Gold score ≥ 4), the mean ± sd Gold score improved from 4.9 ± 0.9 to 3.8 ± 1.7 ( P = 0.011). Nine people regained awareness. No deterioration in HbA1c was seen in the hypoglycaemia-prone groups. Conclusions The benefits of continuous subcutaneous insulin infusion with regard to improving glycaemic control and reducing hypoglycaemia frequency, along with improvement in hypoglycaemia awareness without deterioration in glycaemic control, can be sustained over several years in clinical practice. [ABSTRACT FROM AUTHOR]

Aim To investigate the associations of self-perceived competence in diabetes management and autonomy support from healthcare providers with diabetes distress in adults with Type 1 diabetes mellitus that is not optimally controlled [HbA1c ≥ 64 mmol/mol (8.0%)]. Methods This cross-sectional study comprised blood sampling and three self-report questionnaires, the Problem Areas in Diabetes scale, the Perceived Competence in Diabetes Scale and a measure of autonomy support by healthcare providers, the Health Care Climate Questionnaire. We fitted blockwise linear regression models to assess the associations between Problem Areas in Diabetes score and the variables of interest (autonomy support and perceived diabetes competence), controlling for clinical and sociodemographic variables. Results Of the study sample [ n = 178; mean age 36.7 (±10.7) years], 31.5% had long-term complications and 43.2% reported elevated (≥40) Problem Areas in Diabetes scores. A significant negative association was found between autonomy support and Problem Areas in Diabetes score (B = -3.61, P = 0.001), indicating that lower autonomy support was associated with greater diabetes distress. When perceived competence was controlled, it mediated the association of autonomy support with diabetes distress, reducing it to non-significance. There was a significant negative association between perceived competence and Problem Areas in Diabetes score (B = -8.89, P < 0.001), indicating that lower perceived competence was associated with greater perceived distress. Conclusions There was an indirect (fully mediated) relationship between autonomy support and diabetes distress; autonomy support was associated with increased perceived competence, which, in turn, was associated with reduced distress. Healthcare providers' communication styles enhancing perceived competence through autonomy support may contribute to effective treatment for people with Type 1 diabetes and suboptimum glycaemic control. [ABSTRACT FROM AUTHOR]

Aim The evidence for self-management programmes in older adults varies in methodological approaches, and disease criteria. Using predetermined methodological criteria, we evaluated the effect of diabetes-specific self-management programme interventions in older adults. Methods The EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from January 1980 to November 2013, as were reference lists from systematic reviews, meta-analyses and clinical practice guidelines. A total of 13 trials met the selection criteria, which included 4517 older adult participants; 2361 participants randomized to a diabetes self-management programme and 2156 to usual care. Results The pooled effect on HbA1c was a reduction of -2 mmol/mol (-0.2%; 95% CI -0.3 to -0.1); tailored interventions [-3 mmol/mol (-0.2%; 95% CI -0.4 to -0.1)] or programmes with a psychological emphasis [-3 mmol/mol (-0.2; 95% CI -0.4 to -0.1)] were most effective. A pooled treatment effect on total cholesterol was a 5.81 mg/dl reduction (95% CI -10.33 to -1.29) and non-significant reductions in systolic and diastolic blood pressure. Conclusions Diabetes self-management programmes for older adults demonstrate a small reduction in HbA1c, lipids and blood pressure. These findings may be of greater clinical relevance when offered in conjunction with other therapies. [ABSTRACT FROM AUTHOR]

Aims To provide a systematic review of the current evidence concerning the diabetes-related outcomes of patients provided with continuous subcutaneous insulin infusion for treating diabetes mellitus while a hospital inpatient. Methods Relevant publications were obtained from MEDLINE and EMBASE databases concerning hospital inpatients with diabetes being treated with continuous subcutaneous insulin infusion. Studies were assessed independently by two reviewers, and data on the following outcomes were extracted: inpatient mortality; clinical complications, e.g. diabetic ketoacidosis; hyperglycaemia; hypoglycaemia; length of hospital stay; mean bedside glucose level; and glucose level on discharge. Obstetric cases were examined separately to look at maternal and neonatal glycaemic outcomes. Results A total of 11 studies met the required criteria and were analysed in detail, 5 of which were predominantly obstetric. No significant complications were reported, with no incidences of death, ketoacidosis or severe hypoglycaemia. Length of hospital stay appeared to be shorter in those patients who remained on continuous subcutaneous insulin infusion, while data on mild hyperglycaemia and hypoglycaemia were inconclusive. Conclusions There are limited data available to form a significant conclusion about the safety of continuous subcutaneous insulin infusion continuation in hospital; however, its use can be justified with the presence of a specialized inpatient diabetes team for advice and support and an alternative treatment regime (e.g. subcutaneous basal bolus) should be accessible if the need were to arise. [ABSTRACT FROM AUTHOR]

Aim To determine whether the low C-peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series ( n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control ( n = 1273), as well as diabetic complications ( n = 324) and presence of hypoglycaemia ( n = 323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset ( P < 0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c ( P < 0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild ( P = 0.049) or moderate ( P = 0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol ( P < 0.0001). Conclusions Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim To provide estimates of the costs of severe and non-severe insulin-related hypoglycaemia in the UK using the Local Impact of Hypoglycaemia Tool. Methods Rates of hypoglycaemia were extracted from the UK Hypoglycaemia Study Group observational study. The costs of severe and non-severe hypoglycaemic episodes in insulin-treated adults with Type 1 and Type 2 diabetes were estimated from UK data sources. The rates and costs were then applied to specific populations to give an estimate of the cost of insulin-related hypoglycaemia for the UK, a specific locality, or a user-defined population. User-specific rates and costs could also be applied. Results The estimated cost of a hypoglycaemic episode can range from as much as £2,152 for severe episodes (for which the patient is admitted to hospital) to as little as £1.67 for non-severe episodes. With a UK population of 64.1 million, the total estimated cost of managing insulin-related hypoglycaemia is £468.0 m per year (£295.9 m for severe episodes, £172.1 m for non-severe episodes). On a local health economy level, using a hypothetical general population of 100 000, the total cost of managing insulin-related hypoglycaemia is estimated to be £730,052 per year (£461,658 for severe and £268,394 for non-severe episodes). Conclusions The Local Impact of Hypoglycaemia Tool highlights the economic burden of insulin-related hypoglycaemia. Non-severe episodes are often overlooked because of their low individual cost, but their high frequency makes the cumulative cost substantial. The Local Impact of Hypoglycaemia Tool also shows clinicians and budget-holders the economic impact of lower rates of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aims To investigate the usefulness of the additional measurement of HbA1c, compared with performing only the oral glucose tolerance test ( OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. Methods All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c, according to American Diabetic Association 2010 criteria. Results Based on OGTT criteria alone, 3.5% of the study cohort ( N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c, in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia ( N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index ( HOMA- IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia ( N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance ( N = 249; all P < 0.01). Conclusion The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention. [ABSTRACT FROM AUTHOR]

Aims To develop and validate the Diabetes Family Impact Scale, a scale to measure the impact of diabetes on families. Methods The Diabetes Family Impact Scale was developed by an iterative process, with input from multidisciplinary diabetes providers and parents of children with Type 1 diabetes. The psychometric properties of the Diabetes Family Impact Scale were assessed in parents of children with Type 1 diabetes. This assessment included internal consistency, convergent validity and exploratory factor analysis. Results Parents ( n = 148) of children (mean ± sd age 12.9 ± 3.3 years) with Type 1 diabetes (mean ± sd duration 6.2 ± 3.6 years) completed the 15-item Diabetes Family Impact Scale. After eliminating one item, the 14-item measure demonstrated good internal consistency (Cronbach's α = 0.84). Correlations between the Diabetes Family Impact Scale and measures of parent diabetes burden ( r = 0.48, P < 0.0001), stressful life events ( r = 0.28, P = 0.0007), and child's quality of life ( r = -0.52 and -0.54, P < 0.0001 for generic and diabetes-specific quality of life, respectively) supported the convergent validity of the instrument. Factor analysis identified four factors corresponding to the four survey domains (school, work, finances and family well-being). Conclusions The Diabetes Family Impact Scale measures diabetes-specific family impacts with good internal consistency and convergent validity and may be a useful tool in clinical and research settings. [ABSTRACT FROM AUTHOR]

Aim To investigate the association between pulse pressure and risk of hospitalization for cardiovascular events among people with Type 2 diabetes. Methods A population-based case-control study was carried out using data from medical databases. A total of 588 people with Type 2 diabetes from 18 general practices in Cambridgeshire recorded a first hospitalization for a cardiovascular event between 2009 and 2011, and a total of 2920 age-matched, gender-matched and practice-matched control subjects with Type 2 diabetes were selected based on risk-set sampling. Pulse pressure was assessed before admission in 2008-2009. Further dose-response relationships between pulse pressure and risks were explored using spline models. Results There was a non-linear relationship between pulse pressure and the risk of hospitalization for a cardiovascular event ( P < 0.001 for linearity test). The pulse pressure associated with the lowest risk of hospitalization for a cardiovascular event was 61 (95% CI 57-63) mmHg. Conclusion In people with Type 2 diabetes, pulse pressure is a good predictor of risk of hospitalization for cardiovascular events. The risk is lowest with a pulse pressure of 57-63 mmHg. [ABSTRACT FROM AUTHOR]

Aims To determine prevalence and incidence estimates for clinically recognized cases of Type 1 diabetes from the Life For a Child Program ( LFAC) with onset < 26 years in six representative districts, and the capital, of Rwanda. Methods Cases were identified from the LFAC registry and visits to district hospitals. Denominators were calculated from district-level population surveys. Period prevalence data were collected from 1 August 2011 to 31 July 2012 and annual incidence rates were calculated, retrospectively, for 2004-2011. Ninety-five per cent confidence intervals (95% CI) were calculated using a Poisson distribution. Results The prevalence of known Type 1 diabetes in seven districts in Rwanda for ages < 26 years was 16.4 [95% CI 14.6-18.4]/100 000 and for < 15 years was 4.8 [3.5-6.4]/100 000. Prevalence was higher in females (18.5 [15.8-21.4]/100 000) than males (14.1 [11.8-16.7]/100 000; P = 0.01) and rates increased with age. The annual incidence rate for those < 26 years was stable between 2007 and 2011 with a mean incidence over that time of 2.7 [2.0-3.7]/100 000 ( < 15 years = 1.2 [0.5-2.0]/100 000). Incidence rates were higher in females than males and peaked in males at ages 17 and 22 years and in females at age 18 years. Conclusions Our report of known Type 1 diabetes cases shows lower incidence and prevalence rates in Rwanda than previously reported in the USA and most African countries. Incidence of recognized cases has increased over time, but has recently stabilized. However, the likelihood of missed cases due to death before diagnosis and misdiagnosis is high and therefore more definitive studies are needed. [ABSTRACT FROM AUTHOR]

Aims To investigate the occurrence of diabetes-associated autoantibodies and cumulative Type 1 diabetes risk over 18 years in a general population of schoolchildren. Methods In the Karlsburg Type 1 Diabetes Risk Study, 11 986 schoolchildren from north-eastern Germany without a family history of diabetes were screened for glutamic acid decarboxylase antibodies, insulinoma-associated antigen-2 antibodies and insulin autoantibodies by radioligand binding assay. Those children found to be autoantibody-positive were invited to follow-up examinations and HLA-DQB1 genotyping, and were followed for progression to Type 1 diabetes. Results At first follow-up, 119 children had single and 36 children had multiple autoantibodies. Of the multiple autoantibody-positive children, 33 had at least one diabetes-associated HLA-DQB1 allele (*02 and/or *0302). A total of 26 children progressed to Type 1 diabetes, of whom 22 had multiple autoantibodies. The male-to-female ratio of those who progressed to Type 1 diabetes was 1.6. The positive predictive value of multiple autoantibodies was 61.1% compared with only 23.7% for diabetes-associated HLA-DQB1 genotypes among all those who were autoantibody-positive. The cumulative risk was 59.7% after 10 years and 75.1% after 18 years for children with multiple autoantibodies compared with 1.2 and 22.6%, respectively, for children with single autoantibodies ( P<0.001). Among the three examined autoantibodies, insulinoma-associated antigen-2 antibodies conferred the highest risk. Conclusions The diabetes risk in schoolchildren with multiple autoantibodies was similar to the risk reported in other studies for genetically preselected probands; thus, a combined autoantibody-based screening could effectively identify at-risk individuals from the general population for future intervention trials. [ABSTRACT FROM AUTHOR]

Aim This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating ( DAFNE) programme for Type 1 diabetes mellitus. Method Retrospective analysis of data from 892 DAFNE participants from 11 UK centres. Results Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c, age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c, the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110). Conclusion After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c, independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups. [ABSTRACT FROM AUTHOR]