Socio-economic differences in cardiovascular disease risk factor prevalence in people with type 2 diabetes in Scotland: a cross-sectional study.

AIM: To describe the association between socio-economic status and prevalence of key cardiovascular risk factors in people with type 2 diabetes in Scotland. METHODS: A cross-sectional study of 264 011 people with type 2 diabetes in Scotland in 2016 identified from the population-based diabetes register. Socio-economic status was defined using quintiles of the area-based Scottish Index of Multiple Deprivation (SIMD) with quintile (Q)1 and Q5 used to identify the most- and least-deprived fifths of the population, respectively. Logistic regression models adjusted for age, sex, health board, history of cardiovascular disease and duration of diabetes were used to estimate odds ratios (ORs) for Q1 compared with Q5 for each risk factor. RESULTS: The mean (sd) age of the study population was 66.7 (12.8) years, 56% were men, 24% were in Q1 and 15% were in Q5. Crude prevalence in Q1/Q5 was 24%/8.8% for smoking, 62%/49% for BMI ≥ 30 kg/m2 , 44%/40% for HbA1c ≥ 58 mmol/mol (7.5%), 31%/31% for systolic blood pressure (SBP) ≥ 140 mmHg, and 24%/25% for total cholesterol ≥ 5 mmol/l, respectively. ORs [95% confidence intervals (CI)] were 3.08 (2.95-3.21) for current smoking, 1.48 (1.44-1.52) for BMI ≥ 30 kg/m2 , 1.11 (1.08-1.15) for HbA1c ≥ 58 mmol/mol (7.5%), 1.03 (1.00-1.06) for SBP ≥ 140 mmHg and 0.87 (0.84-0.90) for total cholesterol ≥ 5 mmol/l. CONCLUSIONS: Socio-economic deprivation is associated with higher prevalence of smoking, BMI ≥ 30 kg/m2 and HbA1c ≥ 58 mmol/mol (7.5%), and lower prevalence of total cholesterol ≥ 5 mmol/l among people with type 2 diabetes in Scotland. Effective approaches to reducing inequalities are required as well as reducing risk factor prevalence across the whole population.

Socio-economic status and mortality in people with type 1 diabetes in Scotland 2006-2015: a retrospective cohort study.

AIMS: To describe the association between socio-economic status and mortality in a nation-wide cohort of people with type 1 diabetes in Scotland and to compare patterns over time and with the general population. METHODS: A retrospective cohort study was performed using data for people with type 1 diabetes from a population-based register linked to mortality records. Socio-economic status was derived from quintiles of an area-based measure: the Scottish Index of Multiple Deprivation. Sex-specific directly age-standardized mortality rates for each Scottish Index of Multiple Deprivation quintile and rate ratios comparing the most vs least deprived quintile were calculated for two time periods: 2006-2010 and 2011-2015. Data for the population without type 1 diabetes between 2011 and 2015 were available for comparison. RESULTS: Data for 3802 deaths among 33 547 people with type 1 diabetes were available. The age-standardized mortality rate per 1000 person-years decreased over time (from 2006-2010 to 2011-2015) for men and women with type 1 diabetes: 24.8 to 20.2 and 22.5 to 17.6, respectively. Mortality in populations with and without type 1 diabetes was generally higher for men than women and was inversely associated with socio-economic status. Rate ratios for the most vs least deprived groups increased over time among people with type 1 diabetes (men: 2.49 to 2.81; women: 1.92 to 2.86) and were higher than among populations without type 1 diabetes in 2011-2015 (men: 2.06; women: 1.66). CONCLUSIONS: Socio-economic deprivation was associated with a steeper mortality gradient in people with type 1 diabetes than in the population without type 1 diabetes in Scotland. Age-standardized mortality has decreased over time but socio-economic inequalities may be increasing.

The cost of prevalent and incident cardiovascular disease in people with type 2 diabetes in Scotland: data from the Scottish Care Information-Diabetes Collaboration.

AIM: To compare costs for three groups of people with type 2 diabetes, those at high risk of future cardiovascular disease, those without cardiovascular disease and those with established cardiovascular disease, and to also compare costs incurred by people with type 2 diabetes with an incident cardiovascular disease event with those who remain incident event-free over a 3-year period. METHODS: Data about people with type 2 diabetes in Scotland were obtained from the Scottish Care Information Diabetes registry. Data linkage was used to retrieve information on healthcare utilization, care home use and deaths. Productivity effects were estimated for those of non-pensionable age. We estimated costs over 12 months (prevalent cardiovascular disease) and 3 years from incident cardiovascular disease event. RESULTS: Mean annual cost per person with established cardiovascular disease was £6900, £3300 for a person at high risk of future cardiovascular disease, and £2500 for a person without cardiovascular disease and not at high risk. In year 1, the cost of an incident cardiovascular disease event was £16 700 compared with £2100 for people without an incident event. Over 2 years, the cumulative costs were £21 500 and £4200, and by year 3, £25 000 and £5900, respectively. CONCLUSIONS: Cardiovascular disease in people with type 2 diabetes places a significant financial burden on healthcare and the wider economy. Our results emphasize the financial consequences of cardiovascular disease prevention strategies.

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese.

BACKGROUND AND AIMS: It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese. METHODS AND RESULTS: As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women. CONCLUSIONS: In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.

Ferritin levels throughout childhood and metabolic syndrome in adolescent stage.

BACKGROUND AND AIM: Increased ferritin levels have been widely associated with cardiovascular risk in adults. Whether ferritin levels and their changes during childhood are related to metabolic syndrome (MetS) at adolescence is unknown. We aimed to evaluate these associations using levels of ferritin at 5, 10 and 16 years and their linear increases and patterns of sustained increased levels across childhood. METHODS AND RESULTS: There were four samples evaluated according to non-missing values for study variables at each stage (5 years: 562; 10 years: 381; and 16 years: 567 children; non-missing values at any stage: 379). MetS risk was evaluated as a continuous Z score. Patterns of sustained increased ferritin (highest tertile) and slope of the change of ferritin per year across the follow-up were calculated. Ferritin levels in the highest versus lowest tertile at five and 16 years were significantly positively associated with MetS risk Z score at adolescence in boys and these associations were unaffected by adjustment for covariates. Having high, compared to low/moderate ferritin level at 2 or more time periods between 5 and 16 years was related to higher Mets Z-score in boys only [e.g. 5-10 years adjusted-beta (95 %CI):0.26 (0.05-0.48),P < 0.05]. In girls, ferritin Z score at 10 and 16 years was positively and independently associated with HOMA-IR Z score. In girls, the slope of ferritin per year in the highest tertile was positively associated with MetS risk Z-score [adjusted-beta (95 %CI):0.21 (0.05-0.38),P < 0.05]. CONCLUSIONS: Ferritin levels throughout childhood are positively related to cardiometabolic risk in adolescence, with associations varying by sex.

Incident ischaemic stroke and Type 2 diabetes: trends in incidence and case fatality in Scotland 2004-2013.

AIM: To describe trends in first ischaemic stroke incidence and case fatality in adults with and without a diagnosis of Type 2 diabetes prior to their ischaemic stroke event in Scotland between 2004 and 2013. METHODS: Using population-wide hospital admission, death and diabetes datasets, we conducted a retrospective cohort study. Negative binomial and logistic regression models were used to calculate year-specific incidence and case-fatality rates for people with Type 2 diabetes and for people without diabetes. RESULTS: During 41.0 million person-years of follow-up there were 69 757 ischaemic stroke events. Type 2 diabetes prevalence among patients who experienced ischaemic stroke increased from 13.5% to 20.3% between 2004 and 2013. Stroke incidence rates declined by 2.7% (95% CI 2.4, 3.0) annually for people with and without diabetes [diabetes/year interaction: rate ratio 0.99 (95% CI 0.98, 1.01)]. Type 2 diabetes was associated with an increased risk of ischaemic stroke in men [rate ratio 1.23 (95% CI 1.17, 1.30)] and women [rate ratio 1.41 (95% CI 1.35, 1.48)]. Case-fatality rates were 14.2% and 12.7% in people with Type 2 diabetes and without diabetes, respectively. Case fatality declined by 3.5% (95% CI 2.7, 4.5) annually [diabetes/year interaction: odds ratio 1.01 (95% CI 0.98, 1.02)]. CONCLUSIONS: Ischaemic stroke incidence declined no faster in people with a diagnosis of Type 2 diabetes than in people without diabetes. Increasing prevalence of Type 2 diabetes among stroke patients may mean that declines in case fatality over time will be less marked in the future.

Associations between weight change and biomarkers of cardiometabolic risk in South Asians: secondary analyses of the PODOSA trial.

BACKGROUND/OBJECTIVES: The association of weight changes with cardiometabolic biomarkers in South Asians has been sparsely studied. SUBJECTS/METHODS: We measured cardiometabolic biomarkers at baseline and after 3 years in the Prevention of Diabetes and Obesity in South Asians Trial. We investigated the effect of a lifestyle intervention on biomarkers in the randomized groups. In addition, treating the population as a single cohort, we estimated the association between change in weight and change in biomarkers. RESULTS: Complete data were available at baseline and after 3 years in 151 participants. At 3 years, there was an adjusted mean reduction of 1·44 kg (95% confidence interval (95% CI): 0.18-2.71) in weight and 1.59 cm (95% CI: 0.08-3.09) in waist circumference in the intervention arm as compared with the control arm. There was no clear evidence of difference between the intervention and control arms in change of mean value of any biomarker. As a single cohort, every 1 kg weight reduction during follow-up was associated with a reduction in triglycerides (-1.3%, P=0.048), alanine aminotransferase (-2.5%, P=0.032), gamma-glutamyl transferase (-2.2%, P=0.040), leptin (-6.5%, P<0.0001), insulin (-3.7%, P=0.0005), fasting glucose (-0.8%, P=0.0071), 2-h glucose (-2.3%, P=0.0002) and Homeostatic Model Assessment of insulin resistance (HOMA-IR: -4.5%, P=0.0002). There was no evidence of associations with other lipid measures, tissue plasminogen activator, markers of inflammation or blood pressure. CONCLUSIONS: We demonstrate that modest weight decrease in SAs is associated with improvements in markers of total and ectopic fat as well as insulin resistance and glycaemia in South Asians at risk of diabetes. Future trials with more intensive weight change are needed to extend these findings.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

AIMS: Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries. METHODS: Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex. RESULTS: Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available. CONCLUSION: These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

Comparing ischaemic stroke in six European countries. The EuroHOPE register study.

BACKGROUND AND PURPOSE: The incidence of hospitalizations, treatment and case fatality of ischaemic stroke were assessed utilizing a comprehensive multinational database to attempt to compare the healthcare systems in six European countries, aiming also to identify the limitations and make suggestions for future improvements in the between-country comparisons. METHODS: National registers of hospital discharges for ischaemic stroke identified by International Classification of Diseases codes 433-434 (ICD-9) and code I63 (ICD-10), medication purchases and mortality were linked at the patient level in each of the participating countries and regions: Finland, Hungary, Italy, the Netherlands, Scotland and Sweden. Patients with an index admission in 2007 were followed for 1 year. RESULTS: In all, 64,170 patients with a disease code for ischaemic stroke were identified. The number of patients registered per 100,000 European standard population ranged from 77 in Scotland to 407 in Hungary. Large differences were observed in medication use. The age- and sex-adjusted all-cause case fatality amongst hospitalized patients at 1 year from stroke was highest in Hungary at 31.0% (95% confidence interval 30.5-31.5). Regional differences in age- and sex-adjusted 1-year case fatality within countries were largest in Hungary (range 23.6%-37.6%) and smallest in the Netherlands (20.5%-27.3%). CONCLUSIONS: It is feasible to link population-wide register data amongst European countries to describe incidence of hospitalizations, treatment patterns and case fatality of ischaemic stroke on a national level. However, the coverage and validity of administrative register data for ischaemic stroke should be developed further, and population-based and clinical stroke registers should be created to allow better control of case mix.

Subsequent hospitalisation experience of 5-year survivors of childhood, adolescent, and young adult cancer in Scotland: a population based, retrospective cohort study.

BACKGROUND: Survivors of childhood, adolescent, and young adult cancer are known to be at risk of late effects of their disease and its treatment. Most population-based studies of cancer survivors have reported on second primary cancers and mortality. The aim of this study was to research acute and psychiatric hospital admission rates and length of stay in 5-year survivors of cancer diagnosed before the age of 25 years. METHODS: This was a population-based retrospective cohort study using linked national cancer registry, acute hospital discharge, psychiatric hospital, and mortality records. The study population consisted of 5229 individuals who were diagnosed with cancer before the age of 25 years between 1981 and 2003, and who survived at least 5 years after the date of diagnosis of their primary cancer. Indirect standardisation for age and sex was used to calculate standardised bed days and hospitalisation ratios (SBDR and SHR) for both acute and psychiatric hospital admissions, and absolute excess risks (AERs) compared with the general Scottish population. RESULTS: Five-year survivors of cancer, diagnosed before the age of 25 years, are at increased risk of admission to acute hospitals (SHR 2.8; 95% confidence interval 2.7-2.9) and of spending more time in hospital (SBDR 3.7; 3.6-3.7). Corresponding AERs were 6.4 (6.0-6.6) admissions and 64.8 (64.4-66.9) bed days per 100 cancer survivors per year. In contrast, 5-year survivors were not at higher risk of admission to psychiatric hospital (SHR 0.9; 0.8-1.2), and they spent significantly less time as psychiatric in-patients (SBDR 0.4; 0.4-0.4) compared with the whole population. CONCLUSION: Using routinely collected linked records, our population-based study has demonstrated increased rates of hospitalisation in 5-year survivors of cancer diagnosed before the age of 25 years. Long-term clinical follow-up of survivors of cancer in this age group should focus on the prevention and treatment of the late effects of cancer in those patients at highest risk of hospitalisation.

Factors associated with statin treatment for the primary prevention of cardiovascular disease in people within 2 years following diagnosis of diabetes in Scotland, 2006-2008.

AIM: To describe characteristics associated with statin prescribing for the primary prevention of cardiovascular disease in people with newly diagnosed diabetes. METHODS: Data from the Scottish Care Information-Diabetes Collaboration data set for 2006-2008 were used. This data set contains socio-demographic and prescribing data for over 99% of people with diagnosed diabetes in Scotland. Analyses were conducted on people aged over 40 years diagnosed with Type 1 or Type 2 diabetes between 2006 and 2008 with complete data and no previous history of cardiovascular or statin prescription. Logistic regression was used to calculate odds ratios for statin prescription in the 2 years following diagnosis of diabetes. RESULTS: There were 7157 men and 5601 women who met the inclusion criteria, 68% of whom had a statin prescription recorded in the 2 years following diagnosis of diabetes. The proportions receiving statins were lower above 65 years of age in men and 75 years of age in women. People with Type 1 diabetes had lower odds of receiving statins than people with Type 2 diabetes [odds ratio (95% CI) 0.42 (0.29-0.61) for men and 0.48 (0.28-0.81) for women, after adjustment for age, BMI, smoking status, cholesterol level and deprivation]. Higher total cholesterol, BMI and being a current smoker were associated with greater odds of statin prescription. CONCLUSION: Approximately one third of the study population had no record of statin prescription during the 2 years after diagnosis of diabetes. Cardiovascular disease risk reduction opportunities may be missed in some of these people.

Deprivation and access to treatment for colorectal cancer in Southeast Scotland 2003-2009.

AIM: Socioeconomic deprivation is associated with poorer survival from colorectal cancer. We examined the association of deprivation with access to treatment, disease stage at presentation and choice of treatment for colorectal cancer within a regional managed clinical network. METHOD: We performed a retrospective analysis of data from the Southeast Scotland Cancer Network colorectal database for the period 2003-2009. Socioeconomic status was assigned into five categories using postcode of residence and the Scottish Index of Multiple Deprivation score. Outcomes were access to consultation and treatment, stage of disease at presentation and treatment factors (type of surgery, adjuvant radiotherapy and adjuvant chemotherapy). RESULTS: Of 4960 colorectal cancer patients, 4016 patients (81%) underwent operative treatment. Deprivation was not associated with age, gender, tumour site, disease stage, delay in treatment pathway or permanent stoma rate. Primary tumour resection (P = 0.006) and chemotherapy treatment (P = 0.018) were higher in the least deprived compared with the most deprived quintile. Socioeconomic status was associated with both primary tumour resection [odds ratio for the most affluent compared with the most deprived quintiles (OR) 1.34, 95% confidence interval (CI) 1.05-1.72, P = 0.018] and chemotherapy treatment (OR 1.44, 95% CI 1.15-1.80, P = 0.001). However, when health board of treatment was added to the model, only chemotherapy treatment was independently associated with deprivation (OR 1.46, 95% CI 1.16-1.83, P = 0.001). CONCLUSION: Deprivation is not associated with treatment delay or more advanced disease stage at presentation. An apparent association between deprivation and treatment choice may be explained by other differences between patients treated in different areas.

Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes (2000-2007).

AIMS/HYPOTHESIS: The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on (1) survival (overall and cause-specific) in multiple time intervals after diagnosis of colorectal cancer and (2) cause of death. METHODS: Data from the Scottish Cancer Registry were linked to data from a population-based national diabetes register. All people in Scotland diagnosed with non-metastatic cancer of the colon or rectum in 2000-2007 were included. The effect of pre-existing type 2 diabetes on survival over four discrete time intervals (<1, 1-2, 3-5 and >5 years) after cancer diagnosis was assessed by Cox regression. Cumulative incidence functions were calculated representing the respective probabilities of death from the competing causes of colorectal cancer, cardiovascular disease, other cancers and any other cause. RESULTS: Data were available for 19,505 people with colon or rectal cancer (1,957 with pre-existing diabetes). Cause-specific mortality analyses identified a stronger association between diabetes and cardiovascular disease mortality than that between diabetes and cancer mortality. Beyond 5 years after colon cancer diagnosis, diabetes was associated with a detrimental effect on all-cause mortality after adjustment for age, socioeconomic status and cancer stage (HR [95% CI]: 1.57 [1.19, 2.06] in men; 1.84 [1.36, 2.50] in women). For patients with rectal cancer, diabetes was not associated with differential survival in any time interval. CONCLUSIONS/INTERPRETATION: Poorer survival observed for colon cancer associated with type 2 diabetes in Scotland may be explained by higher mortality from causes other than cancer.

Type 2 diabetes, socioeconomic status and risk of cancer in Scotland 2001-2007.

AIMS/HYPOTHESIS: The objective of this study was to use Scottish national data to assess the influence of type 2 diabetes on the risk of cancer at 16 different sites, while specifically investigating the role of confounding by socioeconomic status in the diabetes-cancer relationship. METHODS: All people in Scotland aged 55-79 years diagnosed with any of the cancers of interest during the period 2001-2007 were identified and classified by the presence/absence of co-morbid type 2 diabetes. The influence of diabetes on cancer risk for each site was assessed via Poisson regression, initially with adjustment for age only, then adjusted for both age and socioeconomic status. RESULTS: There were 4,285 incident cancers in people with type 2 diabetes. RR for any cancers (adjusted for age only) was 1.11 (95% CI 1.05, 1.17) for men and 1.33 (1.28, 1.40) for women. Corresponding values after additional adjustment for socioeconomic status were 1.10 (1.04, 1.15) and 1.31 (1.25, 1.38), respectively. RRs for individual cancer sites varied markedly. CONCLUSIONS/INTERPRETATION: Socioeconomic status was found to have little influence on the association between type 2 diabetes and cancer.

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.

External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants?

AIMS: To describe the proportion of people with Type 2 diabetes living in Scotland who meet eligibility criteria for inclusion in several large randomized controlled trials of glycaemic control to inform physicians and guideline developers about the generalizibility of trial results. METHODS: A literature review was performed to identify large trials assessing the impact of glycaemic control on risk of macrovascular disease. Inclusion and exclusion criteria from each trial were applied to data on the population of people with a diagnosis of Type 2 diabetes living in Scotland in 2008 (n = 180,590) in a population-based cross-sectional study and the number and proportion of people eligible for each trial was determined. RESULTS: Seven trials were identified. The proportion of people with Type 2 diabetes who met the eligibility criteria for the trials ranged from 3.5 to 50.7%. Trial participants were younger at age of diagnosis of diabetes and at time of trial recruitment than in the Scottish study population. The application of upper age criteria excluded the largest proportion of patients, with up to 39% of people with Type 2 diabetes ineligible for a trial with the most stringent criteria based on age alone. CONCLUSIONS: We found that many of the large trials of glycaemic control among people with Type 2 diabetes have limited external validity when applied to a population-based cohort of people with Type 2 diabetes. In particular, the age distribution of trial participants often does not reflect that of people with Type 2 diabetes in a contemporary British population.

Lipoprotein (a), metabolic syndrome and coronary calcium score in a large occupational cohort.

BACKGROUND AND AIMS: Whether lipoprotein (a) [Lp(a)] concentration is associated with metabolic syndrome (MetS) and pre-clinical atherosclerosis in different ethnic groups is uncertain. The association between Lp(a), MetS and a measure of pre-clinical atherosclerosis was studied in a large Asian cohort. METHODS AND RESULTS: Data were analyzed from a South Korean occupational cohort who underwent a cardiac computed tomography (CT) estimation of CAC score and measurements of cardiovascular risk factors (n = 14,583 people). The key exposure was an Lp(a) concentration in the top quartile (>38.64 mg/dL)) with a CAC score >0 as the outcome variable and measure of pre-clinical atherosclerosis. Logistic regression was used to describe the associations. 1462 participants had a CAC score >0. In the lowest Lp(a) quartile (<11.29 mg/dL), 25.8% had MetS, compared with 16.1% in the highest Lp(a) quartile (>38.64 mg/dL (p < 0.001). MetS, and component features, were inversely related to Lp(a) concentration (all p < 0.0001). In the highest Lp(a) quartile group, there was an association between Lp(a) and CAC score >0 in men (OR 1.21[1.05, 1.40], p = 0.008), and women (OR 1.62[1.03, 2.55], p = 0.038), after adjustment for age, sex, lipid lowering therapy, and multiple cardiovascular risk factors. There was no evidence of an interaction between highest quartile Lp(a) and either high LDLc (>147 mg/dL) (p = 0.99), or MetS (p = 0.84) on the association with CAC score >0. CONCLUSION: Lp(a) levels are inversely related to MetS and its components. There was a robust association between Lp(a) concentration >38.6 mg/dL and marker of early atherosclerosis in both men and women, regardless of LDLc, level MetS or other cardiovascular risk factors.

Diabetes and cancer (2): evaluating the impact of diabetes on mortality in patients with cancer.

In this paper we address methodological aspects of aetiological importance in the link between diabetes and mortality in patients with cancer. We identified nine key points on the cancer pathway at which confounding may arise-cancer screening use, stage at diagnosis, cancer treatment selection, cancer treatment complications and failures, peri-treatment mortality, competing risks for long-term mortality, effects of type 2 diabetes on anti-cancer therapies, effects of glucose-lowering treatments on cancer outcome and differences in tumour biology. Two types of mortality studies were identified: (1) inception cohort studies that evaluate the effect of baseline diabetes on cancer-related mortality in general populations, and (2) cohorts of patients with a cancer diagnosis and pre-existing type 2 diabetes. We demonstrate, with multiple examples from the literature, that pre-existing diabetes affects presentation, cancer treatment, and outcome of several common cancer types, often to varying extents. Diabetes is associated with increased all-cause mortality in cancer patients, but the evidence that it influences cancer-specific mortality is inconsistent. In the absence of data that address the potential biases and confounders outlined in the above framework, we caution against the reporting of cancer-related mortality as a main endpoint in analyses determining the impact of diabetes and glucose-lowering medications on risk of cancer.

Area-based socioeconomic status, type 2 diabetes and cardiovascular mortality in Scotland.

AIMS/HYPOTHESIS: The aim of this study was to explore the relationships between type 2 diabetes mellitus, area-based socioeconomic status (SES) and cardiovascular disease mortality in Scotland. METHODS: We used an area-based measure of SES, Scottish national diabetes register data linked to mortality records, and general population cause-specific mortality data to investigate the relationships between SES, type 2 diabetes and mortality from ischaemic heart disease (IHD) and cerebrovascular disease (CbVD), for 2001-2007. We used negative binomial regression to obtain age-adjusted RRs of mortality (by sex), comparing people with type 2 diabetes with the non-diabetic population. RESULTS: Among 216,652 people aged 40 years or older with type 2 diabetes (980,687 person-years), there were 10,554 IHD deaths and 4,378 CbVD deaths. Age-standardised mortality increased with increasing deprivation, and was higher among men. IHD mortality RRs were highest among the least deprived quintile and lowest in the most deprived quintile (men: least deprived, RR 1.94 [95% CI 1.61, 2.33]; most deprived, RR 1.46 [95% CI 1.23, 1.74]) and were higher in women than men (women: least deprived, RR 2.84 [95% CI 2.12, 3.80]; most deprived, RR 2.04 [95% CI 1.55, 2.69]). A similar, weaker, pattern was observed for cerebrovascular mortality. CONCLUSIONS/INTERPRETATION: Absolute risk of cardiovascular mortality is higher in people with diabetes than in the non-diabetic population and increases with increasing deprivation. The relative impact of diabetes on cardiovascular mortality differs by SES, and further efforts to reduce cardiovascular risk both in deprived groups and people with diabetes are required. Prevention of diabetes may reduce socioeconomic health inequalities.