Management of monogenic diabetes in pregnancy: A narrative review.

Pregnancy in women with monogenic diabetes is potentially complex, with significant implications for both maternal and fetal health. Among these, maturity-onset diabetes of the young (MODY) stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice. Each subtype of MODY requires a distinct approach tailored to the pregnancy, diverging from management strategies in non-pregnant individuals. Glucokinase MODY (GCK-MODY) typically does not require treatment outside of pregnancy, but special considerations arise when a woman with GCK-MODY becomes pregnant. The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus. During pregnancy, the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha (HNF1A)-MODY and HNF4A-MODY depends on the mother's specific circumstances and the available expertise. Management of other rarer MODY subtypes is individualized, with decisions made on a case-by-case basis. Therefore, a collaborative approach involving expert diabetes and obstetric teams is crucial for the comprehensive management of MODY pregnancies.

Associations between glucagon prescribing, hospital admissions for hypoglycaemia and continuous glucose monitoring metrics in adults with type 1 diabetes.

AIMS: To assess features associated with glucagon prescribing and hospital admissions with hypoglycaemia in type one diabetes. METHODS: Observational study of 4462 adults. Outcome measures were features associated with glucagon prescriptions and predictors of hospital admissions with hypoglycaemia and high levels of glucagon prescribing. RESULTS: 74 % did not collect any glucagon prescriptions and 2.7 % collected >6 over 3.5 years. Hospital admission with hypoglycaemia (P = 0.032), impaired awareness (P = 0.049) and female sex (P < 0.001) were associated with glucagon collection. More frequent prescribing of glucagon was associated with diabetes duration (P < 0.001) and socioeconomic deprivation (P < 0.001). Higher average glucose (P = 0.047), higher time above 13.9 mM (P = 0.008) and higher SD (P = 0.002) were associated with glucagon prescribing. Diabetes duration (P < 0.001) and HbA1c (P < 0.001) were higher in people with hospitalised hypoglycaemia. Higher time above 13.9 mM (P = 0.004) and SD glucose (P < 0.001) were most clearly associated with hospitalised hypoglycaemia. CONCLUSIONS: A minority of people with type 1 diabetes have access to glucagon suggesting more could be done to better target this treatment. Individuals with risk factors and those with frequent glucagon prescriptions should be identified for interventions known to reduce hypoglycaemia.

Changes in continuous glucose monitoring metrics and predictors of improvement 12 months after conversion from Freestyle Libre to Freestyle Libre 2.

AIMS: We sought to assess whether conversion from Freestyle Libre to Freestyle Libre 2 (with low and high glucose alert functions) was associated with improved glucose metrics. RESEARCH DESIGN AND METHODS: A prospective observational study to assess changes in CGM metrics in 672 adults with type 1 diabetes when converting to Freestyle Libre 2. Secondary outcomes included predictors of reduction in time below range (TBR) and increase in time in range (TIR). RESULTS: TBR fell by a median of 1.0% (IQR -2.7 to 0.3, p < 0.001) after 12 months and TIR decreased by 1.0% (-8.7 to 6.0, p = 0.004). TIR did not fall in people using high glucose alerts (p = 0.353). Average duration of low glucose events (<3.9 mmoL/L) fell by 10 min (-46 to 18, p < 0.001). Significant improvements in TIR (p = 0.029) and time above 13.9 mM (p = 0.002) were observed in those using high glucose alerts. Alert threshold settings were not associated with glycaemic response; however, low alert use was independently associated with a fall in TBR of ≥0.5% (HR 1.9 [95% CI 1.2-3.1], p = 0.009) and high alert use was independently associated with a rise in TIR of ≥5% (HR 1.6 [95% CI 1.0-2.5], p = 0.043) at 12 months. CONCLUSIONS: Conversion to Freestyle Libre 2 was associated with significant improvements in low glucose metrics. Alert function users were more likely to see improvements across all CGM metrics. Challenges remain in encouraging alert use, helping users set optimal alert thresholds and optimizing response to alerts.

Combining serum metabolomic profiles with traditional risk factors improves 10-year cardiovascular risk prediction in people with type 2 diabetes.

AIMS: To identify a group of metabolites associated with incident cardiovascular disease (CVD) in people with type 2 diabetes and assess its predictive performance over-and-above a current CVD risk score (QRISK3). METHODS AND RESULTS: A panel of 228 serum metabolites was measured at baseline in 1066 individuals with type 2 diabetes (Edinburgh Type 2 Diabetes Study) who were then followed up for CVD over the subsequent 10 years. We applied 100 repeats of Cox least absolute shrinkage and selection operator to select metabolites with frequency >90% as components for a metabolites-based risk score (MRS). The predictive performance of the MRS was assessed in relation to a reference model that was based on QRISK3 plus prevalent CVD and statin use at baseline. Of 1021 available individuals, 255 (25.0%) developed CVD (median follow-up: 10.6 years). Twelve metabolites relating to fluid balance, ketone bodies, amino acids, fatty acids, glycolysis, and lipoproteins were selected to construct the MRS that showed positive association with 10-year cardiovascular risk following adjustment for traditional risk factors [hazard ratio (HR) 2.67; 95% confidence interval (CI) 1.96, 3.64]. The c-statistic was 0.709 (95%CI 0.679, 0.739) for the reference model alone, increasing slightly to 0.728 (95%CI 0.700, 0.757) following addition of the MRS. Compared with the reference model, the net reclassification index and integrated discrimination index for the reference model plus the MRS were 0.362 (95%CI 0.179, 0.506) and 0.041 (95%CI 0.020, 0.071), respectively. CONCLUSION: Metabolomics data might improve predictive performance of current CVD risk scores based on traditional risk factors in people with type 2 diabetes. External validation is warranted to assess the generalizability of improved CVD risk prediction using the MRS.

This study looked at whether combining a group of new markers found in the blood (called metabolites) with traditional risk factors (such as high blood pressure and obesity) could more accurately predict how likely people with type 2 diabetes are to develop cardiovascular diseases in the next 10 years. Key findingsTwelve metabolites (including amino acids and lipids) showed strong association with 10-year cardiovascular risk in people with type 2 diabetes, and a metabolites-based risk score (MRS) was created by integrating these metabolites.Combining the MRS with traditional risk factors was better at predicting the risk of a person with T2D for developing cardiovascular diseases within the next 10 years than using traditional risk factors alone.

Risk of dementia associated with body mass index, changes in body weight and waist circumference in older people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: To determine the relationship of dementia with preceding body mass index (BMI), changes in body weight and waist circumference in older people with type 2 diabetes. METHODS: In the Edinburgh Type 2 Diabetes Study (1064 men and women with type 2 diabetes, aged 60-75), body weight, waist circumference and BMI were measured at baseline and after 4 years in a subgroup (n = 821). Percentage body weight and waist circumference change over 4 years were calculated. Data on incident dementia was recorded during a median follow-up time of 10.84 years. Survival models considering a range of co-variables and/or death as a competing risk were used to estimate the risks of dementia associated with each weight-related variable. RESULTS: A total of 105 incident dementia events were recorded. When compared with people in the lowest BMI group (<25 kg/m2 ), risk of dementia was lower in intermediate BMI groups (25-29.9 kg/m2 , HR 0.44, p = 0.002; 30-34.9 kg/m2 , HR 0.41, p = 0.001) and the highest BMI group (≧35 kg/m2 , HR 0.35, p = 0.001). In the weight change subgroup, 78 incident dementia events were recorded between years 4 and 10. Body weight loss over 5% (compared with ≦5%) was associated with higher incidence of dementia (HR 2.06, p = 0.010). The association between waist circumference change and dementia was not significant. CONCLUSIONS/INTERPRETATIONS: Both a lower BMI and weight loss over a period of years are indicative of increased dementia risk for older people with type 2 diabetes, while waist circumference changes may be less informative.

Variation in general practice referral rate to acute medicine services and association with hospital admission. A retrospective observational study.

BACKGROUND: Variation in general practice (GP) referral rates to outpatient services is well described however variance in rates of referral to acute medical units is lacking. OBJECTIVE: To investigate variance in GP referral rate for acute medical assessment and subsequent need for hospital admission. METHODS: A retrospective cohort study of acute medical referrals from 88 GPs in Lothian, Scotland between 2017 and 2020 was performed using practice population size, age, deprivation, care home residence, and distance from hospital as explanatory variables. Patient-level analysis of demography, deprivation, comorbidity, and acuity markers was subsequently performed on referred and clinically assessed acute medical patients (n = 42,424) to examine how practice referral behaviour reflects clinical need for inpatient hospital care. RESULTS: Variance in GP referral rates for acute medical assessment was high (2.53-fold variation 1st vs. 4th quartile) and incompletely explained by increasing age and deprivation (adjusted R2 0.67, P < 0.001) such that significant variance remained after correction for confounders (2.15-fold). Patients from the highest referring quartile were significantly less likely to require hospital admission than those from the third, second, or lowest referring quartiles (adjusted odds ratio 1.28 [1.21-1.36, P < 0.001]; 1.30 [1.23-1.37, P < 0.001]; 1.53 [1.42-1.65, P < 0.001]). CONCLUSIONS: High variation in GP practice referral rate for acute medical assessment is incompletely explained by practice population socioeconomic factors and negatively associates with need for urgent inpatient care. Identifying modifiable factors influencing referral rate may provide opportunities to facilitate community-based care and reduce congestion on acute unscheduled care pathways.

Managing the populations need for urgent medical care is challenge in many healthcare systems and overcrowding of urgent medical services negatively affects patient experience and can affect timely treatment. In the United Kingdom, the primary sources of patients attending for acute medical care are self-attendance to the hospital or by way of referral by a primary care physician (general practitioner). These data for the first time demonstrate high variation in referral rates for acute medical assessment between general practices which is incompletely explained by factors such as the age, deprivation, distance to the hospital or care home residence status of the care home population. Analysis of over 40,000 of these referrals for urgent medical care was subsequently undertaken to further investigate this variation. After adjusting for important clinical factors, patients referred from "high referring" practices were over 50% less likely to require inpatient hospital care than patients from lower referring practices. This suggests that the threshold for referral varies greatly between individual primary care clinicians, practices, or practice populations and many of these patients may have been suitable for less urgent community-based care. Identification of modifiable factors that account for this unexplained variation may facilitate community-based care and improve patient experience by reducing unnecessary attendance and congestion in already busy emergency care services.

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes.

BACKGROUND: Atherosclerotic cardiovascular diseases (CVD) is the leading cause of death in diabetes, but the full range of biomarkers reflecting atherosclerotic burden and CVD risk in people with diabetes is unknown. Metabolomics may help identify novel biomarkers potentially involved in development of atherosclerosis. We investigated the serum metabolomic profile of subclinical atherosclerosis, measured using ankle brachial index (ABI), in people with type 2 diabetes, compared with the profile for symptomatic CVD in the same population. METHODS: The Edinburgh Type 2 Diabetes Study is a cohort of 1,066 individuals with type 2 diabetes. ABI was measured at baseline, years 4 and 10, with cardiovascular events assessed at baseline and during 10 years of follow-up. A panel of 228 metabolites was measured at baseline using nuclear magnetic resonance spectrometry, and their association with both ABI and prevalent CVD was explored using univariate regression models and least absolute shrinkage and selection operator (LASSO). Metabolites associated with baseline ABI were further explored for association with follow-up ABI and incident CVD. RESULTS: Mean (standard deviation, SD) ABI at baseline was 0.97 (0.18, N = 1025), and prevalence of CVD was 35.0%. During 10-year follow-up, mean (SD) change in ABI was + 0.006 (0.178, n = 436), and 257 CVD events occurred. Lactate, glycerol, creatinine and glycoprotein acetyls levels were associated with baseline ABI in both univariate regression [ßs (95% confidence interval, CI) ranged from - 0.025 (- 0.036, - 0.015) to - 0.023 (- 0.034, - 0.013), all p < 0.0002] and LASSO analysis. The associations remained nominally significant after adjustment for major vascular risk factors. In prospective analyses, lactate was nominally associated with ABI measured at years 4 and 10 after adjustment for baseline ABI. The four ABI-associated metabolites were all positively associated with prevalent CVD [odds ratios (ORs) ranged from 1.29 (1.13, 1.47) to 1.49 (1.29, 1.74), all p < 0.0002], and they were also positively associated with incident CVD [ORs (95% CI) ranged from 1.19 (1.02, 1.39) to 1.35 (1.17, 1.56), all p < 0.05]. CONCLUSIONS: Serum metabolites relating to glycolysis, fluid balance and inflammation were independently associated with both a marker of subclinical atherosclerosis and with symptomatic CVD in people with type 2 diabetes. Additional investigation is warranted to determine their roles as possible etiological and/or predictive biomarkers for atherosclerotic CVD.

HbA1c Is Disproportionately Higher in Women and Older People With Type 1 Diabetes Compared With Flash Glucose Monitoring Metrics of Glycemic Control.

AIMS: Discrepancy between HbA1c and glucose exposure may have significant clinical implications. We sought to assess predictors of disparity between HbA1c and flash monitoring metrics and how these relate to microvascular complications. METHODS: We conducted a cross-sectional study of adults with type 1 diabetes (n = 518). We assessed the relationship between clinic HbA1c and flash monitoring metrics, predictors of discrepancy between these measurements, and whether discrepancy was associated with microvascular complications. RESULTS: Actual HbA1c and estimated HbA1c were strongly correlated (r = .779, P < .001). The likelihood of having a higher actual HbA1c than estimated HbA1c was greater with increasing age (OR = 1.055 per year, P < .001) and lower in men (OR = .208, P < .001). HbA1c was significantly lower in men (58 mmol/mol [51-67]) (7.5% [6.8-8.3]) compared to women (61 mmol/mol [54-70], P = .021) (7.7% [7.1-8.6]), despite no significant differences in any flash monitoring metrics. Whereas HbA1c was not different between younger (≤39 years) and older individuals (>39 years) despite significantly higher glucose exposure, in younger people, based on multiple flash monitoring metrics. Having a lower estimated than actual HbA1c was independently associated with a lower prevalence of retinopathy (OR = .55, P = .004). CONCLUSIONS: HbA1c appears to overestimate glucose exposure in women and older people with type 1 diabetes. This has potentially important clinical implications, as is hinted at by the independent relationship with retinopathy prevalence. It may also be of relevance when considering the use of HbA1c for the diagnosis of diabetes.

Substantial HbA1c Reduction Following Intermittent-Scanning Continuous Glucose Monitoring Was Not Associated With Early Worsening of Retinopathy in Type 1 Diabetes.

BACKGROUND: Early worsening of diabetic retinopathy (EWDR) was observed in the intensively treated arm of the Diabetes Control and Complications Trial (DCCT) before long-term benefits accrued. We sought to assess whether there may be an increased risk of EWDR in high-risk individuals following intermittent-scanning continuous glucose monitoring (iscCGM) commencement. METHODS: An observational study of 139 individuals with type 1 diabetes ≥5 years duration and with baseline HbA1c >75 mmol/mol (9.0%). This cohort was stratified by subsequent HbA1c response to iscCGM (best responders and non-responders). Pan-retinal photocoagulation (PRP), worsening retinopathy status and new development of retinopathy were compared between groups. RESULTS: HbA1c change was -23 mmol/mol (IQR -32 to -19) (-2.1% [-2.9 to -1.8]) in responders and +6 mmol/mol (2-12) (+0.6 [0.2-1.1]) in non-responders (P < .001). There was no difference in subsequent PRP between responders (14.1%) and non-responders (10.3%, P = .340). Baseline HbA1c (HR 1.052 per mmol/mol, P = .002) but not response category (HR 1.244, P = .664) was independently associated with the risk of requiring PRP. Worsening of retinopathy was not different between responders (16.9%) and non-responders (20.6%, P = .577), and the same was true with respect to new development of retinopathy (33.3% vs 31.8%, P = .919). CONCLUSIONS: In a cohort enriched for risk of diabetic retinopathy, reduction in HbA1c did not result in an increased risk of PRP, worsening retinopathy, or new development of retinopathy. These findings offer reassurance that substantial reduction in HbA1c is not independently associated with early worsening of diabetic eye disease in iscCGM users.

A study of diabetic ketoacidosis in the pregnant population in the United Kingdom: Investigating the incidence, aetiology, management and outcomes.

AIM: To estimate the incidence of diabetic ketoacidosis (DKA) among pregnant women, describe its clinical features, management and outcomes and identify the risk factors for the condition. METHODS: A national population-based case-control study was conducted in the UK using the UK Obstetric Surveillance System between April 2019 and September 2020 including all pregnant women with DKA irrespective of the level of blood glucose. The incidence rate of DKA in pregnancy was estimated. A case-control analysis limited to women with type 1 diabetes was performed comparing characteristics of women with DKA (cases) to those of women whose pregnancies were not complicated by DKA (controls). RESULTS: In all, 82 women were identified with DKA in pregnancy; 6.3 per 100,000 maternities (95% CI: 5.0-7.9). No maternal deaths occurred, but perinatal mortality was 12/73 (16%) with 11 stillbirths and one neonatal death. DKA episodes mostly occurred in women with type 1 diabetes (85%) and in the 3rd trimester of pregnancy (71%). Episodes were mainly precipitated by infection (21%), vomiting (21%), steroid therapy (13%) and medication errors (10%). Fifteen percent of women had more than one episode of DKA during their pregnancy. Risk factors associated with DKA among women with type 1 diabetes identified through the case-control analysis were the woman and/or partner not being in a paid employment and having at least one microvascular complication of diabetes before pregnancy. CONCLUSION: DKA in pregnancy was associated with high perinatal mortality and was linked with factors related to socio-economic deprivation, mental health problems and long-term difficulties with glycaemic control.

Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes: year 10 follow-up of the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: We aimed to determine the longitudinal association of circulating markers of systemic inflammation with subsequent long-term cognitive change in older people with type 2 diabetes. METHODS: The Edinburgh Type 2 Diabetes Study is a prospective cohort study of 1066 adults aged 60 to 75 years with type 2 diabetes. Baseline data included C-reactive protein, IL-6, TNF-α fibrinogen and neuropsychological testing on major cognitive domains. Cognitive testing was repeated after 10 years in 581 participants. A general cognitive ability score was derived from the battery of seven individual cognitive tests using principal component analysis. Linear regression was used to determine longitudinal associations between baseline inflammatory markers and cognitive outcomes at follow-up, with baseline cognitive test results included as covariables to model cognitive change over time. RESULTS: Following adjustment for age, sex and baseline general cognitive ability, higher baseline fibrinogen and IL-6 were associated with greater decline in general cognitive ability (standardised ßs = -0.059, p=0.032 and -0.064, p=0.018, respectively). These associations lost statistical significance after adjustment for baseline vascular and diabetes-related covariables. When assessing associations with individual cognitive tests, higher IL-6 was associated with greater decline in tests of executive function and abstract reasoning (standardised ßs = 0.095, p=0.006 and -0.127, p=0.001, respectively). Similarly, raised fibrinogen and C-reactive protein levels were associated with greater decline in processing speed (standardised ßs = -0.115, p=0.001 and -0.111, p=0.001, respectively). These associations remained statistically significant after adjustment for the diabetes- and vascular-related risk factors. CONCLUSIONS/INTERPRETATION: Higher baseline levels of inflammatory markers, including plasma IL-6, fibrinogen and C-reactive protein, were associated with subsequent cognitive decline in older people with type 2 diabetes. At least some of this association appeared to be specific to certain cognitive domains and to be independent of vascular and diabetes-related risk factors.

Addition of hyaluronic acid to the FIB-4 liver fibrosis score improves prediction of incident cirrhosis and hepatocellular carcinoma in type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

BACKGROUND: Type 2 diabetes (T2D) is associated with increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC) in people with chronic liver diseases, particularly non-alcoholic fatty liver disease (NAFLD). However, the absolute risk of progression is low. So, it is crucial to accurately identify patients who would benefit most from hepatology referral and intensified management. Current risk-stratification tools are suboptimal and perform worse in people with diabetes. AIMS: To determine whether the addition of complementary biomarker(s) to current NAFLD risk-stratification tools in people with T2D could improve the identification of people who are at increased risk of developing incident cirrhosis or HCC. METHODS: The Edinburgh Type 2 diabetes Study (ET2DS) is a cohort study of men and women with T2D (n = 1066, age 60-75 at baseline). Cases of cirrhosis and HCC were identified over 11 years of follow-up. Biomarkers were measured at baseline and year 1 and association with incident disease was assessed using logistic regression. RESULTS: Of existing risk-stratification scores tested, the Fibrosis-4 (FIB-4) index and the AST:platelet ratio index (APRI) performed best in this cohort. Addition of hyaluronic acid (cut-point ≥ 50  µ  g/L) to FIB-4 (cut-point ≥ 1.3) maintained a false negative rate of ≤25% and reduced the number of people incorrectly identified as "high risk" for incident disease by ∼50%. CONCLUSIONS: The addition of hyaluronic acid to FIB-4 reduced the proportion of people inappropriately identified as "high risk" for development of cirrhosis/HCC in a community population of otherwise asymptomatic people with T2D. These findings require a validation in independent cohorts.

"Please see this man with a 69-year history of hypoglycaemia".

Mutations in the HNF4A gene are associated with hyperinsulinaemic hypoglycaemia in infants, frequently evolving into relative deficiency of insulin in adulthood ---as maturity onset diabetes of the young (MODY). A 69-year-old male with a strong family history of adult-onset diabetes was referred with lifelong hypoglycaemia, found to be due to a pathogenic HNF4A mutation. HbA1c levels were low, continuous glucose monitoring demonstrated frequent low glucose events in the early morning, and he was successfully treated with diazoxide. This case represents a new phenotype of a known mutation associated more commonly with MODY. The same mutation in one family led to profoundly different manifestations. Genetic causes of hyperinsulinaemic hypoglycaemia can present late in life and identifying such cases is important to allow the correct treatment to be established.

Retinal arteriolar tortuosity and fractal dimension are associated with long-term cardiovascular outcomes in people with type 2 diabetes.

AIMS/HYPOTHESIS: Our aim was to determine whether quantitative retinal traits in people with type 2 diabetes are independently associated with incident major cardiovascular events including CHD and stroke. METHODS: A total of 1066 men and women with type 2 diabetes, aged 65-74 years, were followed up over 8 years in the population-based Edinburgh Type 2 Diabetes Study. Using retinal photographs taken at baseline and specialist software, a number of quantitative retinal traits were measured, including arteriolar and venular widths and tortuosity as well as fractal dimension (a measure of the branching pattern complexity of the retinal vasculature network). Incident CHD events occurring during follow-up included fatal and non-fatal myocardial infarction, first episodes of angina and coronary interventions for CHD. Incident cerebrovascular events included fatal and non-fatal stroke or transient ischaemic attack. Cox proportional hazard regression analyses were performed to identify the association of the retinal traits with cardiovascular events in the population with retinal data available (n = 1028). RESULTS: A total of 200 participants had an incident cardiovascular event (139 CHD and 61 cerebrovascular events). Following adjustment for age and sex, arteriolar tortuosity and fractal dimension were associated with cerebrovascular events (HR 1.27 [95% CI 1.02, 1.58] and HR 0.74 [95% CI 0.57, 0.95], respectively), including with stroke alone (HR 1.30 [95% CI 1.01, 1.66] and HR 0.73 [95% CI 0.56, 0.97], respectively). These associations persisted after further adjustment for established cardiovascular risk factors (HR 1.26 [95% CI 1.01, 1.58] and HR 0.73 [95% CI 0.56, 0.94], respectively). Associations generally reduced in strength after a final adjustment for the presence of diabetic retinopathy, but the association of fractal dimension with incident cerebrovascular events and stroke retained statistical significance (HR 0.73 [95% CI 0.57, 0.95] and HR 0.72 [95% CI 0.54, 0.97], respectively). Associations of retinal traits with CHD were generally weak and showed no evidence of statistical significance. CONCLUSIONS/INTERPRETATION: Arteriolar tortuosity and fractal dimension were associated with incident cerebrovascular events, independent of a wide range of traditional cardiovascular risk factors including diabetic retinopathy. These findings suggest potential for measurements of early retinal vasculature change to aid in the identification of people with type 2 diabetes who are at increased risk from stroke.

The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin.

AIMS/HYPOTHESIS: We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). METHODS: This is a retrospective cohort study using the Scottish Care Information - Diabetes database for retinal screening outcomes and HbA1c changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan-Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA1c, blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA1c and change in HbA1c on diabetic retinopathy progression was assessed within CSII and MDI cohorts. RESULTS: CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA1c and higher diastolic BP at baseline. There was a larger reduction in HbA1c at 1 year in those on CSII vs MDI (-6 mmol/mol [-0.6%] vs -2 mmol/mol [-0.2%], p < 0.01). Diabetic retinopathy progression occurred in a smaller proportion of adults following commencement of CSII vs continued MDI therapy over mean 2.3 year follow-up (26.5% vs 18.6%, p = 0.0097). High baseline HbA1c (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA1c at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. CONCLUSIONS/INTERPRETATION: CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA1c. Progression of diabetic retinopathy over 3 years was not associated with a change in HbA1c.

Medullary Thyroid Cancer Patient's Assessment of Quality of Life Tools: Results from the QaLM Study.

BACKGROUND: Medullary thyroid cancer (MTC) is a neuroendocrine tumour and a rare variant of thyroid cancer with different aetiology, presentation and treatment to differentiated thyroid cancer. Currently available thyroid cancer-specific quality of life (QoL) tools focus on issues and treatments more relevant to patients with differentiated thyroid cancer and therefore may not address issues specific to a MTC diagnosis and cancer journey. METHOD: This prospective multicentre randomised study involved 204 MTC patients completing four quality of life questionnaires (QOLQ) and stating their most and least preferred. The questionnaires were a general instrument, the EORTC QLQ-C30, two disease-specific tools, the MD Anderson Symptom Inventory (MDASI) thyroid module and the City of Hope Quality of Life Scale/THYROID (amended) and the neuroendocrine questionnaire, EORTC QLQ-GINET21. Patients were randomised to complete the four questionnaires in one of 24 possible orders and then answered questions about which tool they preferred. The primary outcome measure was patients' preferred QoL instrument for describing their concerns and for facilitating communication with their healthcare professional. Secondary analyses looked at differences between preferred QOLQs amongst patient subgroups (WHO performance status [0 and 1+], disease stage: early [T1-3, N0 or N1A], metastatic [T4, any T N1b] and advanced [any T any N M1], and type of MTC [sporadic and inherited]), identification of MTC patients' least preferred questionnaire and clinicians' views on the QoL tools in terms of their ability to highlight problems not otherwise ascertained by a standard clinical review. RESULTS: No evidence of a difference was observed for most preferred QOLQ (p = 0.650). There was however evidence of a difference in least preferred questionnaire in the cohort of 128 patients who stated their least preferred questionnaire (p = 0.042), with 36% (46/128) of patients choosing the EORTC QLQ-GI.NET21 questionnaire. Subgroup analyses showed that there was no evidence of a difference in patients' most preferred questionnaire in sporadic MTC patients (p = 0.637), patients with WHO PS 0 or 1+ (p = 0.844 and p = 0.423) nor when comparing patients with early, advanced local or metastatic disease (p = 0.132, p = 0.463 and p = 0.506, respectively). Similarly, subgroup analyses on patients' least preferred questionnaires showed no evidence of differences in sporadic MTC patients (p = 0.092), patients with WHO PS 0 or 1+ (p = 0.423 and p = 0.276), nor in early or metastatic disease patients (p = 0.682 and p = 0.345, respectively). There was however some evidence to suggest a difference in least preferred questionnaire in patients with advanced local stage disease (p = 0.059), with 43% (16/37) of these patients choosing the EORTC QLQ-GI.NET21 questionnaire. CONCLUSIONS: MTC patients regardless of their performance status, disease aetiology and disease burden did not express a preference for any one particular questionnaire suggesting any of the tools studied could be utilized in this patient cohort. The least preferred questionnaire being a gastrointestinal NET specific tool suggests that diarrhoea was not a significant symptom and concern for the population studied.