Diabetic Medicine

Wiley Online Library : Diabetic Medicine
  • Rituximab for the treatment of type B insulin resistance syndrome: a case report and review of the literature
    Background Type B insulin resistance syndrome is a rare disease characterized by refractory transient hyperglycaemia and severe insulin resistance associated with circulating anti-insulin receptor antibodies. A standardized treatment regimen for type B insulin resistance syndrome has yet to be established. Case report We report the case of a 64-year-old man undergoing haemodialysis for antineutrophil cytoplasmic antibody-associated vasculitis and diabetic nephropathy, who developed rapid onset of hyperglycaemia (glycated albumin 52.1%). Type B insulin resistance syndrome was diagnosed, on the basis of positivity for anti-insulin receptor antibodies and the man's autoimmune history of antineutrophil cytoplasmic antibody-associated vasculitis and idiopathic thrombocytopenic purpura. Although severe hyperglycaemia persisted in spite of corticosteroids and high-dose insulin therapy, rituximab treatment resulted in remarkable improvement of the man's severe insulin resistance and disappearance of anti-insulin receptor antibodies without any adverse effects. Conclusions According to a literature review of 11 cases in addition to the present case, rituximab appears to be a safe and effective strategy for the treatment of corticosteroid-resistant type B insulin resistance syndrome. This article is protected by copyright. All rights reserved.
  • RD Lawrence Lecture 2017 Incretins: the intelligent hormones in diabetes
    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have attracted considerable scientific and clinical interest due largely to their insulin-releasing and glucose-lowering properties. Indeed, GLP-1-based therapies are now key treatment options for many people with diabetes worldwide. In contrast, GIP-based agents have yet to reach the clinic based primarily on the impaired insulinotropic action of GIP observed in people with diabetes. Nevertheless, GIP is a key physiological regulator of insulin secretion and stable forms of GIP show much promise in rodent models to alleviate diabetes–obesity. Recent studies suggest that GIP may have an important role to play in a combination therapeutic approach or bioengineered with other gut peptides. Moreover, recent experimental studies indicate that incretins also exert pleiotropic effects in regions of the brain associated with learning and memory, thereby supporting preclinical data demonstrating that incretin-based drugs improve cognitive function. This review article, based on the RD Lawrence Lecture presented at Diabetes UK Annual Professional Conference (2017), provides a brief overview of incretins with a major focus on GIP, the development of designer GIP analogues, and how these molecules can improve cognition. Thus, incretins can be considered as ‘the intelligent hormones’ and may hold the key to successfully treating the alarming rise in neurodegenerative disorders. This article is protected by copyright. All rights reserved.
  • Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis
    Aims To perform meta-analyses of studies evaluating the risk of pre-eclampsia in high-risk insulin-resistant women taking metformin prior to, or during, pregnancy. Methods A search was conducted of the Medline, EMBASE, Web of Science and Scopus databases. Both randomized controlled trials and prospective observational cohort studies of metformin treatment vs placebo/control or insulin either prior to or during pregnancy were selected. The main outcome measure was the incidence of pre-eclampsia in each treatment group. Results Overall, in five randomized controlled trials comparing metformin treatment (n=611) with placebo/control (n=609), no difference in the risk of pre-eclampsia was found (combined/pooled risk ratio 0.86, 95% CI 0.33–2.26; P=0.76; I2=66%). Meta-analysis of four cohort studies again showed no significant effect (risk ratio 1.21, 95% CI 0.56–2.61; P=0.62; I2=30%). A meta-analysis of eight randomized controlled trials comparing metformin (n=838) with insulin (n=836), however, showed a reduced risk of pre-eclampsia with metformin (risk ratio 0.68, 95% CI 0.48–0.95; P = 0.02; I2=0%). No heterogeneity was present in the metformin vs insulin analysis of randomized controlled trials, whereas high levels of heterogeneity were present in studies comparing metformin with placebo/control. Pre-eclampsia was a secondary outcome in most of the studies. The mean weight gain from time of enrolment to delivery was lower in the metformin group (P=0.05, metformin vs placebo; P=0.004, metformin vs insulin). Conclusions In studies randomizing pregnant women to glucose-lowering therapy, metformin was associated with lower gestational weight gain and a lower risk of pre-eclampsia compared with insulin. This article is protected by copyright. All rights reserved.
  • Could FreeStyle Libre™ sensor glucose data support decisions for safe driving?
    Aim Many countries require individuals with diabetes to adhere to standards regarding blood glucose testing in order to be granted or retain a driving licence. Currently, interstitial glucose results may not be used. The aim of this study was to determine whether interstitial glucose measurements using flash glucose-sensing technology can provide additional information to augment safe driving. Methods Sensor data from two European studies (NCT02232698 and NCT02082184) of the FreeStyle Libre Glucose Monitoring System™ in insulin-treated Type 1 and Type 2 diabetes, 241 and 224 participants respectively, were used to determine the frequency of a low interstitial sensor glucose result (< 3.9 mmol/l) up to 4 h subsequent to a daytime (07:00–21:00 h) capillary blood glucose result ≥ 5 mmol/l. Results Within 4 h of a capillary blood glucose result ≥ 5 mmol/l a sensor glucose result of < 3.9 mmol/l occurred on 22.0% of occasions (2573 of 11 706 blood glucose readings) for those with Type 1 diabetes, and 8.4% of occasions (699/8352) for those with Type 2 diabetes; 13.8% (1610/11 628) and 4.4% (365/8203) within 2 h, and 10.0% (1160/11 601) and 3.1% (254/8152) within 1.5 h. Analysis of sensor glucose results 5–7 mmol/l demonstrated the glucose trend arrow descending on 14.7% (1163/7894, Type 1 diabetes) and 9.4% (305/3233, Type 2 diabetes) of occasions. Conclusions Sensor-based glucose information with directional arrows has the potential to support assessment of safe glucose levels associated with driving and offers distinct advantages over blood glucose testing for individuals with Type 1 and Type 2 diabetes to concord with driving safety standards.
  • Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data
    Aim To evaluate the concordance between data derived from randomized controlled trial (RCT) and real-world estimates of HbA1c and weight change after 24 weeks of initiation of a basal-bolus compared with a premixed insulin regimen in people with Type 2 diabetes. Methods Data eight RCTs were pooled after a systematic review of studies examining basal-bolus (n = 1893) or premixed (n = 1517) regimens. Real-world data were extracted from the UK primary care dataset for people on basal-bolus (n = 7483) or premixed insulin regimens (n=10 744). The mean differences between HbA1c and weight from baseline were calculated using t-tests, while analysis of variance was used to compare the two treatment regimens. Linear regression analyses were used to determine the predictors of this change. Results Both insulin regimens were associated with HbA1c reductions (real-world data –0.28%; RCT data, –1.4%) and weight gain (real-world data, +0.27 kg; RCT data, +2.96 kg) but there were no significant differences between basal-bolus and premixed insulin. Discordances in the pattern of treatment response were observed, however, between real-world and RCT data for both insulin regimens. For any given baseline HbA1c concentration, the change in HbA1c in the RCTs was greater than in real-world conditions and for those with baseline weight above ~60 kg, RCT data showed overall weight gain in contrast to slight weight loss in the real-world population. Lastly, for both randomized controlled trial and real-world populations, while greater baseline weight was associated with reduced response to treatment, the association was much steeper in the RCT than in the real-world population. In addition, greater baseline weight was associated with greater weight reductions in both premixed insulin and basal-bolus insulin regimens, although to a lesser extent with the latter. Conclusion These results highlight specific discrepancies in the HbA1c reduction and weight change in insulin regimen between real world versus RCT populations; with greater reduction in HbA1c and greater increase in weight observed in the RCT population than in the real-world population. Also, the basal-bolus regimens in both real-world and RCT populations showed greater reduction in HbA1c compared to the premix regimen (though more marked in RCTs), while the premix regimen showed greater increase in weight in real-world, as against basal-bolus in the RCT population.
  • High risk of conversion to diabetes in first-degree relatives of individuals with young-onset type 2 diabetes: a 12-year follow-up analysis
    Aim Family history of diabetes is an established risk factor for Type 2 diabetes, but the impact of a family history of young-onset diabetes (onset < 40 years) on future risk of diabetes among first-degree relatives is unclear. In this prospective study, we examined the influence of family history of late- versus young-onset diabetes on the development of diabetes in a young to middle-aged Chinese population. Methods Some 365 siblings identified through probands with Type 2 diabetes and 452 participants from a community-based health awareness project (aged 18–55 years) who underwent metabolic assessment during the period 1998–2002 were followed to 2012–2013 to determine their glycaemic status. Multivariate logistic regression was performed to investigate the association of family history of diabetes presented at different age categories with development of diabetes. Results In this cohort, 53.4% (n = 167) of participants with a family history of young-onset diabetes, 30.1% (n = 68) of those with a family history of late-onset diabetes and 14.4% (n = 40) of those without a family history developed diabetes. Using logistic regression, family history of diabetes presented at ages ≥ 50, 40–49, 30–39 and < 30 years, increased conversion to diabetes with respective odds ratios of 2.4, 5.8, 9.4 and 7.0 (P < 0.001 for all), after adjustment for socio-economic status, smoking, obesity, hypertension and dyslipidaemia. Among participants without diabetes at baseline, risk association of family history of late-onset diabetes with incident diabetes was not sustained, whereas that of family history of young-onset diabetes remained robust on further adjustment for baseline glycaemic measurements. Conclusions First-degree relatives of people with Type 2 diabetes, especially relatives of those with young-onset diabetes, are at high risk for diabetes.
  • Diabetes-related major lower limb amputation incidence is strongly related to diabetic foot service provision and improves with enhancement of services: peer review of the South-West of England
    Aims To investigate the relationship between high diabetes-related lower limb amputation incidence and foot care services in the South-West region of England. Methods The introduction of 10 key elements of foot care service provision in one area of the South-West resulted in stabilization of foot ulcer incidence and sustained reduction in amputation incidence from 2007. Services introduced included administrative support, standardized general practice foot screening, improved community podiatry staffing, hospital multidisciplinary foot clinics, effective care pathways, availability of an orthotist and audit. Peer reviews of the region's diabetes foot care services were undertaken to assess delivery of these service provisions and compare this with major amputation incidence in other regions with data provided by Yorkshire and Humber Public Health Observatory Hospital Episode Statistics. Recommendations were made to improve service provision. In 2015 changes in service provision and amputation incidence were reviewed. Results Initial reviews in 2013 showed that the 3-year diabetes-related major amputation incidence correlated inversely with adequate delivery of diabetes foot care services (P=0.0024, adjusted R2 =0.51). Repeat reviews in 2015 found that two or more foot care service improvements were reported by six diabetes foot care providers, with improvement in outcomes. The negative relationship between major amputation incidence and service provision remained strong both in the period 2012–2015 and in the year 2015 only (P ≤0.0012, adjusted R2 =0.56, and P= 0.0005, R2=0.62, respectively). Conclusions Major diabetes-related lower limb amputation incidence is significantly inversely correlated with foot care services provision. Introduction of more effective service provision resulted in significant reductions in major amputation incidence within 2 years. Failure to improve unsatisfactory service provision resulted in continued high amputation incidence.
  • Focus group study to identify the central facets of fear of hypoglycaemia in people with Type 2 diabetes mellitus
    Aims To determine key worries about hypoglycaemia among insulin-using adults with Type 2 diabetes using a focus group approach. Methods Thirteen focus groups were conducted in three diabetes outpatient care units and one peer support group was set up, in Germany. A total of 64 insulin-dependent adults with Type 2 diabetes (36.5% women, mean age 65.2 ± 11.0 years) discussed their worries about hypoglycaemia. The qualitative results were assigned into thematic categories using a bottom-up coding procedure. Participants completed the Hypoglycaemia Fear Survey and demographic measures were recorded. The results of the Hypoglycaemia Fear Survey were contrasted with the focus group findings to evaluate how accurately the Hypoglycaemia Fear Survey comprehensively captures features of fear of hypoglycaemia in Type 2 diabetes. Results Eight themes were identified: ‘unconsciousness/death’; ‘aloneness/ helplessness’, ‘fear of hurting somebody’; ‘shame’; ‘loss of physical control’; ‘long-term complications’; ‘diabetes self-management issues’; and ‘impaired awareness’. A total of 30 participants (46.9%) scored ≥3 on at least one item of the Hypoglycaemia Fear Survey worry subscale, indicating elevated worries. The Hypoglycaemia Fear Survey comprehensively captured all identified themes. Self-efficacy with regard to diabetes self-management seemed to play an important role in fear of hypoglycaemia in Type 2 diabetes. Conclusions Given that even subclinical worries can have negative effects on quality of life and diabetes self-management, emphasis should be placed on diabetes education; in particular, to help patients to develop self-efficacy concerning diabetes self-management. The Hypoglycaemia Fear Survey comprehensively captures hypoglycaemia worries in Type 2 diabetes. Additional assessment of self-efficacy might be beneficial to identify people at risk of developing hypoglycaemia worries.
  • Characterizing adults with Type 2 diabetes mellitus and intellectual disability: outcomes of a case-finding study
    Aims To report the results of a case-finding study conducted during a feasibility trial of a supported self-management intervention for adults with mild to moderate intellectual disability and Type 2 diabetes mellitus, and to characterize the study sample in terms of diabetes control, health, and access to diabetes management services and support. Methods We conducted a cross-sectional case-finding study in the UK (March 2013 to June 2015), which recruited participants mainly through primary care settings. Data were obtained from medical records and during home visits. Results Of the 325 referrals, 147 eligible individuals participated. The participants’ mean (sd) HbA1c concentration was 55 (15) mmol/mol [7.1 (1.4)%] and the mean (sd) BMI was 32.9 (7.9) kg/m2, with 20% of participants having a BMI >40 kg/m2. Self-reported frequency of physical activity was low and 79% of participants reported comorbidity, for example, cardiovascular disease, in addition to Type 2 diabetes. The majority of participants (88%) had a formal or informal supporter involved in their diabetes care, but level and consistency of support varied greatly. Post hoc exploratory analyses showed a significant association between BMI and self-reported mood, satisfaction with diet and weight. Conclusions We found high obesity and low physical activity levels in people with intellectual disability and Type 2 diabetes. Glycaemic control was no worse than in the general Type 2 diabetes population. Increased risk of morbidity in this population is less likely to be attributable to poor glycaemic control and is probably related, at least in part, to greater prevalence of obesity and inactivity. More research, focused on weight management and increasing activity in this population, is warranted.
  • Systematic review and meta-analysis of the efficacy of interventions for people with Type 1 diabetes mellitus and disordered eating
    Aim To examine the types of interventions currently available for people with Type 1 diabetes mellitus and their effectiveness. Background The prevalence of disordered eating in people with Type 1 diabetes mellitus is twice that in their counterparts without diabetes, and is associated with worse biomedical outcomes and greater mortality. Methods Medline, Embase, PsycINFO, the Cochrane Library, PubMed and OpenGrey databases were searched up to August 2016 to identify studies on interventions in people with Type 1 diabetes-associated disordered eating. For the systematic review, intervention components were identified and their effectiveness was examined. For the meta-analysis, the pooled effect sizes of glycaemic control (HbA1c) between pre- and post-treatment in treatment and comparison groups were calculated using a random effects model. Results Of 91 abstracts reviewed, six studies met the inclusion criteria, of which three had appropriate data for the meta-analysis (n = 118). The pooled effect size was –0.21 95% CI (–0.58 to 0.16; where negative values represent an improvement in HbA1c levels), indicating no statistically significant improvement in the treatment group compared with comparison group. Inpatient therapy appeared to be the most effective treatment, and this had multiple components including cognitive behavioural therapy, psychoeducation and family therapy. Conclusion Limited or no improvement in glycaemic control and disordered eating symptoms was observed in people with Type 1 diabetes-associated disordered eating who were receiving currently available interventions. The present review suggests that developing an intensive intervention with a joint focus on both disordered eating and diabetes management is needed for this complex patient group.
  • Attenuated heart rate recovery predicts risk of incident diabetes: insights from a meta-analysis
    Aims To assess the association between attenuated heart rate recovery, a non-invasive measure of autonomic dysfunction, and risk of diabetes in the general population. Methods Databases were searched for cohort studies up to May 2017 that reported the association of heart rate recovery with the risk of diabetes. The overall hazard ratios for slowest vs fastest heart rate recovery (the referent) and for every 10-beats-per-min decrement in heart rate recovery were calculated using a random effects meta-analysis model. Results Four cohort studies with 430 incident cases of diabetes among a total of 9113 participants during a mean follow-up period of 8.1 years were included. Results showed that the slowest heart rate recovery was associated with a higher risk of diabetes (hazard ratio 1.66, 95% CI 1.16 to 2.38) vs the fastest heart rate recovery, and the hazard ratio of risk of diabetes for every 10-beats-per-min decrement in heart rate recovery was 1.29 (95% CI 1.13 to 1.48). No significant interaction effect was observed regarding the efficacy of 1-min and 2-min heart rate recovery in predicting risk of diabetes (both Pfor interaction >0.60); however, a linear dose–response relationship existed for overall studies and for studies using 1-min heart rate recovery as the exposure (both P >0.60 for non-linearity). Conclusions Attenuated heart rate recovery is associated with an increased risk of diabetes in a dose-dependent manner, and measurement of heart rate recovery is worth recommending as part of diabetes risk assessment in clinical routines. This article is protected by copyright. All rights reserved.
  • Inequalities in glycaemic control, hypoglycaemia and diabetic ketoacidosis according to socio-economic status and area-level deprivation in Type 1 diabetes mellitus: a systematic review
    Aim The aim of this systematic review was to examine the associations of individual-level as well as area-level socio-economic status and area-level deprivation with glycaemic control, hypoglycaemia and diabetic ketoacidosis in people with Type 1 diabetes mellitus. Methods Ovid MEDLINE was searched to identify relevant cohort, case–control or cross-sectional studies published between January 2000 and June 2015. Search results were screened by title, abstract and keywords to identify eligible publications. Decisions on inclusion or exclusion of full texts were made independently by two reviewers. The Newcastle–Ottawa Scale was used to estimate the methodological quality of included studies. Quality assessment and extracted data of included studies were synthesized narratively and reported according to the PRISMA statement. Results Literature search in Ovid MEDLINE identified 1345 eligible studies. Twenty studies matched our inclusion and exclusion criteria. Two articles were additionally identified through hand search. According to the Newcastle-Ottawa Scale, most of the studies were of average quality. Results on associations of socio-economic status and area-level deprivation with glycaemic control and hypoglycaemia were contradictory between studies. By contrast, lower socio-economic status and higher area-level deprivation were associated with a higher risk for diabetic ketoacidosis in all except one study. Conclusions Lower socio-economic status and higher area-level deprivation are associated with a higher risk of experiencing diabetic ketoacidosis in people with Type 1 diabetes mellitus. Access to care for socially deprived people needs to be expanded to overcome impairing effects on the course of the condition and to reduce healthcare disparities. This article is protected by copyright. All rights reserved.
  • Association between HbA1c and peripheral neuropathy in a 10-year follow-up study of people with normal glucose tolerance, impaired glucose tolerance and Type 2 diabetes
    Aims To explore the association between HbA1c and sural nerve function in a group of people with normal glucose tolerance, impaired glucose tolerance or Type 2 diabetes. Methods We conducted a 10-year follow-up study in 87 out of an original 119 participants. At study commencement (2004), 64 men and 55 women (mean age 61.1 years) with normal glucose tolerance (n=39), impaired glucose tolerance (n=29), or Type 2 diabetes (n=51) were enrolled. At the 2014 follow-up (men, n=46, women, n=41; mean age 71.1 years), 36, nine and 42 participants in the normal glucose tolerance, impaired glucose tolerance and Type 2 diabetes categories, respectively, were re-tested. Biometric data and blood samples were collected, with an electrophysiological examination performed on both occasions. Results At follow-up, we measured the amplitude of the sural nerve in 74 of the 87 participants. The mean amplitude had decreased from 10.9 μV (2004) to 7.0 μV (2014; P<0.001). A 1% increase in HbA1c was associated with a ~1% average decrease in the amplitude of the sural nerve, irrespective of group classification. Crude and adjusted estimates ranged from –0.84 (95% CI –1.32, –0.37) to –1.25 (95% CI –2.31, –0.18). Although the mean conduction velocity of those measured at both occasions (n=73) decreased from 47.6 m/s to 45.8 m/s (P=0.009), any association with HbA1c level was weak. Results were robust with regard to potential confounders and missing data. Conclusions Our data suggest an association between sural nerve amplitude and HbA1c at all levels of HbA1c. Decreased amplitude was more pronounced than was diminished conduction velocity, supporting the notion that axonal degeneration is an earlier and more prominent effect of hyperglycaemia than demyelination. 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.
  • Perioperative passport: empowering people with diabetes along their surgical journey
    Aim To determine whether a handheld ‘perioperative passport’ could improve the experience of perioperative care for people with diabetes and overcome some of the communication issues commonly identified in inpatient extracts. Methods Individuals with diabetes undergoing elective surgery requiring at least an overnight stay were identified via a customized information technology system. Those allocated to the passport group were given the perioperative passport before their hospital admission. A 26-item questionnaire was completed after surgery by 50 participants in the passport group (mean age 69 years) and by 35 participants with diabetes who followed the usual surgical pathway (mean age 70 years). In addition, the former group had a structured interview about their experience of the passport. Results The prevalence of those who reported having received prior information about their expected diabetes care was 35% in the control group vs 92% in the passport group (P<0.001). The passport group found the information given significantly more helpful (P<0.001), including the advice on medication adjustment (P=0.008). Furthermore, those with the passport were more involved in planning their diabetes care (P <0.001), less anxious whilst in hospital (P<0.044) and better prepared to manage their diabetes on discharge (P≤0.001). The mean length of hospital stay was shorter in the passport group, although the difference did not reach significance (4.4 vs 6.5 days; P<0.058). Content analysis indicated that the passport was well liked and innovative. Conclusion Our data indicate that the perioperative passport is effective in both informing and involving people in their diabetes care throughout the perioperative period. This article is protected by copyright. All rights reserved.
  • Consideration of the presence of inflammation is essential for interpretation of serum micronutrient results
  • Table of Contents 2
  • A crisis in diabetes research funding
  • Editorial Board
  • Aims and Scope
  • Table of Contents 1
  • Corrigenda
  • Corrigenda
  • 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.
  • Decline of insulin therapy and delays in insulin initiation in people with uncontrolled diabetes mellitus
    Aims To design and validate a natural language processing algorithm to identify insulin therapy decline from the text of physician notes, and to determine the prevalence of insulin therapy decline and its impact on insulin initiation. Methods We designed the algorithm using the publicly available natural language processing platform Canary. We evaluated the accuracy of the algorithm on 1501 randomly selected primary care physicians’ notes from the electronic medical record system of a large academic medical centre. Using the validated language model, we then studied the prevalence of insulin therapy decline between 2000 and 2014. Results The algorithm identified documentation of insulin therapy decline with a sensitivity of 100% (95% CI 82.4–100), a positive predictive value of 95% (95% CI 74.4–99.9), and a specificity of 99.9% (95% CI 99.6–100.0). We identified 3295 insulin-naïve adults with Type 2 diabetes who were recommended insulin therapy; 984 of them (29.9%) initially declined insulin. People with HbA1c ≥ 75 mmol/mol (9.0%) were more likely [766/2239 (34.2%)] to have declined insulin than people with HbA1c 53–63 mmol/mol (7.0–7.9%) and 64–74 mmol/mol (8.0–8.9%; P < 0.0001). Among the people who initially declined but ultimately started insulin [374/984 (38.0%)], mean time to insulin initiation was 790 days. Conclusions Insulin therapy decline is common, potentially leading to progression of hyperglycaemia and a delay in achievement of glycaemic control. Further investigation is needed to determine the reasons, risk factors and long-term outcomes of this important clinical phenomenon.

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