Rates of referable eye disease in the Scottish National Diabetic Retinopathy Screening Programme.

AIMS: Diabetic retinopathy screening aims to detect people at risk of visual loss due to proliferative diabetic retinopathy, but also refers cases of suspected macular oedema (maculopathy). At the introduction of screening, ophthalmology was concerned that referral rates would be unmanageable. We report yield of referable disease by referral reason for the first 5 years of the programme. METHODS: We extracted screening results from a nationwide clinical diabetes database to calculate annual referral rates to ophthalmic clinics. We used logistic regression to examine associations between clinical measures and referable disease. RESULTS: 182 397 people underwent ≥ 1successful retinal screening between 2006 and 2010. The yield of referable eye disease was highest in the first 2 years of screening (7.0% and 6.0%) before stabilising at ∼4.3%. The majority of referrals are due to maculopathy with 73% of referrals in 2010 based on a finding of maculopathy. CONCLUSIONS: The commonest cause for referral is for suspected macular oedema (maculopathy). Referral rates for retinopathy have stabilised, as predicted, at relatively low rates. However, ophthalmology workload continues to rise as new treatment options (ie, monthly intraocular injections) have unexpectedly increased the impact on ophthalmology. A review of the screening referral path for maculopathy may be timely.

Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme.

AIMS/HYPOTHESIS: The aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening. METHODS: This was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy. RESULTS: The study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years. CONCLUSIONS/INTERPRETATION: Transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.

A randomized crossover study to assess the effect of an oat-rich diet on glycaemic control, plasma lipids and postprandial glycaemia, inflammation and oxidative stress in Type 2 diabetes.

AIMS: In the UK, lifestyle intervention is first-line management in Type 2 diabetes. It is unclear what type of diet is most efficacious for improving glycaemic control. This study investigated the effects of an oat-enriched diet on glycaemic control, postprandial glycaemia, inflammation and oxidative stress compared with standard dietary advice. METHODS: In a randomized crossover design, 27 volunteers with Type 2 diabetes, managed on diet and lifestyle only, were observed for two consecutive 8-week periods following either the oat-enriched diet or re-enforced standard dietary advice. Volunteers attended at baseline (habitual intake) and 8 and 16 weeks. Measurements included basic clinical measurements and fasted and postprandial (3-h) glucose and insulin in response to a healthy test meal. Markers of inflammation and oxidative stress, including high-sensitivity C-reactive protein, interleukin 6, interleukin 18, tumour necrosis factor-alpha, adiponectin, thiobarbituric acid reactive substances, oxygen radical antioxidant capacity, oxidized LDL and urinary isoprostanes, were also measured at fasting and in the postprandial period. RESULTS: There were no diet-related effects on glycaemic control or glycaemic or insulinaemic responses to the test meal. Total cholesterol (5.1 ± 1.0 vs. 4.9 ± 0.8 mmol/l, P = 0.019) concentrations declined following the oat-enriched diet compared with standard dietary advice. There was a postprandial decline in adiponectin concentration (P = 0.009), but no effect of dietary intervention. None of the measures of oxidative stress or inflammation were altered by the oat-enriched diet compared with standard dietary advice. CONCLUSION: The oat-enriched diet had a modest impact on lipid lowering, but did not impact on oxidative stress or inflammation in these volunteers with Type 2 diabetes.

Hospitalised hip fracture risk with rosiglitazone and pioglitazone use compared with other glucose-lowering drugs.

AIMS/HYPOTHESIS: Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture in women and men and compared the risk to that found with other drugs used in diabetes. METHODS: Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999-2008. RESULTS: There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28; p = 3 × 10(-5)), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%). CONCLUSIONS/INTERPRETATION: Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.

Inpatient costs for people with type 1 and type 2 diabetes in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.

AIMS/HYPOTHESIS: The rising prevalence of diabetes worldwide has increased interest in the cost of diabetes. Inpatient costs for all people with diabetes in Scotland were investigated. METHODS: The Scottish Care Information-Diabetes Collaboration (SCI-DC), a real-time clinical information system of almost all diagnosed cases of diabetes in Scotland, UK, was linked to data on all hospital admissions for people with diabetes. Inpatient stay costs were estimated using the 2007-2008 Scottish National Tariff. The probability of hospital admission and total annual cost of admissions were estimated in relation to age, sex, type of diabetes, history of vascular admission, HbA(1c), creatinine, body mass index and diabetes duration. RESULTS: In Scotland during 2005-2007, 24,750 people with type 1 and 195,433 people with type 2 diabetes were identified, accounting for approximately 4.3% of the total Scottish population (5.1 million). The estimated total annual cost of admissions for all people diagnosed with type 1 and type 2 diabetes was £26 million and £275 million, respectively, approximately 12% of the total Scottish inpatient expenditure (£2.4 billion). Sex, increasing age, serum creatinine, previous vascular history and HbA(1c) (the latter differentially in type 1 and type 2) were all associated with likelihood and total annual cost of admission. CONCLUSIONS/INTERPRETATION: Diabetes inpatient expenditure accounted for 12% of the total Scottish inpatient expenditure, whilst people with diabetes account for 4.3% of the population. Of the modifiable risk factors, HbA(1c) was the most important driver of cost in type 1 diabetes.

Severe hypoglycaemia during pregnancy in women with Type 1 diabetes is common and planning pregnancy does not decrease the risk.

AIMS: The aim of this study was to identify risk factors for severe hypoglycaemia (SH) in pregnancy in Type 1 diabetes, including associations with pregnancy planning and glycaemic control. METHODS: Clinical data including details of the pregnancy and its outcome, glycaemic control, frequency of SH and evidence of pregnancy planning were collected prospectively as part of a national audit of 160 pregnancies in women with Type 1 diabetes. RESULTS: An episode of SH was experienced by 29.4% of women at some point during the pregnancy, with the percentage of women experiencing SH decreasing from 21.9% in the first trimester to 18.1% in trimester 2 and 10.9% in trimester 3. Longer duration of diabetes was associated with increased frequency of SH during pregnancy (r = 0.191, P = 0.012). A greater fall in glycated haemoglobin (HbA(1c)) between pre-pregnancy and the first trimester was not associated with increased risk of SH in trimester 1. Planned pregnancies had better glycaemic control but higher risk of SH in trimester 1 (P = 0.047). Women with pre-pregnancy retinopathy and current smokers had an increased risk of SH in trimester 3 (P = 0.029, P = 0.033). CONCLUSIONS: SH is common during pregnancy and particularly in the first trimester. Planning pregnancy does not decrease the risk of SH. Improvements in glycaemic control at the start of pregnancy do not appear to increase the risk of SH. Education of women and their partners about the risks of SH and its management is essential when planning pregnancy.

Glycaemic control and body mass index in late-adolescents and young adults with Type 1 diabetes mellitus: a population-based study.

AIMS: Studies of children with diabetes up to the age of 15 years report deteriorating glycaemic control in the early teenage years. The aim was to investigate glycaemia and body mass index in older teenagers and young adults. METHOD: A Scottish, regional, population-based, cross-sectional study of 255 young people (117 female, 138 male) with Type 1 diabetes, aged 15-25 years (mean +/-sd 19.8 +/- 2.8 years, diabetes duration: 8.8 +/- 5.4 years) registered on a diabetes database. Glycaemic control, body mass index (BMI) and insulin regimens were assessed in three age groups [group 1 (n = 96) 15-18 years; group 2 (n = 74) 18.1-22 years; and group 3 (n = 85) 22.1-25 years]. RESULTS: Subjects in the oldest age group had a significantly lower mean HbA(1c) than those in the youngest age group (8.8 +/- 1.7 vs. 9.9 +/- 1.9%; P < 0.001). Mean BMI was higher in group 3 (25.2 +/- 3.4 kg/m(2)) compared with group 1 (23.9 +/- 3.1 kg/m(2); P < 0.001). HbA(1c )levels were higher in the younger subjects and women. Lower HbA(1c) levels were associated with a higher BMI (r = -0.324, P < 0.001) in men only. Overall, 74% took three or more injections a day, of whom 60% were on basal/bolus therapy. The proportion on basal/bolus insulin therapy increased with age and duration of diabetes. CONCLUSION: Compared with adolescents, young adults with Type 1 diabetes have better glycaemic control and higher BMI. This was associated with lower insulin requirements.

Birth weight and maternal glycated haemoglobin in pregnancies complicated by type 1 diabetes.

AIM: To re-examine the relationships between birth weight and maternal glycated haemoglobin (HbAlc) concentration at different time points in pregnancies complicated by pre-gestational type 1 diabetes. METHODS: A dataset was collected prospectively on all deliveries in Scotland to women with pre-gestational type 1 diabetes occurring during two 12 month periods (01/04/98 to 31/03/99 and 01/04/03 to 31/03/04). Relationships between standardised measures of birth weight and HbAlc at each time point were examined using correlation analysis. RESULTS: Standardised birth weights (Z scores) were calculated for 338 singleton live born infants. HbA1c concentrations were available for: 204 women (pre-pregnancy), 297 women (1st trimester), 314 women (2nd trimester) and 303 women (3rd trimester). Standardised birth weight showed a unimodal distribution shifted to the right relative to a reference population (Mean, +1.62 S.D). There was a significant negative correlation between pre-pregnancy HbAlc and birth weight (Spearman's Rho -0.138; p=0.049). CONCLUSIONS: Standardised birth weights of the infants of diabetic mothers are higher than those of a reference population. There is no simple relationship between maternal glycaemic control and birth weight, but the previously described paradoxical inverse relationship between pre-pregnancy glycaemic control and birth weight has been confirmed using a larger dataset.

The relationship between pre-pregnancy care and early pregnancy loss, major congenital anomaly or perinatal death in type I diabetes mellitus.

The relationships between markers of pregnancy planning and pre-pregnancy care and adverse outcomes (early pregnancy loss, major congenital anomaly and perinatal death) were examined in 423 singleton pregnancies in women with pre-gestational type I diabetes mellitus. Pregnancy planning and markers of pre-pregnancy care were associated with reduced risks of adverse pregnancy outcomes. 'Documentation of achievement of an optimal haemoglobin A1c prior to discontinuation of contraception' was the marker associated with the lowest rate of adverse outcome (OR 0.2; 95% CI 0.06-0.67) and might serve as an appropriate definition of pre-pregnancy care for research and audit purposes.

Birthweight and other pregnancy outcomes in a cohort of women with pre-gestational insulin-treated diabetes mellitus, Scotland, 1979-95.

AIMS: To assess pregnancy outcomes, in particular birthweight, in a large population-based cohort of women in Scotland with pre-gestational insulin-treated diabetes mellitus. METHODS: Data about diabetes from the Diabetes UK cohort were linked to data on births from the Scottish Hospital In-Patient Record System. This identified 1112 eligible singleton deliveries during 1979-95 to 706 insulin-treated women. RESULTS: One thousand and eighty-four (97.5%) deliveries resulted in a live-born infant and 28 (2.5%) in a stillbirth. There were 13 (1.2%) neonatal deaths. The mean birthweight of the live-born infants was 3421 g, 1.06 standard deviations greater than that of infants in the Scottish general population after correcting for sex and gestational age. Forty-three per cent of live-born babies in the study were large (> Scottish 90th percentile) and 4% small (< 10th percentile) for their sex and gestational age. Macrosomia, defined as birthweight > or = 4000 g, occurred in 23% live-born babies and its prevalence was significantly inversely related to duration of maternal diabetes. However, the mean birthweight of infants born to mothers with diabetes for 20 or more years was still 0.90 standard deviations greater than in the general population. Prevalence of macrosomia increased with increasing number of previous pregnancies, but was not associated with maternal height or smoking habits. Stillbirth and neonatal death rates were, respectively, 4.7 (95% confidence interval = 3.3, 6.8) and 2.4 (1.4, 4.1), times higher than those in the general population. CONCLUSIONS: The frequency of adverse pregnancy outcomes in women with pre-existing insulin-treated diabetes was much higher than in the Scottish general population, and changed little during the study period. A detailed quantification of the independent effect of duration of mother's diabetes on birthweight revealed a continuous inverse correlation between these two variables.

The Diabetes and Pre-eclampsia Intervention Trial.

OBJECTIVE: Rates of pre-eclampsia in women with type 1 diabetes are two to four times higher than in normal pregnancies. Diabetes is associated with antioxidant depletion and increased free radical production, and an increasing body of evidence suggests that oxidative stress and endothelial cell activation may be relevant to disease pathogenesis in pre-eclampsia. The Diabetes and Pre-eclampsia Intervention Trial (DAPIT) aims to establish if pregnant women with type 1 diabetes supplemented with vitamins C and E have lower rates of pre-eclampsia and endothelial activation compared with placebo treatment. METHODS: DAPIT is a randomised multicentre double-blind placebo-controlled trial that will recruit 756 pregnant women with type 1 diabetes from 20 metabolic-antenatal clinics in the UK over 4 years. Women are randomised to daily vitamin C (1000 mg) and vitamin E (400 IU) or placebo at 8-22 weeks of gestation until delivery. Maternal venous blood is obtained at randomisation, 26 and 34 weeks, for markers of endothelial activation and oxidative stress and to assess glycaemic control. The primary outcome of DAPIT is pre-eclampsia. Secondary outcomes include endothelial activation (PAI-1/PAI-2) and birthweight centile.

The relationship between birth weight and maternal glycated haemoglobin (HbA1c) concentration in pregnancies complicated by Type 1 diabetes.

AIM: To examine the relationships between maternal HbA1c concentration at different time points and birth weight in pregnancies complicated by pre-existing Type 1 diabetes. METHODS: A comprehensive audit dataset was collected prospectively on all deliveries in Scotland to women with pre-existing Type 1 diabetes occurring between 1 April 1998 and 31 March 1999. Data items included HbA1c concentrations prior to conception and in each of the three trimesters of pregnancy, and birth weight. Relationships between standardized birth weight and HbA1c concentrations at each of the four time points were examined using correlation analysis. RESULTS: Standardized birth weight (Z scores) could be calculated for 203 of 208 singleton liveborn infants. HbA1c concentrations, standardized to correct for assay differences among hospitals, at different time points were available for between 134 (pre-pregnancy) and 192 (third trimester) cases. Standardized birth weight, relative to a reference population, showed a unimodal distribution, shifted to the right (mean, +1.57 sd). There was a significant negative correlation between pre-pregnancy HbA1c and birth weight (Spearman's R, -0.208; P = 0.016). There were no statistically significant correlations for other time points. CONCLUSIONS: Standardized birth weight scores of the infants of diabetic mothers are higher than those of a reference population. There is no simple relationship between maternal glycaemic status and birth weight, but there appears to be a paradoxical inverse relationship between pre-pregnancy glycaemic control and standardized birth weight.