Diabetic Medicine

• Effect of multiparity and ethnicity on the risk of development of diabetes: a large population-based cohort study
  Aims To investigate the relationship between increasing parity and diabetes in a large, population-based cohort, and to examine if this relationship is different among high-risk ethnic groups. Methods A population-based, retrospective cohort study was performed in 738 440 women aged 18–50 years, who delivered babies in Ontario between 1 April 2002 and 31 March 2011. Diabetes incidence postpartum was calculated for each parity and ethnic group. A multivariable analysis of the effect of parity and ethnicity on the incidence of diabetes was performed using a Cox proportional hazards model, adjusting for confounders. Results The diabetes incidence rate per 1000 person-years was 3.69 in women with 1 delivery, 4.12 in women with 3 deliveries and 7.62 in women with ≥5 deliveries. Women with ≥3 deliveries had a higher risk of developing diabetes compared with women with 1 delivery [adjusted hazard ratios 1.06 (95% CI 1.01–1.11) for 3 deliveries, 1.33 (95% CI 1.25–1.43) for 4 deliveries and 1.53 (95% CI 1.41–1.66) for ≥5 deliveries). A similar rise in risk could be seen in Chinese and South-Asian women, with the most influence in Chinese women [hazard ratio 4.59 (95% CI 2.36–8.92) for ≥5 deliveries]. Conclusions There was a positive and graded relationship between increasing parity and risk of development of diabetes. The influence of parity was seen in all ethnicities. This association may be partly related to increasing weight gain and retention with increasing parity, or deterioration in β-cell function. This merits further exploration.
• External national validation of the Leicester Self-Assessment score for Type 2 diabetes using data from the English Longitudinal Study of Ageing
  Aims To validate the Leicester Self-Assessment score using a representative English dataset for detecting prevalent non-diabetic hyperglycaemia or undiagnosed Type 2 diabetes (defined as HbA1c ≥6.0%) and for identifying those who may go on to develop Type 2 diabetes within 10 years. Methods Data were taken from the English Longitudinal Study of Ageing, a nationally representative dataset of people aged ≥50 years. The area under the receiver–operator curve and performance metrics for the score at the recommended score threshold (≥16), were calculated for the outcomes of HbA1c ≥42 mmol/mol (6.0%) at baseline and self-reported Type 2 diabetes within 10 years in those aged 50–75 years at baseline. Results A total of 3203 individuals had a baseline HbA1c measurement, of whom 247 (7.7%) had an HbA1c concentration ≥ 42 mmol/mol (6.0%). The area under the receiver–operator curve was 69.4% (95% CI 66.0–72.9) for baseline HbA1c ≥42 mmol/mol. A total of 3550 individuals had diabetes status recorded at 10 years, of whom 324 (9.1%) were diagnosed with Type 2 diabetes within this time; the area under the receiver–operator curve for this outcome was 74.9% (95% CI 72.4–77.5). The score threshold of ≥16 had a sensitivity of 89.2% (95% CI 85.3–92.4) and a specificity of 42.3% (95% CI 40.5–44.0) for Type 2 diabetes within 10 years. Conclusions The Leicester Self-Assessment score is validated for use across England to identify people with non-diabetic hyperglycaemia or undiagnosed Type 2 diabetes. Those with a high score are at high risk of developing diabetes in the future.
• Bolusing frequency and amount impacts glucose control during hybrid closed-loop
  Aim To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58–86 mmol/mol (7.5%–10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. Methods Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. Results Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9–10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = –0.21, P = 0.19). Conclusion More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.
• HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes
  Aim Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. Methods People with Type 1 diabetes were identified for inclusion from the Scottish Care Information – Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47-month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. Results Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow-up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25–1.45) over 730 days of follow-up (P < 0.001). Conclusion Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes. This article is protected by copyright. All rights reserved.
• Exploring residual risk for diabetes and microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS)
  Aim Approximately half of the participants in the Diabetes Prevention Outcomes Study (DPPOS) had diabetes after 15 years of follow-up, whereas nearly all the others remained with pre-diabetes. We examined whether formerly unexplored factors in the DPPOS coexisted with known risk factors that posed additional risk for, or protection from, diabetes as well as microvascular disease. Methods Cox proportional hazard models were used to examine predictors of diabetes. Sequential modelling procedures considered known and formerly unexplored factors. We also constructed models to determine whether the same unexplored factors that associated with progression to diabetes also predicted the prevalence of microvascular disease. Hazard ratios (HR) are per standard deviation change in the variable. Results In models adjusted for demographics and known diabetes risk factors, two formerly unknown factors were associated with risk for both diabetes and microvascular disease: number of medications taken (HR = 1.07, 95% confidence intervals (95% CI) 1.03 to 1.12 for diabetes; odds ratio (OR) = 1.10, 95% CI 1.04 to 1.16 for microvascular disease) and variability in HbA1c (HR = 1.02, 95% CI 1.01 to 1.03 for diabetes; OR = 1.06, 95% CI 1.04 to 1.09 for microvascular disease per sd). Total comorbidities increased risk for diabetes (HR = 1.10, 95% CI 1.04 to 1.16), whereas higher systolic (OR = 1.22, 95% CI 1.13 to 1.31) and diastolic (OR = 1.14, 95% CI 1.05 to 1.22) blood pressure, as well as the use of anti-hypertensives (OR = 1.41, 95% CI 1.23 to 1.62), increased risk of microvascular disease. Conclusions Several formerly unexplored factors in the DPPOS predicted additional risk for diabetes and/or microvascular disease – particularly hypertension and the use of anti-hypertensive medications – helping to explain some of the residual disease risk in participants of the DPPOS. (Clinical Trial Registry Nos: DPP NCT00004992 and DPPOS NCT00038727) This article is protected by copyright. All rights reserved.
• Insulin secretion and action in North Indian women during pregnancy
  Aim The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1-h glucose value, in a high-risk Indian population from Punjab. Methods Insulin secretion (HOMA2-B) and insulin action (HOMA2-IR) were assessed in 4665 Indian women with or without gestational diabetes defined by the GDM1999 or adapted GDM2013 criteria. Results Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were independently associated with increased insulin resistance. Conclusions Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more severe impairments of insulin secretion and action.
• Characteristics of people with high visit-to-visit glycaemic variability in Type 2 diabetes
  Aims Increased visit-to-visit glycaemic variability is independently associated with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient characteristics associated with raised visit-to-visit glycaemic variability in people with Type 2 diabetes. Methods A case–control study was conducted to establish associations between HbA1c variability and clinical covariates in 10 130 people with Type 2 diabetes. Variability was calculated by two metrics [sd and coefficient of variation (CV)] from a minimum of four HbA1c readings obtained over a 4-year period. High and low variability groups were defined as the top and bottom tertile of the sd or CV, and used in logistic regression analyses including a number of clinical and biochemical covariates. The analyses were stratified into low mean (< 53 mmol/mol; 7%) and high mean (≥ 53 mmol/mol; 7%) HbA1c groups. Results Findings were consistent across both HbA1c groups and variability metrics. Treatment, independent of other factors, was the most strongly associated covariate for the risk of high HbA1c variability. A six-fold increased risk was observed in the low HbA1c group, between the most and least intense treatment regimens (P < 0.001). Similar findings were present in the high HbA1c group with a three-fold increase in risk (P < 0.001). In addition, male gender, younger age, reduced HDL-cholesterol and increased BMI were all found to be independently associated with raised visit-to-visit glycaemic variability. Conclusions Intensive treatment resulting in low mean HbA1c was associated with marked increase in HbA1c variability. Irrespective of diabetes control, the greatest visit-to-visit variability was observed in young, insulin resistant men.
• Cardiac vagal tone, a non-invasive measure of parasympathetic tone, is a clinically relevant tool in Type 1 diabetes mellitus
  Aims To compare a novel index of parasympathetic tone, cardiac vagal tone, with established autonomic variables and to test the hypotheses that (1) cardiac vagal tone would be associated with established time and frequency domain measures of heart rate and (2) cardiac vagal tone would be lower in people with Type 1 diabetes than in a matched healthy cohort and lower still in people with established neuropathy. Methods Cardiac vagal tone is a validated cardiometrically derived index of parasympathetic tone. It is measured using a standard three-lead electrocardiogram which connects, via Bluetooth, to a smartphone application. A 5-min resting recording of cardiac vagal tone was undertaken and observational comparisons were made between 42 people with Type 1 diabetes and peripheral neuropathy and 23 without peripheral neuropathy and 65 healthy people. In those with neuropathy, 24-h heart rate variability values were compared with cardiac vagal tone. Correlations between cardiac vagal tone and clinical variables were also made. Results Cardiac vagal tone was lower in people with established neuropathy and Type 1 diabetes in comparison with healthy participants [median (interquartile range) linear vagal scale 3.4 (1.6–5.5 vs 7.0 (5.5–9.6); P < 0.0001]. Cardiac vagal tone was positively associated with time (r = 0.8, P < 0.0001) and frequency domain markers of heart rate variability (r = 0.75, P < 0.0001), representing established measures of parasympathetic function. Cardiac vagal tone was negatively associated with age (r=–0.32, P = 0.003), disease duration (r=–0.43, P < 0.0001) and cardiovascular risk score (r=–0.32, P = 0.006). Conclusions Cardiac vagal tone represents a convenient, clinically relevant method of assessing parasympathetic nervous system tone, potentially facilitating the earlier identification of people with Type 1 diabetes who should undergo formal autonomic function testing.
• Table of Contents 1
• Editorial Board
• Combination therapy with multiple oral hypoglycaemic agents together with short-term basal insulin in new-onset Type 2 diabetes mellitus with marked hyperglycaemia
• Aims and Scope
• Glucose-6-phosphate dehydrogenase deficiency induced haemolysis in a woman with newly diagnosed diabetes after normalisation of hyperglycaemia
  Background The association between diabetes and G6PD deficiency is still a matter of debate. Hemolysis due to G6PD deficiency in people with diabetes has been reported, but is uncommon. To date, twenty-three cases have been reported from 12 different countries. Case report We reported a 19-year-old Saudi women newly diagnosed with Type 1 diabetes in whom hemolytic crises occurred soon after normalization of hyperglycemia and revealed a G6PD deficiency. We reviewed the pertinent literature of this phenomenon and discussed the relevant theories. Conclusion We conclude that in order to reduce the risk of hemolysis, in an area with high incidence of G6PD deficiency, screening of the enzyme activity should be considered in newly diagnosed people with diabetes. In case of G6PD deficiency, it is advisable to correct plasma glucose level gradually in order to avoid the rapid decline in glucose availability.
• Table of Contents 2
• Overtreatment of diabetes in older people
• Acceptability of a very-low-energy diet in Type 2 diabetes: patient experiences and behaviour regulation
  Aims To evaluate the acceptability of an 8-week very-low-energy diet for remission of Type 2 diabetes, and to identify barriers and facilitators of adherence and behaviour-regulation strategies used by participants in the Counterbalance study. Methods Eighteen of 30 participants in the Counterbalance study (ISRCTN88634530) took part in semi-structured interviews. Of these, 15 participants were interviewed before and after the 8-week very-low-energy diet intervention. Thematic analysis was used to analyse the narratives. Results The prospect of diabetes remission, considerable weight loss, and long-term health improvement provided participants with substantial initial motivation. This motivation was sustained through the experience of rapid weight loss, improvements in blood glucose levels, social support and increased physical and psychological well-being. Overall, adherence to the very-low-energy diet for 8 weeks was perceived as much easier than anticipated, but required personal effort. Participants addressed challenges by removing food from the environment, planning, avoidance of tempting situations or places, and self-distraction. Weight loss and improvements in blood glucose levels lead to a sense of achievement and improvements in physical and psychological wellbeing. Conclusions Dietary treatment for reversal of Type 2 diabetes is acceptable and feasible in motivated participants, and the process is perceived as highly gratifying. Research outside of controlled trial settings is needed to gauge the generalisability of these findings.
• Levels of wound calprotectin and other inflammatory biomarkers aid in deciding which patients with a diabetic foot ulcer need antibiotic therapy (INDUCE study)
  Aims Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Four inflammatory biomarkers were investigated to develop a composite algorithm for mildly infected diabetic foot ulcers: venous white cell count, C-reactive protein (CRP) and procalcitonin, and a novel wound exudate calprotectin assay. Calprotectin is a marker of neutrophilic inflammation. Methods In a prospective study, people with uninfected or mildly infected diabetic foot ulcers who had not received oral antibiotics in the preceding 2 weeks were recruited from community podiatry clinics for measurement of inflammatory biomarkers. Antibiotic prescribing decisions were based on clinicians’ baseline assessments and participants were reviewed 1 week later; ulcer infection was defined by clinicians’ overall impression from their two assessments. Results Some 363 potential participants were screened, of whom 67 were recruited, 29 with mildly infected diabetic foot ulcers and 38 with no infection. One participant withdrew early in each group. Ulcer area was 1.32 cm2 [interquartile range (IQR) 0.32–3.61 cm2] in infected ulcers and 0.22 cm2 (IQR 0.09–1.46 cm2) in uninfected ulcers. Baseline CRP for mild infection was 9.00 mg/ml and 6.00 mg/ml for uninfected ulcers; most procalcitonin levels were undetectable. Median calprotectin level in infected diabetic foot ulcers was 1437 ng/ml and 879 ng/ml in uninfected diabetic foot ulcers. Area under the receiver operating characteristic curve for a composite algorithm incorporating calprotectin, CRP, white cell count and ulcer area was 0.68 (95% confidence intervals 0.52–0.82), sensitivity 0.64, specificity 0.81. Conclusions A composite algorithm including CRP, calprotectin, white cell count and ulcer area may help to distinguish uninfected from mildly infected diabetic foot ulcers. Venous procalcitonin is unhelpful for mild diabetic foot ulcer infection.
• Proportion of daily capillary blood glucose readings required in the target range for target glycaemic control: shift of focus from target range to proportion in range
  Aim Most guidelines provide people with Type 1 diabetes with pre- and post-meal capillary blood glucose (CBG) targets to achieve optimal glycaemic control. We evaluated the proportion of daily CBG readings between 4 and 10 mmol/l in people achieving different HbA1c levels. Method We analysed CBG data from routine pump/meter downloads from 201 adults treated with continuous subcutaneous insulin infusion (CSII) at a single hospital clinic. Exclusion criteria were CSII < 6 months, < 3 CBG/day, pregnancy, haemoglobinopathy and continuous sensor use. People were categorized into three groups based on HbA1c: < 58 mmol/mol, < 7.5% (n = 58); 58–74 mmol/mol, 7.5–8.9% (n = 107); and ≥ 75 mmol/mol, ≥ 9.0% (n = 36). Results Participants had a mean age of 43 ± 13 years and mean HBA1c of 64 mmol/mol (8.0 ± 1.1%). 47% of people started CSII for raised HbA1c, 25% due to hypoglycaemia and the rest during pregnancy. Downloads contained a mean of 22 ± 6.8 days of data per participant. CBG frequency was similar between the three groups (5.6 ± 2.0, 5.6 ± 1.9 and 5.4 ± 1.2 CBG/day; P = 0.468). The proportion of CBG readings between 4 and 10 mmol/l (72–180 mg/dl) was 57.3 ± 25.4%, 50.6 ± 11.1% and 39.9 ± 16.5% (P < 0.0001); < 4 mmol was 13.8%, 8.8% and 4.4% (P < 0.0001) and > 10 mmol/l was 28.9 ± 16.5%, 40.6 ± 12.1% and 55.6 ± 17.9% (P < 0.0001) in the three groups respectively. Conclusions Participants achieving HBA1c < 58 mmol/mol (< 7.5%) had ~ 60% of CBG readings in range (4–10 mmol/l), with up to 30% of readings > 10 mmol/l. This target of achieving 60% or more readings within target, and being permissive with up to 30% readings > 10 mmol/l may be a novel target for people with diabetes, and may reduce anxiety associated with readings out of range.
• Diabetes and risk of occupational injury: a cohort study
  Aims To investigate if diabetes is associated with a higher risk of occupational (workplace or commuting) injury. Methods Medication data from the Finnish Prescription Register were used to identify diabetes cases in 2004 in a large employee cohort (the Finnish Public Sector study). These data were linked to injury records obtained from the Federation of Accident Insurance Institutions. A total of 1020 diabetes cases (median age 52 years, range 20 to 65 years; 66% women) and their 5234 age- and sex-matched controls were followed up until 2011. Sex-stratified Cox proportional hazards models, adjusting for age, occupational status, obesity and health behaviours, were applied. Because of the small number of men in the cohort, injury types and locations were only examined among women. Results During the median follow-up of 6.7 years, 25% of the participants with diabetes (n=252) and 20% of those without (n=1051) experienced an occupational injury. The association between diabetes and injury was stronger in women than men (P=0.048). Diabetes was associated with a higher risk of workplace (hazard ratio 1.37, 95% CI 1.11 to 1.69) and commuting (hazard ratio 1.36, 95% CI 1.03 to 1.79) injury in women. With regard to different injury types and locations, diabetes was associated with bone fractures, dislocations, sprains and strains, and injuries to upper and lower extremities. In men, there was an association between insulin-treated diabetes and commuting injury (hazard ratio 3.14, 95% CI 1.52 to 6.49). Conclusions Diabetes was associated with workplace and commuting injuries in women. Men with insulin-treated diabetes had a higher risk of commuting injuries.
• The cost of treating diabetic ketoacidosis in the UK: a national survey of hospital resource use
  Aim Diabetic ketoacidosis is a commonly encountered metabolic emergency. In 2014, a national survey was conducted looking at the management of diabetic ketoacidosis in adult patients across the UK. The survey reported the clinical management of individual patients as well as institutional factors that teams felt were important in helping to deliver that care. However, the costs of treating diabetic ketoacidosis were not reported. Methods We used a ‘bottom up’ approach to cost analysis to determine the total expense associated with treating diabetic ketoacidosis in a mixed population sample. The data were derived from the source data from the national UK survey of 283 individual patients collected via questionnaires sent to hospitals across the country. Results Because the initial survey collection tool was not designed with a health economic model in mind, several assumptions were made when analysing the data. The mean and median time in hospital was 5.6 and 2.7 days respectively. Based on the individual patient data and using the Joint British Diabetes Societies Inpatient Care Group guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £2064 per patient (95% confidence intervals: 1800, 2563). Conclusion Despite relatively short stays in hospital, costs for managing episodes of diabetic ketoacidosis in adults were relatively high. Assumptions made in the calculations did not consider prolonged hospital stay due to comorbidities or costs incurred as a loss of productivity. Therefore, the actual costs to the healthcare system and society in general are likely to be substantially higher.
• Keeping safe. Continuous glucose monitoring (CGM) in persons with Type 1 diabetes and impaired awareness of hypoglycaemia: a qualitative study
  Aim To further our understanding of individual use and experience of continuous glucose monitoring (CGM) in adults with Type 1 diabetes and impaired awareness of hypoglycaemia, we conducted a qualitative study supplementary to a randomized controlled trial, using semi-structured interviews. Methods Twenty-three participants of the IN CONTROL trial were interviewed within 4 weeks after the last study visit. The interview centred around experiences of CGM, taking into account the person's expectations prior to the trial. The interview was semi-structured, using open-ended questions and, if needed, prompts were offered to elicit further responses. Using thematic analysis, the interview transcripts were coded independently by three members of the research team. The consolidated criteria for reporting qualitative research (COREQ) were followed. Results Overall, CGM was experienced as helpful in gaining more insight into glucose variability, and temporarily improved sense of control, reduced distress and made participants less dependent on others. However, some participants experienced confrontation with CGM output as intrusive, while some reported frustration due to failing technique and difficulty trusting the device. Participants reported active and passive self-management behaviours mirroring individual differences in attitudes and coping styles. Conclusions In adults with Type 1 diabetes at risk of recurrent hypoglycaemia due to impaired awareness of hypoglycaemia, CGM use enhances a sense of control and safety for most, but not all. Future studies should further explore differential use of CGM in this population in the context of active and passive self-management styles.
• Predictors of early renal function decline in adults with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes and the Pittsburgh Epidemiology of Diabetes Complications studies
  Aim Diabetic kidney disease is one of the leading complications of Type 1 diabetes, but its prediction remains a challenge. We examined predictors of rapid decline in estimated GFR (eGFR) in two Type 1 diabetes cohorts: the Coronary Artery Calcification in Type 1 Diabetes (CACTI) and the Pittsburgh Epidemiology of Diabetes Complications (EDC). Methods A select subset of participants (CACTI: n = 210 and EDC: n = 98) diagnosed before 17 years of age with Type 1 diabetes duration ≥ 7 years, and follow-up data on eGFR by CKD-EPI creatinine for up to 8 years were included in the analyses. Early renal function decline was defined as annual decline in eGFR ≥ 3 ml/min/1.73 m2, and normal age-related decline as eGFR ≤ 1 ml/min/1.73 m2. Parallel logistic regression models were constructed in the two cohorts. Results Early renal function decline incidence was 36% in CACTI and 41% in EDC. In both cohorts, greater baseline eGFR (CACTI: OR 3.12, 95% CI 1.97–5.05; EDC: OR 1.92, 95% CI 1.17–3.15 per 10 ml/min/1.73 m2) and log albumin-to-creatinine (ACR) (CACTI: OR 3.24, 95% CI 1.80–5.83; EDC: OR 1.87, 95% CI 1.18–2.96 per 1 unit) predicted greater odds of early renal function decline in fully adjusted models. Conversely, ACE inhibition predicted lower odds of early renal function decline in women in CACTI, but similar relationships were not observed in women in EDC. Conclusions A substantial proportion of people with Type 1 diabetes in the EDC and CACTI cohorts experienced early renal function decline over time. ACE inhibition appeared to be protective only in women in CACTI where the prevalence of its use was twofold higher compared with the EDC.
• Sleep duration and progression to diabetes in people with prediabetes defined by HbA1c concentration
  Aims To evaluate the association between sleep duration and the risk of progression to diabetes among people with prediabetes, defined by HbA1c values. Methods We conducted a cohort study in 17 983 adults who underwent health check-up examinations, including assessments of sleep duration and quality. Diabetes was defined as either HbA1c ≥48 mmol/mol (6.5%), or the use of antidiabetic medication. Time-dependent proportional hazards models were used to evaluate the association between sleep duration and the risk of progression to diabetes. Results During 31,582 person-years of follow-up, 664 incident cases of diabetes were identified; the incidence rate was 21.0 per 1000 person-years. The multivariate adjusted hazard ratios for progression to diabetes in people with sleep durations of ≤5, 6 and ≥8 h compared with 7 h were 1.68 (95% CI 1.30–2.16), 1.44 (95% CI 1.17–1.76) and 1.23 (95% CI 0.85–1.78), respectively (P for quadratic trend <0.001). This association was partially mediated by biomarkers of adiposity, fatty liver and insulin resistance. Conclusion In this large study in young and middle-aged adults with prediabetes, we found an association between short sleep duration and the risk of progression to diabetes. Our findings suggest that sufficient sleep duration is important for delaying or preventing the progression of prediabetes to diabetes.
• Efficacy and safety of alirocumab in people with prediabetes vs those with normoglycaemia at baseline: a pooled analysis of 10 phase III ODYSSEY clinical trials
  Aim To assess the lipid-lowering efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in people with hypercholesterolaemia and prediabetes at baseline vs people with normoglycaemia at baseline in a pooled analysis of 10 ODYSSEY phase III trials. Methods People classified as having prediabetes had baseline HbA1c ≥39 mmol/mol (5.7%) and <48 mmol/mol (6.5%), or two baseline fasting plasma glucose values ≥5.6 mmol/l (100 mg/dl) but no more than one fasting plasma glucose value ≥7.0 mmol/l (126 mg/dl), or had specific terms reported in their medical history; people diagnosed with diabetes at baseline were excluded; and the remainder were classified as having normoglycaemia. Participants received alirocumab or control (placebo/ezetimibe) for 24–104 weeks, with maximally tolerated statin in most cases. The primary efficacy endpoint was LDL cholesterol reductions from baseline to week 24 in the intention-to-treat population using the mixed-effect model with a repeated measures approach. Results Reductions in LDL cholesterol from baseline to week 24 with alirocumab were 44.0–61.8% (prediabetes group) and 45.8–59.5% (normoglycaemia group). In both subgroups, LDL cholesterol reductions were generally similar in those with and without baseline triglycerides ≥1.7 mmol/l (150 mg/dl). Alirocumab was not associated with changes in HbA1c or fasting plasma glucose over time in either subgroup (up to 24 months’ follow-up). Adverse event rates were generally similar in those with and without prediabetes. Conclusions Over a mean follow-up of 24–104 weeks, alirocumab treatment resulted in significant LDL cholesterol reductions from baseline that were similar in participants with prediabetes and those with normoglycaemia at baseline, with no effect on glycaemia and a safety profile similar to that of the control. This article is protected by copyright. All rights reserved.
• Self-compassion is associated with optimum self-care behaviour, medical outcomes and psychological well-being in a cross-sectional sample of adults with diabetes
  Aim To investigate the role of self-compassion in diabetes outcomes, a construct which may be relevant to chronic conditions, given its focus on compassion toward oneself, especially in times of difficulty. Methods In this cross-sectional study we collected data online from 310 adults diagnosed with diabetes. The questionnaire measured three primary outcomes: self-management behaviours; HbA1c levels and psychological well-being. Potential predictors were also assessed, including self-compassion, locus of control, social support and demographics. Results Multiple regression analyses showed that self-compassion had the most consistent association with better outcomes, including all forms of self-management behaviour, HbA1c levels and psychological well-being. Self-compassion was independently associated with 55.1% of the variance in well-being. Internal locus of control was also significantly associated with better well-being and HbA1c outcomes. Chance and external locus of control and social support were generally associated with poorer outcomes. Conclusions Higher levels of self-compassion are typically associated with improved self-management behaviour, medical outcomes and psychological well-being in adults with diabetes mellitus. The present findings suggest that self-compassion may be a parsimonious and suitable intervention target. Future interventions and consultations with medical professionals may benefit from fostering self-compassion in adults with diabetes mellitus. This article is protected by copyright. All rights reserved.