Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes.

Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans = 302, South Asians = 161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from the MoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.

Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans.

CONTEXT: Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown. OBJECTIVE: This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity. METHODS: We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization. RESULTS: In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (ß [95% CI] -0.19 [-0.21 to -0.17]), body fat (-0.12 [-0.14 to -0.10), and fasting C-peptide (-2.04 [-2.46 to -1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58], and -0.20 [-0.36 to -0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R. CONCLUSION: BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling.

The total prevalence of diagnosed diabetes and the quality of diabetes care for the adult population in Salten, Norway.

Objective: To assess the total prevalence of types 1 and 2 diabetes and to describe and compare cardiovascular risk factors, vascular complications and the quality of diabetes care in adults with types 1 and 2 diabetes in Salten, Norway. Research design and methods: Cross-sectional study including all patients with diagnosed diabetes in primary and specialist care in Salten, 2014 (population 80,338). Differences in cardiovascular risk factors, prevalence of vascular complications and attained treatment targets between diabetes types were assessed using regression analyses. Results: We identified 3091 cases of diabetes, giving a total prevalence in all age groups of 3.8%, 3.4% and 0.45% for types 2 and 1 diabetes, respectively. In the age group 30-89 years the prevalence of type 2 diabetes was 5.3%. Among 3027 adults aged 18 years and older with diabetes, 2713 (89.6%) had type 2 and 304 (10.0%) type 1 diabetes. The treatment target for haemoglobin A1c (⩽7.0%/53 mmol/mol) was reached in 61.1% and 22.5% of types 2 and 1 diabetes patients, respectively. After adjusting for age, sex and diabetes duration we found differences between patients with types 2 and 1 diabetes in mean haemoglobin A1c (7.1% vs. 7.5%, P<0.001), blood pressure (136/78 mmHg vs. 131/74 mmHg, P<0.001) and prevalence of coronary heart disease (23.1% vs. 15.8%, P<0.001). Conclusions: The prevalence of diagnosed type 2 diabetes was slightly lower than anticipated. Glycaemic control was not satisfactory in the majority of patients with type 1 diabetes. Coronary heart disease was more prevalent in patients with type 2 diabetes.

High adherence to recommended diabetes follow-up procedures by general practitioners is associated with lower estimated cardiovascular risk.

AIMS: To explore whether the general practitioners' (GPs') performance of recommended processes of care was associated with estimated risk of cardiovascular disease (CVD) and poor glycaemic control in patients with type 2 diabetes. METHODS: A cross-sectional study from Norwegian general practice including 6015 people with type 2 diabetes <75 years old, without CVD and their 275 GPs. The GPs were split into quintiles based on each GP's average performance of six recommended processes of care. The quintiles were the exposure variable in multilevel regression models with 10-year risk of cardiovascular events estimated by NORRISK 2 (total and modifiable fraction) and poor glycaemic control (HbA1c >69 mmol/mol (>8.5%)) as outcome variables. RESULTS: The mean total and modifiable estimated 10-year CVD risk was 12.3% and 3.3%, respectively. Compared with patients of GPs in the highest-performing quintile, patients treated by GPs in the lowest quintile had an adjusted total and modifiable CVD risk that was 1.88 (95% CI 1.17-2.60) and 1.78 (1.14-2.41) percent point higher. This represents a relative mean difference of 16.6% higher total and 74.8% higher modifiable risk among patients of GPs in the lowest compared with the highest quintile. For patients with GPs in the lowest-performing quintile, the adjusted odds of poor glycaemic control was 1.77 (1.27-2.46) times higher than that for patients with a GP in the highest quintile. CONCLUSIONS: We found a pattern of lower CVD risk and better glycaemic control in patients of GPs performing more recommended diabetes processes of care.

Factors associated with treatment in primary versus specialist care: A population-based study of people with type 2 and type 1 diabetes.

AIMS: The objectives of this study are to identify the proportion and characteristics of people with type 1 and 2 diabetes treated in primary, specialist and shared care and to identify the proportion of persons with type 2 diabetes reaching HbA1c treatment targets and the clinical risk factors and general practitioner and practice characteristics associated with treatment in specialist care. METHODS: Population-based cross-sectional study including all adults ≥18 years diagnosed with diabetes in primary and specialist care in Salten, Norway. We used multivariable mixed-effects logistic regression models with level of care as outcome variable and population, general practitioner, and practice characteristics as exposure variables. RESULTS: Of 2704 people with type 2 diabetes, 13.5% were treated in shared care and 2.1% in specialist care only. Of 305 people with type 1 diabetes, 14.4% received treatment in primary care only. The HbA1c treatment target of 53 mmol/mol (7.0%) was reached by 67.3% of people with type 2 diabetes in primary care versus 30.4% in specialist care. HbA1c , use of insulin, coronary heart disease, retinopathy and urban practice location were positively associated with treatment in specialist care. General practitioners' use of a structured form and a diabetes nurse were negatively associated with specialist care. CONCLUSIONS: Of people with type 2 diabetes, 16% were treated in specialist care. They had higher HbA1c and more vascular complications, as expected from priority guidelines. The use of a structured diabetes form and diabetes nurses seem to support type 2 diabetes follow-up in primary care.

Factors associated with potential over- and undertreatment of hyperglycaemia and annual measurement of HbA1c in type 2 diabetes in norwegian general practice.

AIMS: To identify individual and general practitioner (GP) characteristics associated with potential over- and undertreatment of hyperglycaemia in type 2 diabetes and with HbA1c not being measured. METHODS: A cross-sectional study that included 10233 individuals with type 2 diabetes attending 282 GPs. Individuals with an HbA1c measurement during the last 15 months were categorized as potentially overtreated if they were prescribed a sulphonylurea and/or insulin when the HbA1c was less than 53 mmol/mol (7%) when aged over 75 years or less than 48 mmol/mol (6.5%) when aged between 65 and 75 years. Potential undertreatment was defined as age less than 60 years and HbA1c > 64 mmol/mol (8.0%) or HbA1c > 69 mmol/mol (8.5%) and treated with lifestyle modification and/or monotherapy. We used multilevel binary and multinominal logistic regression models to examine associations. RESULTS: Overall, 4.1% were potentially overtreated, 7.8% were potentially undertreated and 11% did not have HbA1c measured. Characteristics associated with potential overtreatment were as follows: long diabetes duration, prescribed antihypertensive medication, cardiovascular disease and renal failure. Potential undertreatment was associated with male gender, non-western origin and low educational level. Characteristics associated with not having an HbA1c measurement performed were male gender, age < 50 years and cardiovascular diseases. GP specialist status and GPs' use of a Noklus diabetes application reduced the risk of not having an HbA1c measurement performed. CONCLUSION: Potential overtreatment in elderly individuals with type 2 diabetes was relatively low. Nevertheless, appropriate de-intensification or intensification of treatment and regular HbA1c measurement in identified subgroups is warranted.

Variation between general practitioners in type 2 diabetes processes of care.

AIMS: To explore variation in general practitioners' (GPs') performance of six recommended procedures in type 2 diabetes patients <75 years without cardiovascular disease. METHODS: Cross-sectional study of quality of diabetes care in Norway based on electronic health records from 2014. GPs (clustered in practices) were divided in quintiles based on a composite measure of performance of six processes of care. We fitted a multilevel partial ordinal regression model to identify GP factors associated with being in quintiles with better performance. RESULTS: We identified 6015 type 2 diabetes patients from 275 GPs in 77 practices. The GPs performed on average 63.4% of the procedures; on average 46% in the poorest quintile to 81% in the best quintile with a larger range in individual GPs. After adjustments, use of a structured follow-up form was associated with GPs being in upper three quintiles (OR 12.4 (95% CI 2.37-65.1). Routines for reminders were associated with being in a better quintile (OR 2.6 (1.37-4.92). GPs' age >60 years and heavier workload were associated with poorer performance. CONCLUSION: We found large variations in GPs' performance of processes of care. Factors reflecting structure and workload were strongly associated with performance.

Gestational diabetes mellitus by maternal country of birth and length of residence in immigrant women in Norway.

AIMS: Immigrant women are at higher risk for gestational diabetes mellitus (GDM) than non-immigrant women. This study described the prevalence of GDM in immigrant women by maternal country of birth and examined the associations between immigrants' length of residence in Norway and GDM. METHODS: This Norwegian national population-based study included 192,892 pregnancies to immigrant and 1,116,954 pregnancies to non-immigrant women giving birth during the period 1990-2013. Associations were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression models, adjusted for year of delivery, maternal age, marital status, health region, parity, education and income. RESULTS: The prevalence and adjusted OR [CI] for GDM were substantially higher in immigrant women from Bangladesh (7.4%, OR 8.38 [5.41, 12.97]), Sri Lanka (6.3%, OR 7.60 [6.71, 8.60]), Pakistan (4.3%, OR 5.47 [4.90, 6.11]), India (4.4%, OR 5.18 [4.30, 6.24]) and Morocco (4.3%, OR 4.35 [3.63, 5.20]) compared to non-immigrants (prevalence 0.8%). Overall, GDM prevalence increased from 1.3% (OR 1.25 [1.14, 1.36]) to 3.3% (OR 2.55 [2.39, 2.71]) after 9 years of residence in immigrants compared to non-immigrant women. This association was particularly strong for women from South Asia. CONCLUSIONS: Gestational diabetes mellitus prevalence varied substantially between countries of maternal birth and was particularly high in immigrants from Asian countries. GDM appeared to increase with longer length of residence in certain immigrant groups.

Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians.

Background: Leptin, mainly secreted by fat cells, plays a core role in the regulation of appetite and body weight, and has been proposed as a mediator of metabolic programming. During pregnancy leptin is also secreted by the placenta, as well as being a key regulatory cytokine for the development, homeostatic regulation and nutrient transport within the placenta. South Asians have a high burden of type 2 diabetes, partly attributed to a "thin-fat-phenotype". Objective: Our aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene (LEP) DNA methylation. Methods: We performed DNA methylation analyses of 13 placental LEP CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort. Results: South Asian ethnicity and gestational diabetes (GDM) were associated with higher placental LEP methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p<0.001], and the strongest associations with GDM was seen for CpG5 [5.2% (1.4, 9.0), p=0.008]. Higher maternal LDL-cholesterol was associated with lower placental LEP methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p<0.001]. After adjustments, including for nutritional factors involved in the one-carbon-metabolism cycle (vitamin D, B12 and folate levels), ethnic differences in placental LEP methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted. Conclusions: Maternal glucose and lipid metabolism is related to placental LEP methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. OBJECTIVES: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. DESIGN: This was an individual participant data meta-analysis of cohort studies. SETTING: Source data from secondary and tertiary care. PREDICTORS: We identified predictors from systematic reviews, and prioritised for importance in an international survey. PRIMARY OUTCOMES: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia. ANALYSIS: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. RESULTS: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. LIMITATIONS: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. FUTURE WORK: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015029349. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Pre-eclampsia, a condition in pregnancy that results in raised blood pressure and protein in the urine, is a major cause of complications for the mother and baby. WHAT IS NEEDED?: A way of accurately identifying women at high risk of pre-eclampsia to allow clinicians to start preventative interventions such as administering aspirin or frequently monitoring women during pregnancy. WHERE ARE THE RESEARCH GAPS?: Although over 100 tools (models) have been reported worldwide to predict pre-eclampsia, to date their performance in women managed in the UK NHS is unknown. WHAT DID WE PLAN TO DO?: We planned to comprehensively identify all published models that predict the risk of pre-eclampsia occurring at any time during pregnancy and to assess if this prediction is accurate in the UK population. If the existing models did not perform satisfactorily, we aimed to develop new prediction models. WHAT DID WE FIND?: We formed the International Prediction of Pregnancy Complications network, which provided data from a large number of studies (78 studies, 25 countries, 125 researchers, 3,570,993 singleton pregnancies). We were able to assess the performance of 24 out of the 131 models published to predict pre-eclampsia in 11 UK data sets. The models did not accurately predict the risk of pre-eclampsia across all UK data sets, and their performance varied within individual data sets. We developed new prediction models that showed promising performance on average across all data sets, but their ability to correctly identify women who develop pre-eclampsia varied between populations. The models were more clinically useful when used in the care of first-time mothers pregnant with one child, compared to a strategy of treating them all as if they were at high-risk of pre-eclampsia. WHAT DOES THIS MEAN?: Before using the International Prediction of Pregnancy Complications models in various populations, they need to be adjusted for characteristics of the particular population and the setting of application.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

The Upcoming Epidemic of Heart Failure in South Asia.

Currently, South Asia accounts for a quarter of the world population, yet it already claims ≈60% of the global burden of heart disease. Besides the epidemics of type 2 diabetes mellitus and coronary heart disease already faced by South Asian countries, recent studies suggest that South Asians may also be at an increased risk of heart failure (HF), and that it presents at earlier ages than in most other racial/ethnic groups. Although a frequently underrecognized threat, an eventual HF epidemic in the densely populated South Asian nations could have dramatic health, social and economic consequences, and urgent interventions are needed to flatten the curve of HF in South Asia. In this review, we discuss recent studies portraying these trends, and describe the mechanisms that may explain an increased risk of premature HF in South Asians compared with other groups, with a special focus on highly relevant features in South Asian populations including premature coronary heart disease, early type 2 diabetes mellitus, ubiquitous abdominal obesity, exposure to the world's highest levels of air pollution, highly prevalent pretransition forms of HF such as rheumatic heart disease, and underdevelopment of healthcare systems. Other rising lifestyle-related risk factors such as use of tobacco products, hypertension, and general obesity are also discussed. We evaluate the prognosis of HF in South Asian countries and the implications of an anticipated HF epidemic. Finally, we discuss proposed interventions aimed at curbing these adverse trends, management approaches that can improve the prognosis of prevalent HF in South Asian countries, and research gaps in this important field.

Availability and analytical quality of hemoglobin A1c point-of-care testing in general practitioners' offices are associated with better glycemic control in type 2 diabetes.

Background It is not clear if point-of-care (POC) testing for hemoglobin A1c (HbA1c) is associated with glycemic control in type 2 diabetes. Methods In this cross-sectional study, we linked general practitioner (GP) data on 22,778 Norwegian type 2 diabetes patients to data from the Norwegian Organization for Quality Improvement of Laboratory Examinations. We used general and generalized linear mixed models to investigate if GP offices' availability (yes/no) and analytical quality of HbA1c POC testing (average yearly "trueness score", 0-4), as well as frequency of participation in HbA1c external quality assurance (EQA) surveys, were associated with patients' HbA1c levels during 2014-2017. Results Twenty-eight out of 393 GP offices (7%) did not perform HbA1c POC testing. After adjusting for confounders, their patients had on average 0.15% higher HbA1c levels (95% confidence interval (0.04-0.27) (1.7 mmol/mol [0.5-2.9]). GP offices participating in one or two yearly HbA1c EQA surveys, rather than the maximum of four, had patients with on average 0.17% higher HbA1c levels (0.06, 0.28) (1.8 mmol/mol [0.6, 3.1]). For each unit increase in the GP offices' HbA1c POC analytical trueness score, the patients' HbA1c levels were lower by 0.04% HbA1c (-0.09, -0.001) (-0.5 mmol/mol [-1.0, -0.01]). Conclusions Novel use of validated patient data in combination with laboratory EQA data showed that patients consulting GPs in offices that perform HbA1c POC testing, participate in HbA1c EQA surveys, and maintain good analytical quality have lower HbA1c levels. Accurate HbA1c POC results, available during consultations, may improve diabetes care.

Exploring the relationship between coronary heart disease and type 2 diabetes: a cross-sectional study of secondary prevention among diabetes patients.

BACKGROUND: Coronary heart disease (CHD) and stroke are the major causes of death among people with diabetes. AIM: To describe the prevalence and onset of CHD and stroke among patients with type 2 diabetes mellitus (T2DM) in primary care in Norway, and explore the quality of secondary prevention. DESIGN & SETTING: A cross-sectional study of data was undertaken from electronic medical records (EMRs) of 10 255 patients with T2DM in general practice. The study took place in five counties of Norway (Oslo, Akershus, Rogaland, Hordaland, and Nordland). Quality of care was assessed based on national guideline recommendations. METHOD: Summary statistics with adjustments and binary logistic regression models were used. RESULTS: In total, 2260 patients (22.1%) had CHD and 759 (7.4%) had stroke. South Asians had significantly more CHD than ethnic Norwegians (29.5%, 95% confidence interval [CI] = 26.1 to 33.0 versus 21.5%, CI = 20.6 to 22.3) and other ethnic groups, and experienced onset of CHD or stroke at a mean of 7 years before Norwegians. In 47.9% of the patients, CHD was diagnosed before T2DM. Treatment target for low-density lipoprotein (LDL) cholesterol was reached for 30.0% and for systolic blood pressure (SBP) for 65.1% of the patients with CHD. Further, 20.9% of patients with CHD were present smokers, and only 5.0% of patients reached all four treatment targets (no smoking, HbA1c ≤7.0%, SBP <135 mmHg, LDL-cholesterol <1.8 mmol/l). CONCLUSION: The diagnosis of CHD preceded the diagnosis of T2DM in half of the patients. The prevalence of CHD was highest and onset earlier among ethnic South Asians. More intensive treatment of lipids, blood pressure, and smoking are needed in patients with T2DM and CHD.

Epidemiology, risk factors, and opportunities for prevention of cardiovascular disease in individuals of South Asian ethnicity living in Europe.

South Asian (SA) individuals represent a large, growing population in a number of European countries. These individuals, particularly first-generation SA immigrants, are at higher risk of developing type 2 diabetes, atherogenic dyslipidaemia, and coronary heart disease than most other racial/ethnic groups living in Europe. SAs also have an increased risk of stroke compared to European-born individuals. Despite a large body of conclusive evidence, SA-specific cardiovascular health promotion and preventive interventions are currently scarce in most European countries, as well as at the European Union level. In this narrative review, we aim to increase awareness among clinicians and healthcare authorities of the public health importance of cardiovascular disease among SAs living in Europe, as well as the need for tailored interventions targeting this group - particularly, in countries where SA immigration is a recent phenomenon. To this purpose, we review key studies on the epidemiology and risk factors of cardiovascular disease in SAs living in the United Kingdom, Italy, Spain, Denmark, Norway, Sweden, and other European countries. Building on these, we discuss potential opportunities for multi-level, targeted, tailored cardiovascular prevention strategies. Because lifestyle interventions often face important cultural barriers in SAs, particularly for first-generation immigrants; we also discuss features that may help maximise the effectiveness of those interventions. Finally, we evaluate knowledge gaps, currently available risk stratification tools such as QRISK-3, and future directions in this important field.

Are general practitioners characteristics associated with the quality of type 2 diabetes care in general practice? Results from the Norwegian ROSA4 study from 2014.

OBJECTIVE: To explore the associations between general practitioners (GPs) characteristics such as gender, specialist status, country of birth and country of graduation and the quality of care for patients with type 2 diabetes (T2DM). DESIGN: Cross-sectional survey. SETTING AND SUBJECTS: The 277 GPs provided care for 10082 patients with T2DM in Norway in 2014. The GPs characteristics were self-reported: 55% were male, 68% were specialists in General Practice, 82% born in Norway and 87% had graduated in Western Europe. Of patients, 81% were born in Norway and 8% in South Asia. Data regarding diabetes care were obtained from electronic medical records and manually verified. MAIN OUTCOME MEASURES: Performance of recommended screening procedures, prescribed medication and level of HbA1c, blood pressure and LDL-cholesterol stratified according to GPs characteristics, adjusted for patient and GP characteristics. RESULT: Female GPs, specialists, GPs born in Norway and GPs who graduated in Western Europe performed recommended procedures more frequently than their counterparts. Specialists achieved lower mean HbA1c (7.14% vs. 7.25%, p < 0.01), a larger proportion of their patients achieved good glycaemic control (HbA1c = 6.0%-7.0%) (49.1% vs. 44.4%, p = 0.018) and lower mean systolic blood pressure (133.0 mmHg vs. 134.7 mmHg, p < 0.01) compared with non-specialists. GPs who graduated in Western Europe achieved lower diastolic blood pressure than their counterparts (76.6 mmHg vs. 77.8 mmHg, p < 0.01). CONCLUSION: Several quality indicators for type 2 diabetes care were better if the GPs were specialists in General Practice. Key Points Research on associations between General Practitioners (GPs) characteristics and quality of care for patients with type 2 diabetes is limited. Specialists in General Practice performed recommended procedures more frequently, achieved better HbA1c and blood pressure levels than non-specialists. GPs who graduated in Western Europe performed screening procedures more frequently and achieved lower diastolic blood pressure compared with their counterparts. There were few significant differences in the quality of care between GP groups according to their gender and country of birth.

Effects of applying universal fetal growth standards in a Scandinavian multi-ethnic population.

INTRODUCTION: The question of whether universal growth charts can be used in multi-ethnic settings is of general interest. The Intergrowth-21st fetal growth and newborn size standards are suggested to represent optimal fetal growth regardless of country origin. Our aim was to examine whether women fulfilling the strict Intergrowth-21st inclusion criteria were healthier, showed less ethnic differences in fetal growth and newborn size, and less adverse perinatal outcomes. MATERIAL AND METHODS: Data were drawn from a population-based multi-ethnic cohort of 823 presumably healthy pregnant women in Oslo, Norway. We assessed differences in fetal and neonatal gestational age specific z-scores and compared maternal health parameters, pregnancy and birth complications between pregnancies fulfilling and not fulfilling the Intergrowth-21st criteria. RESULTS: Only 21% of pregnancies enrolled in our cohort fulfilled the Intergrowth-21st criteria. Fetal growth deviated substantially from the new standards, in particular for ethnic Europeans. Ethnic differences persisted in pregnancies fulfilling the criteria. In South Asian fetuses, estimated fetal weight was -0.60 SD (95% confidence interval -1.00, -0.20) lower at 24 gestational weeks, and birthweight was -0.62 SD (-0.95, -0.29) lower, compared with ethnic Europeans. Corresponding numbers for Middle-East/North Africans were -0.13 (-0.62, 0.36) and -0.60 (-1.00, -0.20). Maternal health indicators and birth complications were similar in women fulfilling and not fulfilling the criteria, but the relation depended on ethnic origin. CONCLUSIONS: In an urban multi-ethnic Norwegian population, applying an extensive list of criteria to define "healthy" pregnancies excludes the majority of women but does not cancel ethnic differences in fetal growth.

Vitamin D levels during pregnancy and associations with birth weight and body composition of the newborn: a longitudinal multiethnic population-based study.

We investigated associations between serum 25-hydroxyvitamin D (25(OH)D) in pregnancy and birth weight and other neonatal anthropometric measures. The present study was a population-based, multiethnic cohort study of 719 pregnant women (59 % ethnic minorities) in Oslo, Norway, delivering a singleton neonate at term and with birth weight measurements. In a representative sample, anthropometric measurements were taken. Maternal 25(OH)D was measured at gestational weeks 15 and 28. Women with 25(OH)D <37 nmol/l were recommended vitamin D3 supplementation. Separate linear regression analyses were performed to model the associations between 25(OH)D and each of the outcomes: birth weight, crown-heel length, head circumference, abdominal circumference, sum of skinfolds, mid-upper arm circumference and ponderal index. In early pregnancy, 51 % of the women were vitamin D deficient (25(OH)D<50 nmol/l). In univariate analyses and in models adjusting for maternal age, parity, education, prepregnancy BMI, season, gestational age and neonate sex, maternal 25(OH)D was significantly associated with birth weight, head circumference, abdominal circumference and ponderal index (P<0·05 for all), when used as a continuous variable and categorised (consistently low, consistently high, increasing and decreasing level). However, after adjusting for ethnicity, 25(OH)D was no longer associated with any of the outcomes. Sex-specific associations for abdominal circumference and sum of skinfolds were found (P for interaction<0·05). In conclusion, in a multiethnic cohort of pregnant women with high prevalence of vitamin D deficiency, we found no independent relation between maternal vitamin D levels and any of the neonatal anthropometric measures, and the strong association between ethnicity and neonatal outcomes was not affected by maternal vitamin D status.

Vitamin D deficiency and supplementation in pregnancy in a multiethnic population-based cohort.

BACKGROUND: To investigate ethnic differences in vitamin D levels during pregnancy, assess risk factors for vitamin D deficiency and explore the effect of vitamin D supplementation in women with deficiency in early pregnancy. METHODS: This is a population-based, multiethnic cohort study of pregnant women attending Child Health Clinics for antenatal care in Oslo, Norway. Serum-25-hydroxyvitamin D [25(OH)D] was measured in 748 pregnant women (59% ethnic minorities) at gestational weeks (GW) 15 (SD:3.6) and 28 (1.4). Women with 25(OH)D <37 nmol/L at GW 15 were for ethical reasons recommended vitamin D3 supplementation. Main outcome measure was 25(OH)D, and linear regression models were performed. RESULTS: Severe deficiency (25(OH)D <25 nmol/L) was found at GW 15 in 45% of women from South Asia, 40% from the Middle East and 26% from Sub-Saharan Africa, compared to 2.5% in women from East Asia and 1.3% of women from Western Europe. Women from South Asia, the Middle East and Sub-Saharan Africa had mean values that were -28 (95 % CI:-33, -23), -24 (-29, -18) and -20 (-27, -13) nmol/L lower than in Western women, respectively. Ethnicity, education, season and intake of vitamin D were independently associated with 25(OH)D. At GW 28, the mean 25(OH)D had increased from 23 (SD:7.8) to 47 (27) nmol/L (p < 0.01) in women who were recommended vitamin D supplementation, with small or no change in women with sufficient vitamin D levels at baseline. CONCLUSIONS: Vitamin D deficiency was prevalent among South Asian, Middle Eastern and African women. The serum levels of 25(OH)D increased significantly from GW 15 to 28 in vitamin D deficient women who received a recommendation for supplementation. This recommendation of vitamin D supplementation increased vitamin D levels in deficient women.

Ethnic differences in BMI, subcutaneous fat, and serum leptin levels during and after pregnancy and risk of gestational diabetes.

OBJECTIVE: To explore the differences between Europeans and South Asians in BMI, subcutaneous fat, and serum leptin (s-leptin) levels during and after pregnancy and their relationship with gestational diabetes (GDM). DESIGN: Multi-ethnic population-based cohort study, whereof 353 Europeans (93.1% of the included) and 190 South Asians (95.0% of the included). METHODS: S-leptin, BMI, and subcutaneous fat (sum of triceps, subscapular, and suprailiac skinfolds) were measured at 14 and 28 weeks of gestation, and 14 weeks after delivery. GDM was diagnosed with the WHO criteria 2013. RESULTS: South Asians had similar thickness of the triceps and suprailiac skinfolds, thicker subscapular skinfold, and higher s-leptin than Europeans in early pregnancy, despite lower BMI. South Asians retained more subcutaneous fat (mean (95% CI) 10.0 (7.4-12.7) mm vs 3.8 (1.9-5.8) mm) and BMI (1.5 (1.2-1.8) kg/m(2) vs 0.1 (-0.1 to 0.3) kg/m(2)) than Europeans 14 weeks after delivery and s-leptin decreased less in South Asians than Europeans (-0.13 (-0.27 to -0.00) µg/l vs -0.47 (-0.57 to -0.37) µg/l, P<0.001 for all). The prevalence of GDM was 23.8% (n=84) in Europeans and 42.6% (n=81) in South Asians. BMI, subcutaneous fat, and s-leptin were all positively associated with GDM, also after adjustment for covariates. CONCLUSIONS: The relatively high amounts of subcutaneous fat and s-leptin in South Asians in early pregnancy contributed to their increased risk of GDM. South Asians retained more weight and subcutaneous fat after delivery, potentially increasing their risk of adiposity and GDM in future pregnancies.