Diabetic Medicine

• A practical framework for encouraging and supporting positive behaviour change in diabetes
  A wide range of diabetes-directed interventions – including novel medications, devices and comprehensive education programmes – have been shown to be effective in clinical trials. But in the real world of diabetes care their efficacy is often dependent upon on how well a clinician is able to support personal engagement and motivation of the person with diabetes to use these new tools and knowledge consistently, and as directed . Although many person-centred motivational and behavioural strategies have been developed, for example, action planning, motivational interviewing and empowerment-based communication, the sheer number and apparent lack of clear differences among them have led to considerable confusion. The primary goal of this review, therefore, is to provide a practical framework that organizes and structures these programmes to enhance their more systematic use in clinical care. Its purpose is to enhance clinician efforts to respectfully encourage and support engagement and motivation for behaviour change in people with diabetes. The three-step framework for organizing and describing the specific clinical processes involved is based on self-determination theory and includes: clinician preparation for a different type of clinical encounter, clinician/person with diabetes relationship building, and clinician utilization of specific behavioural tools. We conclude with practical considerations for application of this framework to the real world of clinical care. This article is protected by copyright. All rights reserved.
• Socio-economic status and risk of gestational diabetes mellitus among Chinese women
  Aims The relationship between socio-economic status and gestational diabetes mellitus has received little attention. The purpose of this study was to investigate the association between socio-economic status and risk of gestational diabetes. Methods Data were obtained from the ongoing Healthy Baby Cohort study in Hubei Province, China, in 2012–2014. Information on educational level and household income was collected using standard questionnaires during face-to-face interviews. Gestational diabetes was defined based on the International Association of Diabetes and Pregnancy Study Group's criteria. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for gestational diabetes in relation to SES. Results Among 6886 participants, 1005 (14.6%) pregnant women were diagnosed with gestational diabetes. Higher educational level was inversely associated with risk of gestational diabetes (OR, 0.74; 95% CI, 0.58, 0.95 for high school and OR, 0.62; 95% CI, 0.50, 0.76 for college or above). After adjustment for potential confounders, the ORs for gestational diabetes were 0.77 (95% CI, 0.59, 1.00) and 0.65 (95% CI, 0.51, 0.83) for women with high school and college or above education, respectively, compared with women with less than high school education. No significant association between household income and gestational diabetes was observed after adjustment for potential confounders. Subgroup analysis showed that the reduced risk of gestational diabetes with higher educational level was more evident among women with a pre-pregnancy BMI < 24 kg/m2 (P for interaction = 0.022). Conclusions Our findings suggested that educational level was a more robust predictor of gestational diabetes than household income among Chinese women. This article is protected by copyright. All rights reserved.
• Successful management of refractory diabetic gastroparesis with long-term Aprepitant treatment
  Background People with gastroparesis who develop treatment-resistant (refractory) disease pose a difficult challenge, especially in the setting of end-stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin-receptor antagonist) is licensed for the short-term treatment of chemotherapy-induced nausea. There is lack of information on its long-term efficacy and safety in people with diabetic gastroparesis. Case report Case 1 was 73-year-old man with Type 2 diabetes of 25 years’ duration and ESRD requiring dialysis. He was referred to our unit as his severe symptoms of gastroparesis had failed to respond to multiple medications and resulted in frequent hospital admissions. Aprepitant, which can be used in ESRD, resulted in significant improvement in his symptoms of nausea and vomiting within weeks, and he remained on this long term (18 months) with continued benefits and had no further gastroparesis-related hospital admissions. Case 2 was a 44-year-old man with Type 1 diabetes of 41 years’ duration with a history of severe hypoglycaemic events that required a pancreas transplant. Despite normoglycaemia, his symptoms of gastroparesis persisted and failed to respond to multiple medications and frequent botulinum toxin injections. He was commenced on aprepitant with significant improvement in symptoms and has remained on treatment for 12 months with sustained benefits. Conclusion We describe two cases in which long-term aprepitant treatment proved effective in alleviating severe symptoms of gastroparesis that had failed to respond to conventional first-line medical treatments. Our cases highlight the need for novel treatments for managing refractory diabetic gastroparesis. This article is protected by copyright. All rights reserved.
• Comparison of different insulin pump makes under routine care conditions in adults with Type 1 diabetes
  Aims To compare long-term HbA1c changes associated with different insulin pumps during routine care in a large cohort of adults with Type 1 diabetes representative of other clinic populations. Methods Observational, retrospective study of 508 individuals starting pump therapy between 1999 and 2014 (mean age, 40 years; 55% women; diabetes duration, 20 years; 94% Type 1 diabetes; median follow-up, 3.7 years). Mixed linear models compared covariate-adjusted HbA1c changes associated with different pump makes. Results The pumps compared were: 50% Medtronic, 24% Omnipod, 14% Roche and 12% Animas. Overall HbA1c levels improved and improvements were maintained during a follow-up extending to 10 years (HbA1c: pre-continuous subcutaneous insulin infusion (pre-CSII) vs. 12 months post CSII, 71 (61, 82) vs. 66 (56, 74) mmol/mol; 8.7 (7.7, 9.6) vs. 8.2 (7.3, 8.9)%; P < 0.0001). The percentage of individuals with HbA1c ≥ 64 mmol/mol (8.0%) reduced from a pre-CSII level of 68% to 55%. After adjusting for baseline confounders, there were no between-pump differences in HbA1c lowering (P = 0.44), including a comparison of patch pumps with traditional catheter pumps (P = 0.63). There were no significant (P < 0.05) between-pump differences in HbA1c lowering in pre-specified subgroups stratified by pre-pump HbA1c, age or diabetes duration. HbA1c lowering was positively related to baseline HbA1c (P < 0.001) and diabetes duration (P = 0.017), and negatively related to the number of years of CSII use (P = 0.024). Conclusions Under routine care conditions, there were no covariate-adjusted differences in HbA1c lowering when comparing different pump makes, including a comparison of patch pumps vs. traditional catheter pumps. Therefore, the choice of CSII make should not be influenced by the desired degree of HbA1c lowering. This article is protected by copyright. All rights reserved.
• European diabetes research and its funding, 2002–2013
  Aim This study examined the outputs of research papers in diabetes from 31 European countries between 2002 and 2013, and their funding. Methods Diabetes research papers in the Web of Science were identified by means of a filter based on journals and title words. For 2009–2013 papers, the funders were coded to show their sector and nationality. Results Europe published 40 547 diabetes papers in the 12 years between 2002 and 2013. Denmark, Sweden and Finland published the most relative to their wealth, but the UK published the most absolutely despite an apparently low burden (as measured by disability-adjusted life years). The largest source of funding was government (30%), followed by the non-profit sector (18%) and industry (13%). The European Commission supported 2.7% of papers, but more in Latvia (33%) and Estonia (16%). Based on an estimated cost per paper of €260 000, the annual research expenditure in Europe was approximately €986 million in 2013. Conclusions The European diabetes burden in disability-adjusted life years increased by one third between 2002 and 2012, but its output of research papers has decreased from 44% to 36% of the world total. This decrease needs to be reviewed in the context of European non-communicable disease research policy. This article is protected by copyright. All rights reserved.
• Annual direct medical costs associated with diabetes-related complications in the event year and in subsequent years in Hong Kong
  Aim To develop models to estimate the direct medical costs associated with diabetes-related complicationsin the event year and in subsequent years. Methods The public direct medical costs associated with 13 diabetes-related complications were estimated among a cohort of 128 353 people with diabetes over 5 years. Private direct medical costs were estimated from a cross-sectional survey among 1825 people with diabetes. We used panel data regression with fixed effects to investigate the impact of each complication on direct medical costs in the event year and subsequent years, adjusting for age and co-existing complications. Results The expected annual public direct medical cost for the baseline case was US$1,521 (95% CI 1,518 to 1,525) or a 65-year-old person with diabetes without complications. A new lower limb ulcer was associated with the biggest increase, with a multiplier of 9.38 (95% CI 8.49 to 10.37). New end-stage renal disease and stroke increased the annual medical cost by 5.23 (95% CI 4.70 to 5.82) and 5.94 (95% CI 5.79 to 6.10) times, respectively. History of acute myocardial infarction, congestive heart failure, stroke, end-stage renal disease and lower limb ulcer increased the cost by 2–3 times. The expected annual private direct medical cost of the baseline case was US$187 (95% CI 135 to 258) for a 65-year-old man without complications. Heart disease, stroke, sight-threatening diabetic retinopathy and end-stage renal disease increased the private medical costs by 1.5 to 2.5 times. Conclusions Wide variations in direct medical cost in event year and subsequent years across different major complications were observed. Input of these data would be essential for economic evaluations of diabetes management programmes. This article is protected by copyright. All rights reserved.
• Fetal overnutrition and offspring insulin resistance and β-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study
  Aims To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. Methods A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes. Results Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of β-cell function (HOMA2-β), P=0.04]. Each 5-kg/m2 increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-β, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (β=1.12, P=0.03) and lower Matsuda index (β=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index. Conclusions Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence. This article is protected by copyright. All rights reserved.
• Predicting inpatient hypoglycaemia in hospitalized patients with diabetes: a retrospective analysis of 9584 admissions with diabetes
  Aims To explore whether a quantitative approach to identifying hospitalized patients with diabetes at risk of hypoglycaemia would be feasible through incorporation of routine biochemical, haematological and prescription data. Methods A retrospective cross-sectional analysis of all diabetic admissions (n=9584) from 1 January 2014 to 31 December 2014 was performed. Hypoglycaemia was defined as a blood glucose level of <4 mmol/l. The prediction model was constructed using multivariable logistic regression, populated by clinically important variables and routine laboratory data. Results Using a prespecified variable selection strategy, it was shown that the occurrence of inpatient hypoglycaemia could be predicted by a combined model taking into account background medication (type of insulin, use of sulfonylureas), ethnicity (black and Asian), age (≥75 years), type of admission (emergency) and laboratory measurements (estimated GFR, C-reactive protein, sodium and albumin). Receiver-operating curve analysis showed that the area under the curve was 0.733 (95% CI 0.719 to 0.747). The threshold chosen to maximize both sensitivity and specificity was 0.15. The area under the curve obtained from internal validation did not differ from the primary model [0.731 (95% CI 0.717 to 0.746)]. Conclusions The inclusion of routine biochemical data, available at the time of admission, can add prognostic value to demographic and medication history. The predictive performance of the constructed model indicates potential clinical utility for the identification of patients at risk of hypoglycaemia during their inpatient stay. This article is protected by copyright. All rights reserved.
• Serious life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes
  Aim It has been suggested that experiencing serious life events may promote Type 1 diabetes in children. Studies in adults are lacking, as are studies on the interaction of life events with genetic factors. We aimed to investigate life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes while taking into account HLA genotype. Methods Analysis was based on 425 incident cases of LADA, 1417 incident cases of Type 2 diabetes and 1702 population-based controls recruited in Sweden between 2010 and 2016. Self-reported information on life events including conflicts, divorce, illness/accidents, death and financial problems experienced during the 5 years preceding diagnosis/index year was used. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated by logistic regression and adjusted for age, sex, BMI, family history of diabetes, smoking, physical activity and education. Results Overall there was no association between experience of any life event and either LADA (OR 0.86, 95% CI 0.68–1.08) or Type 2 diabetes (OR 1.00, 95% CI 0.83–1.21). The results were similar for individual events as well as in separate analysis of men and women. Similar results were seen in more autoimmune LADA (glutamic acid decarboxylase antibodies > median) [OR (any life event) 0.88, 95% CI 0.64–1.21] and in LADA carriers of the high-risk HLA DR4-DQ8 genotype (OR 0.89, 95% CI 0.61–1.29). Conclusions Our findings indicate that experience of a serious life event, including the death of a family member, divorce or financial problems, is not associated with an increased risk of LADA, overall or in genetically susceptible individuals. This article is protected by copyright. All rights reserved.
• Experiences of closed-loop insulin delivery among pregnant women with Type 1 diabetes
  Aims To explore the experiences of pregnant women with Type 1 diabetes, and the relationships between perceptions of glucose control, attitudes to technology and glycaemic responses with regard to closed-loop insulin delivery. Methods We recruited 16 pregnant women with Type 1 diabetes [mean ± sd age 34.1 ± 4.6 years, duration of diabetes 23.6 ± 7.2 years, baseline HbA1c 51±5 mmol/mol (6.8 ± 0.6%)] to a randomized crossover trial of sensor-augmented pump therapy vs automated closed-loop therapy. Questionnaires (Diabetes Technology Questionnaire, Hypoglycaemia Fear Survey) were completed before and after each intervention, with qualitative interviews at baseline and follow-up. Results Women described the benefits and burdens of closed-loop systems during pregnancy. Feelings of improved glucose control, excitement and empowerment were counterbalanced by concerns about device visibility, obsessive data checking and diminished attentiveness to hyper- and hypoglycaemia symptoms. Responding to questionnaires, 80% of participants felt less worry about overnight hypoglycaemia and that diabetes ‘did not run their lives’; however, 45% reported that closed-loop increased time thinking about diabetes, and 33% felt it made sleep and preventing hyperglycaemia more problematic. Women slightly overestimated their glycaemic response to closed-loop therapy. Most became more positive in their technology attitudes throughout pregnancy. Women with more positive technology attitudes had higher degrees of overestimation, and poorer levels of glycaemic control. Conclusions Women displayed complex psychosocial responses to closed-loop therapy in pregnancy. Perceptions of glycaemic response may diverge from biomedical data. This article is protected by copyright. All rights reserved.
• Consideration of the presence of inflammation is essential for interpretation of serum micronutrient results
  It was with great interest I read the recent contribution by Christie-David and Gunton, ‘Vitamin C deficiency and diabetes mellitus – easily missed?’ [1], outlining their retrospective cohort study in 11 patients with poorly healing foot ulcers in the setting of diabetes mellitus. Their findings suggest previously unrecognized vitamin C deficiency may have been a contributing factor to the ulcers that were being treated in their clinic; a hypothesis supported by the healing reported to occur within 3 weeks of the commencement of vitamin C replacement [1]. This article is protected by copyright. All rights reserved.
• Behavioural implications of traditional treatment and closed-loop automated insulin delivery systems in Type 1 diabetes: applying a cognitive restraint theory framework
  As the prevalence of obesity in Type 1 diabetes rises, the effects of emerging therapy options should be considered in the context of both weight and glycaemic control outcomes. Artificial pancreas device systems will ‘close the loop’ between blood glucose monitoring and automated insulin delivery and may transform day-to-day dietary management for people with Type 1 diabetes in multiple ways. In the present review, we draw directly from cognitive restraint theory to consider unintended impacts that closed-loop systems may have on ingestive behaviour and food intake. We provide a brief overview of dietary restraint theory and its relation to weight status in the general population, discuss the role of restraint in traditional Type 1 diabetes treatment, and lastly, use this restraint framework to discuss the possible behavioural implications and opportunities of closed-loop systems in the treatment of Type 1 diabetes. We hypothesize that adopting closed-loop systems will lift the diligence and restriction that characterizes Type 1 diabetes today, thus requiring a transition from a restrained eating behaviour to a non-restrained eating behaviour. Furthermore, we suggest this transition be leveraged as an opportunity to teach people lifelong eating behaviour to promote healthy weight status by incorporating education and cognitive reappraisal. Our aim was to use a transdisciplinary approach to highlight critical aspects of the emerging closed-loop technologies relating to eating behaviour and weight effects and to promote discussion of strategies to optimize long-term health in Type 1 diabetes via two key outcomes: glycaemic control and weight management. This article is protected by copyright. All rights reserved.
• Racial and ethnic differences among children with new-onset autoimmune Type 1 diabetes
  Aim To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes. Methods We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.7 (0.3–18.1) years, the mean (sd) BMI percentile was 69.7 (25.4) and 48.3% of the cohort were girls. The cohort comprised 57.3% non-Hispanic white, 20.5% Hispanic and14.8% African-American children, and 7.4% were of other, mixed or unknown race. Results The Hispanic subgroup, compared with non-Hispanic white subgroup, had a higher mean (sd) C-peptide level [0.82 (1.62) vs 0.55 (0.47) ng/ml; P=0.004), and a greater proportion of children with elevated BMI (overweight or obesity; 49.6% vs 32.5%; P<0.001) and diabetic ketoacidosis (51.8% vs 38.2%; P=0.006). The African-American group had a higher mean (sd) glucose level [24.4 (12.8) vs 21.4 (10.7) mmol/l; P=0.017], a greater proportion of children with ketoacidosis (56.7% vs 38.2%; P=0.001), a greater proportion with elevated BMI (52.9% vs 32.5%; P<0.001), and a lower proportion of children at pre-pubertal stage (49.0% vs 61.6%; P=0.01), and tended to have higher C-peptide levels [0.65 (0.59) vs 0.55 [0.47] ng/ml; P=0.079) compared with the non-Hispanic white children. The differences in C-peptide levels compared with non-Hispanic white children persisted for Hispanic (P=0.01) but not African-American children (P=0.29) after adjustment for age, sex, BMI, ketoacidosis, glucose, Tanner stage and autoantibody number. Conclusion At the onset of paediatric autoimmune Type 1 diabetes, Hispanic, but not African-American children had higher C-peptide levels, after adjustment for potential confounders, compared with non-Hispanic white young children. These findings suggest that ethnicity may contribute to the heterogeneity of Type 1 diabetes pathogenesis, with possible implications for intervention. This article is protected by copyright. All rights reserved.
• Markedly increased incidence of critical illness in adults with Type 1 diabetes
  Aims To compare the incidence of and mortality after intensive care unit admission in adults with paediatric-onset Type 1 diabetes vs the general population. Methods Using population-based administrative data from Manitoba, Canada, we identified 814 cases of paediatric-onset Type 1 diabetes, and 3579 general population controls matched on age, sex and region of residence. We estimated the incidence of intensive care unit admission in adulthood, and compared the findings between populations using incidence rate ratios and multivariable Cox proportional hazards regression, adjusting for age, sex, comorbidity and socio-economic status. We estimated age- and sex-standardized mortality rates after intensive care unit admission. Results Between January 2000 and October 2009, the average annual incidence of intensive care unit admission among prevalent cohorts was 910 per 100 000 in the Type 1 diabetes population, and 106 per 100 000 in matched controls, an eightfold increased risk (incidence rate ratio 8.6; 95% CI 5.5, 14.0). The adjusted risk of intensive care unit admission was elevated to a greater extent among women with Type 1 diabetes compared with matched women (hazard ratio 14.7; 95% CI 7.2, 29.4) than among m en with Type 1 diabetes compared with matched men (hazard ratio 4.92; 95% CI 10.3, 2.36) The most common reasons for admission in the diabetes cohort were diabetic ketoacidosis, infection and ischaemic heart disease. At 30%, 5-year mortality was higher in the diabetes cohort than in the matched cohort (relative risk 5.7; 95% CI 1.2, 8.9). Conclusions Compared with the general population, the risk of intensive care unit admission was higher in adults with paediatric-onset Type 1 diabetes, and mortality after admission was also higher. This article is protected by copyright. All rights reserved.
• Treatment by a moisturizer of xerosis and cracks of the feet in men and women with diabetes: a randomized, double-blind, placebo-controlled study
  Aim To evaluate a moisturizer containing urea, glycerine and petrolatum for healing deep open fissures on the feet of people with diabetes. If left untreated, open fissures, an entry point for bacteria, can lead to infection, ulceration and further complications. Methods This randomized, double-blind, multicentre study at 19 hospitals, general practices and diabetologists in France and Belgium included participants with diabetes and a deep open target fissure on their heel. Participants were randomized to test cream or placebo (1 : 1) for 4 weeks. Complete target fissure healing after 4 weeks (primary criterion) and 2 weeks, target fissure closure, overall fissure healing and xerosis were assessed. Results Some 167 participants were randomized (80 to test cream; 87 to placebo); all were included in the efficacy analyses. The percentage of participants with complete target fissure healing after 4 weeks was higher with test cream than placebo (46.3% vs. 33.3%): the difference did not reach statistical significance (P = 0.088). Fewer participants still had a deep open target fissure with test cream than placebo, the difference was statistically significant and clinically relevant after 2 (24.7% vs. 42.7%, P = 0.027) and 4 weeks (6.4% vs. 24.1%, P = 0.002). The difference in overall fissure healing between test cream and placebo was significant (P < 0.001) and test cream resulted in greater xerosis improvement (P < 0.001 and P = 0.002 at 2 and 4 weeks, respectively). Conclusion The activity of the test cream for treating feet fissures of people with diabetes was confirmed by an improvement in open fissure healing and xerosis. The cream was well tolerated. This article is protected by copyright. All rights reserved.
• Use of 1-h post-load plasma glucose concentration to identify individuals at high risk of developing Type 2 diabetes
• Fludrocortisone therapy for persistent hyperkalaemia
  Background Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition. Case Report A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5.6 mmol/L, bicarbonate 15 mmol/L, and albumin 30 g/L. Her admission was prolonged, complicated by hospital-acquired sepsis (lower respiratory tract, urinary tract, and infected leg ulcers), poor venous access and severe depression. She had recurrent hyperkalaemia and deteriorating renal function, from presumed Type 4 renal tubular acidosis and excessive fluid losses from leg ulcers. Her renal function recurrently deteriorated, despite conventional treatment methods. After 69 days, she was commenced on fludrocortisone 50 mcg/day. Her renal function and serum potassium stabilized and she was discharged with potassium 4.3 mmol/L, eGFR 42 ml/min, and bicarbonate 23 mmol/L. She has remained stable on this treatment, without requiring further hospital admission for over 6 months, with eGFR 40 ml/min, and potassium 5.5 mmol/L, and albumin 26 g/L. Conclusion This woman was presumed to have Type 4 renal tubular acidosis and recurrent hyperkalaemia due to renal insufficiency, in the context of underlying diabetes and chronic kidney disease, which was poorly responsive to conventional management. There is limited evidence for using fludrocortisone in this setting. Our case suggests that fludrocortisone might offer a novel therapeutic strategy when conventional management is not working.
• Table of Contents 1
• Hyperglycaemia-related complications at the time of diagnosis can cause permanent neurological disability in children with neonatal diabetes
  Background Children with neonatal diabetes often present with diabetic ketoacidosis and hence are at risk of cerebral oedema and subsequent long-term neurological deficits. These complications are difficult to identify because neurological features can also occur as a result of the specific genetic aetiology causing neonatal diabetes. Case reports We report two cases of neonatal diabetes where ketoacidosis-related cerebral oedema was the major cause of their permanent neurological disability. Case 1 (male, 18 years, compound heterozygous ABCC8 mutation) and case 2 (female, 29 years, heterozygous KCNJ11 mutation) presented with severe diabetic ketoacidosis at 6 and 16 weeks of age. Both had reduced consciousness, seizures and required intensive care for cerebral oedema. They subsequently developed spastic tetraplegia. Neurological examination in adulthood confirmed spastic tetraplegia and severe disability. Case 1 is wheelchair-bound and needs assistance for transfers, washing and dressing, whereas case 2 requires institutional care for all activities of daily living. Both cases have first-degree relatives with the same mutation with diabetes, who did not have ketoacidosis at diagnosis and do not have neurological disability. Discussion Ketoacidosis-related cerebral oedema at diagnosis in neonatal diabetes can cause long-term severe neurological disability. This will give additional neurological features to those directly caused by the genetic aetiology of the neonatal diabetes. Our cases highlight the need for increased awareness of neonatal diabetes and earlier and better initial treatment of the severe hyperglycaemia and ketoacidosis often seen at diagnosis of these children.
• Changing paradigms and challenges: evidence on the epidemiological and economic burden of diabetes in Latin America
• Screening for diabetic retinopathy in children and young people in the UK: potential gaps in ascertainment of those at risk
• Response to ‘Early view: an opportunity for enhanced peer review’
• The growth of epidemiology in diabetes research
• Table of Contents 2
• Corrigendum