Registry-based randomised clinical trials: a remedy for evidence-based diabetes care?

This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirements and limited entry of novel candidate drugs. There is a need for novel and cost-effective paradigms of clinical development to meet these and other challenges. The concept of registry-based randomised clinical trials (RRCTs) is an attractive option. In this review we focus on type 2 diabetes and the prevention of cardiovascular and microvascular comorbidities and mortality, using the Swedish SMARTEST trial as an example of an RRCT. We also give some examples from other disease areas. The RRCT concept is a novel, cost-effective and scientifically sound approach for conducting large-scale diabetes trials in a real-world setting.

GWAS in people of Middle Eastern descent reveals a locus protective of kidney function-a cross-sectional study.

BACKGROUND: Type 2 diabetes is one of the leading causes of chronic kidney failure, which increases globally and represents a significant threat to public health. People from the Middle East represent one of the largest immigrant groups in Europe today. Despite poor glucose regulation and high risk for early-onset insulin-deficient type 2 diabetes, they have better kidney function and lower rates of all-cause and cardiovascular-specific mortality compared with people of European ancestry. Here, we assessed the genetic basis of estimated glomerular filtration rate (eGFR) and other metabolic traits in people of Iraqi ancestry living in southern Sweden. METHODS: Genome-wide association study (GWAS) analyses were performed in 1201 Iraqi-born residents of the city of Malmö for eGFR and ten other metabolic traits using linear mixed-models to account for family structure. RESULTS: The strongest association signal was detected for eGFR in CST9 (rs13037490; P value = 2.4 × 10-13), a locus previously associated with cystatin C-based eGFR; importantly, the effect (major) allele here contrasts the effect (minor) allele in other populations, suggesting favorable selection at this locus. Additional novel genome-wide significant loci for eGFR (ERBB4), fasting glucose (CAMTA1, NDUFA10, TRIO, WWC1, TRAPPC9, SH3GL2, ABCC11), quantitative insulin-sensitivity check index (METTL16), and HbA1C (CAMTA1, ME1, PAK1, RORA) were identified. CONCLUSIONS: The genetic effects discovered here may help explain why people from the Middle East have better kidney function than those of European descent. Genetic predisposition to preserved kidney function may also underlie the observed survival benefits in Middle Eastern immigrants with type 2 diabetes.

Insulin action and secretion independent of traditional risk factors predict new-onset type 2 diabetes in Iraqi and Swedish born citizens - The MEDIM cohort study.

AIMS: Our aim was to study the incidence of type 2 diabetes in a population-based cohort of Swedish and Iraqi born individuals, focussing on traditional risk factors, insulin action, insulin secretion and ethnicity. MATERIALS AND METHODS: The cohort consisted of 1164 Iraqi and 693 Swedish-born citizens. We investigated the association between new-onset type 2 diabetes and the predictors including lifestyle factors, metabolic risk markers, country of birth, insulin sensitivity and secretion assessed by Matsuda index with Cox regression. RESULTS: Eighty-nine individuals were diagnosed with type 2 diabetes with a mean follow-up of 7.5 years. Both lower insulin sensitivity (ISI, HR 0.02 [0.01-0.08]) as well as insulin secretion (CIR, HR 0.13 [0.07-0.24]) at baseline predicted type 2 diabetes onset, independent of traditional risk factors. Our results were not modified by country of birth. Regarding traditional risk factors, WHR (1.05 [1.00-1.09]), blood glucose (3.27 [2.35-4.55]), LDL/HDL (1.46 [1.20-1.78]) and diastolic blood pressure (1.04 [1.00-1.07]) predicted diabetes incidence in the full model. CONCLUSIONS: Both impaired insulin sensitivity index and corrected insulin response predicted type 2 diabetes onset, independent of traditional risk factors. We conclude that insulin secretion and action might be useful additional predictors for type 2 diabetes in populations of European and Middle Eastern ethnicities.

The effect of a randomised controlled lifestyle intervention on weight loss and plasma proneurotensin.

AIMS: Proneurotensin (Pro-NT) is a strong predictor of cardiometabolic disease including type 2 diabetes and obesity, however, the effect of lifestyle change on Pro-NT has not been investigated in this context. Middle Eastern (ME) immigrants represent the largest and fastest growing minority population in Europe and are a high-risk population for obesity and type 2 diabetes. In this randomised controlled lifestyle intervention (RCT) addressing ME immigrants to Sweden where weight-loss was previously studied as the main outcome, as a secondary analysis we aimed to study change in Pro-NT during follow-up and if baseline Pro-NT predicted weight loss. METHODS: Immigrants from the Middle East at high risk for type 2 diabetes were invited to participate in this RCT adapted lifestyle intervention of four months' duration. The intervention group (N = 48) received a culturally adapted lifestyle intervention comprising seven group sessions and a cooking class addressing healthier diet and increased physical activity. The control group (N = 44) received treatment as usual with information to improve lifestyle habits on their own. Data assessed using mixed effects regression. OUTCOMES: Primary outcome; change in Pro-NT. Secondary outcome; change in BMI in relation to baseline plasma concentration of Pro-NT. RESULTS: During the four months follow up, weight was significantly reduced in the intervention (-2.5 kg) compared to the control group (0.8 kg) (ß -0.12, 95% CI -0.24 to -0.01, P = 0.028). Pro-NT increased to a significantly greater extent in the intervention compared to the control group during follow up (28.2 vs. 3.5 pmol/L) (ß 11.4; 4.8 to 18.02, P < 0.001). Change over time in BMI was associated with baseline Pro-NT (ß 0.02; 0.01 to 0.04, P = 0.041). CONCLUSION: In consistence with data from surgical weight loss, this RCT paradoxically shows increased levels of Pro-NT during a multifactorial lifestyle intervention resulting in weight loss. Long term studies of Pro-NT following weight loss are needed. TRIAL REGISTRATION: This study is a secondary analysis of the RCT trial registered at www. CLINICALTRIALS: gov . REGISTRATION NUMBER: NCT01420198. Date of registration 19/08/2011. The performance and results of this trial conform to the CONSORT 2010 guidelines.

Postprandial triglyceride levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants.

PURPOSE: Previous studies have shown that at a similar body mass index, Middle Eastern immigrants are more insulin resistant and at higher risk for type 2 diabetes (T2D) than native Europeans. Insulin resistance is strongly associated with disturbed fat metabolism and cardiovascular disease (CVD). However, fat metabolism is poorly investigated comparing Middle Eastern and European ethnicities. METHODS: This observational study included 26 Iraqi and 16 Swedish-born men without T2D or clinical risk factors for CVD. An oral fat tolerance test (OFTT) was performed, where plasma triglycerides (p-TG) were measured for 6 h. mRNA expression and adipocyte size were measured in subcutaneous adipose tissue biopsies collected prior to OFTT, and magnetic resonance imaging was conducted to assess body fat distribution. RESULTS: The median p-TG accumulation was higher and the clearance slower among Iraqis than Swedes. None of the groups reached their fasting p-TG (Iraqis 1.55 mmol/l; Swedes 0.95 mmol/l) after 6 h (Iraqis p-TG 3.10 mmol/l; Swedes p-TG 1.50 mmol/l). Adipocyte size, mRNA expression, and fat accumulation in the liver, muscle and abdomen were similar in both groups. CONCLUSION: Postprandial p-TG levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants without CVD risk factors.

Type 2 diabetes burden among migrants in Europe: unravelling the causal pathways.

European populations are ethnically and culturally diverse due to international migration. Evidence indicates large ethnic inequalities in the prevalence of type 2 diabetes. This review discusses the burden of type 2 diabetes and its related complications, and the potential explanatory mechanisms among migrants in Europe. The current available data suggest that the rate of type 2 diabetes is higher in all migrant groups and that they develop this disease at an earlier age than the host European populations. The level of diabetes awareness among migrant populations is high, but glycaemic control remains suboptimal compared with Europeans. The culturally adapted lifestyle modification intervention trials to prevent type 2 diabetes mainly focus on South Asian adults in Europe. Diabetes-related microvascular and macrovascular complications remain a major burden among migrant populations in Europe. Earlier studies found higher mortality rates among migrants, but recent studies seem to suggest a shifting trend in favour of first-generation migrants. However, the extent of the burden of type 2 diabetes varies across migrant groups and European countries. Despite the higher burden of type 2 diabetes among migrants, the key underlying factors are not well understood mainly due to limited investment in basic science research and development of prospective cohort studies. We hypothesise that the underlying risk factors for the high burden of type 2 diabetes and its related complications in migrants are multifaceted and include pre-migration factors, post-migration factors and genetic predispositions. Given the multi-ethnic nature of the current European population, there is a clear need for investment in research among migrant populations to gain insight into factors driving the high burden of type 2 diabetes and related complications to facilitate prevention and treatment efforts in Europe.

Mortality in first- and second-generation immigrants to Sweden diagnosed with type 2 diabetes: a 10 year nationwide cohort study.

AIMS/HYPOTHESIS: Non-Western immigrants to Europe are at high risk for type 2 diabetes. In this nationwide study including incident cases of type 2 diabetes, the aim was to compare all-cause mortality (ACM) and cause-specific mortality (CSM) rates in first- and second-generation immigrants with native Swedes. METHODS: People living in Sweden diagnosed with new-onset pharmacologically treated type 2 diabetes between 2006 and 2012 were identified through the Swedish Prescribed Drug Register. They were followed until 31 December 2016 for ACM and until 31 December 2012 for CSM. Analyses were adjusted for age at diagnosis, sex, socioeconomic status, education, treatment and region. Associations were assessed using Cox regression analysis. RESULTS: In total, 138,085 individuals were diagnosed with type 2 diabetes between 2006 and 2012 and fulfilled inclusion criteria. Of these, 102,163 (74.0%) were native Swedes, 28,819 (20.9%) were first-generation immigrants and 7103 (5.1%) were second-generation immigrants with either one or both parents born outside Sweden. First-generation immigrants had lower ACM rate (HR 0.80 [95% CI 0.76, 0.84]) compared with native Swedes. The mortality rates were particularly low in people born in non-Western regions (0.46 [0.42, 0.50]; the Middle East, 0.41 [0.36, 0.47]; Asia, 0.53 [0.43, 0.66]; Africa, 0.47 [0.38, 0.59]; and Latin America, 0.53 [0.42, 0.68]). ACM rates decreased with older age at migration and shorter stay in Sweden. Compared with native Swedes, first-generation immigrants with ≤ 24 years in Sweden (0.55 [0.51, 0.60]) displayed lower ACM rates than those spending >24 years in Sweden (0.92 [0.87, 0.97]). Second-generation immigrants did not have better survival rates than native Swedes but rather displayed higher ACM rates for people with both parents born abroad (1.28 [1.05, 1.56]). CONCLUSIONS/INTERPRETATION: In people with type 2 diabetes, the lower mortality rate in first-generation non-Western immigrants compared with native Swedes was reduced over time and was equalised in second-generation immigrants. These findings suggest that acculturation to Western culture may impact ACM and CSM in immigrants with type 2 diabetes but further investigation is needed. Graphical abstract.

Adult-onset diabetes in Middle Eastern immigrants to Sweden: Novel subgroups and diabetic complications-The All New Diabetes in Scania cohort diabetic complications and ethnicity.

BACKGROUND: Middle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro- and microvascular complications between diabetes patients of Middle Eastern and European origin. METHODS: This study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro- and microvascular complications were assessed using cox-regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c. FINDINGS: In Iraqi immigrants versus native Swedes, severe insulin-deficient diabetes was almost twice as common (27.9 vs. 16.2% p < 0.001) but severe insulin-resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06-3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05-0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group. INTERPRETATION: People with diabetes, born in the Middle East present with a more insulin-deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications.

Pro-Enkephalin and its association with renal function in Middle Eastern immigrants and native Swedes.

Iraqi-born immigrants residing in Sweden exhibit lower blood pressure as well as better renal function despite an overall worse metabolic risk profile in comparison with native Swedes. This may indicate the presence of cardiorenal protective mechanisms in the Middle Eastern population. Hence, the aim of this study was to investigate whether the association between renal function and Pro-Enkephalin (PENK), a biomarker predictive of both acute and chronic kidney dysfunction, differs across ethnicities. The MEDIM population-based study including a cohort of women and men, born in Iraq or Sweden, aged 30-75 years was conducted in Malmö, Sweden, from 2010 to 2012. The study included fasting blood samples, physical examinations and self-administrated questionnaires. Despite significantly better renal function assessed by creatinine-based eGFR in the Iraqi group, levels of PENK did not differ between the groups, (70.0 pmol/L, born in Iraq (n = 1263) vs 71.1, born in Sweden (n = 689), p = .4). However, the association between PENK and renal function was relatively weaker in the Iraqi born group, as supported by a significant interaction between PENK and country of birth (PInteraction= Country of birth x PENK = 0,010). This observational study suggests that the association between renal function and PENK was weaker in Middle Eastern immigrants. This is of interest as PENK may exhibit a direct effect on renal function, however further research is needed including studies on causality.

Magnitude of rise in proneurotensin is related to amount of triglyceride appearance in blood after standardized oral intake of both saturated and unsaturated fat.

BACKGROUND: In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown. AIM: To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals. SETTING/ METHODS: Twenty-two healthy subjects were given 150 mL of full milk cream (54 g fat) and 59 mL of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood was drawn at fasted before 0 h (h) and at 1 h, 2 h and 4 h after ingestion. Post-ingested values of proneurotensin and plasma triglycerides were compared with fasting levels and post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with that of plasma triglycerides. RESULTS: An immediate rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 h for proneurotensin [mean (95% confidence interval)] of 22 (12-31) pmol/L (P < 0.001) and at 3 h for triglycerides of 0.60 (0.43-0.78) mmol/L (P < 0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 h of 62 (46-78) pmol/L (P < 0.001) and plasma triglycerides at 3 h of 0.32 (0.18-0.45) mmol/L (P < 0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r = 0.49, P = 0.021) and olive oil (r = 0.55, P = 0.008), respectively. CONCLUSION: Proneurotensin increases after an oral lipid load of both cream and olive oil and the rise of post-ingestion plasma triglycerides is significantly related to the rise of post-ingestion proneurotensin.

Cardiovascular risk assessment in South and Middle-East Asians living in the Western countries.

Nearly a quarter of the world population lives in the South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and the Maldives). Due to rapid demographic and epidemiological transition in these countries, the burden of non-communicable diseases is growing, which is a serious public health concern. Particularly, the prevalence of pre-diabetes, diabetes and atherosclerotic cardiovascular disease (CVD) is increasing. South Asians living in the West have also substantially higher risk of CVD and mortality compared with white Europeans and Americans. Further, as a result of global displacement over the past three decades, Middle-Eastern immigrants now represent the largest group of non-European immigrants in Northern Europe. This vulnerable population has been less studied. Hence, the aim of the present review was to address cardiovascular risk assessment in South Asians (primarily people from India, Pakistan and Bangladesh), and Middle-East Asians living in Western countries compared with whites (Caucasians) and present results from some major intervention studies. A systematic search was conducted in PubMed to identify major cardiovascular health studies of South Asian and Middle-Eastern populations living in the West, relevant for this review. Results indicated an increased risk of CVD. In conclusion, both South Asian and Middle-Eastern populations living in the West carry significantly higher risk of diabetes and CVD compared with native white Europeans. Lifestyle interventions have been shown to have beneficial effects in terms of reduction in the risk of diabetes by increasing insulin sensitivity, weight loss as well as better glycemic and lipid control.

Effects of a randomized, culturally adapted, lifestyle intervention on mental health among Middle-Eastern immigrants.

BACKGROUND: Middle-Eastern immigrants in Sweden are at increased risk for type 2 diabetes (T2D) and poor mental health. Physical activity not only prevents/delays onset of T2D but also shows favorable effects on mental health. However, the effects of a culturally adapted lifestyle intervention on mental health among Middle-Eastern immigrants have not been explored before. We aimed to study the effects of a randomized controlled, culturally adapted lifestyle intervention on anxiety and depression levels in diabetes-prone Iraqi immigrants. METHODS: Participants (n = 96) were randomized to intervention group, IG (n = 50) or control group, CG (n = 46). The IG received seven group sessions addressing lifestyle change and the CG received treatment as usual. Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Hospital Anxiety and Depression Scale (HADS) assessed mental health at start, mid (2 months) and end of the study (4 months). Proportional odds ratio (OR) model was used to study the effect of the intervention. RESULTS: The odds of scoring lower on MADRS-S and HADS depression scale at visit 3 vs. baseline were higher in the IG compared to the CG (MADRS-S OR 5.9, 95% CI: 1.6-22.5; HADS OR 4.4, 95% CI: 0.9-20.3). The findings persisted after adjustment for age, sex, body mass index, time since migration, sedentary lifestyle and language spoken at home. Group differences were non-significant at visit 2 vs. baseline. CONCLUSION: A culturally adapted lifestyle intervention addressing T2D prevention in Middle-Eastern immigrants has favorable effects on mental health. The effect was more pronounced at the 4 months than at 2 months follow-up, indicating beneficial effect of longer study duration. TRIAL REGISTRATION: www.clinicaltrials.gov NCT01420198.

Self-rated health and social capital in Iraqi immigrants to Sweden: The MEDIM population-based study.

OBJECTIVES: Poor self-rated health is an estimator of quality of life and a predictor of mortality seldom studied in immigrant populations. This work aimed to study self-rated health in relation to social capital, socioeconomic status, lifestyle and comorbidity in immigrants from Iraq - one of the largest non-European immigrant group in Sweden today - and to compare it with the self-rated health of native Swedes. DESIGN: The study was a cross-sectional population-based study conducted from 2010 to 2012 among citizens of Malmö, Sweden, aged 30-65 years and born in Iraq or Sweden. All participants underwent a health examination and answered questionnaires on self-rated health, social capital, comorbidity, lifestyle and socioeconomic status. RESULTS: In total, 1348 Iraqis and 677 Swedes participated. Poor self-rated health was identified in 43.9% of Iraqis and 21.9% of native Swedes ( p<0.001), with the highest prevalence (55.5%) among Iraqi women. Low social capital was highly prevalent in the immigrants. Female gender showed higher odds of poor self-rated health in Iraqis than in Swedes (OR 1.8, 95% CI 1.4-2.5, pinteraction=0.024), independent of other risk factors connected to social capital, socioeconomic status, lifestyle or comorbidity. CONCLUSIONS: Although public health initiatives promoting social capital, socioeconomic status and comorbidity in immigrants are crucial, the excess risk of poor self-rated health in Iraqi women is not fully attributed to known risk factors for self-rated health, but remains to be further explored.

Changes in dietary intake following a culturally adapted lifestyle intervention among Iraqi immigrants to Sweden at high risk of type 2 diabetes: a randomised trial.

OBJECTIVE: To investigate the effectiveness of a culturally adapted lifestyle intervention for changing dietary intake, particularly energy, fat and fibre intakes, in the intervention group (IG) compared with the control group (CG). DESIGN: Randomised controlled trial. SETTING: IG (n 50) and CG (n 46). The IG was offered seven group sessions, including one cooking class, over a period of 4 months. The participants filled out 4 d food diaries at the start, mid and end of the study. SUBJECTS: Iraqi-born residents of Malmö, Sweden, at increased risk for developing diabetes. RESULTS: At baseline, participants' fat intake was high (40 % of total energy intake (E%)). The predefined study goals of obtaining <30 E% from fat and ≥15 g fibre/4184 kJ (1000 kcal) were met by very few individuals. In the IG v. the CG, the proportion of individuals obtaining <40 E% from fat (48·4 v. 34·6 %, P=0·65), <10 E% from saturated fat (32·3 v. 11·5 %, P=0·14) and ≥10 g fibre/4184 kJ (45·2 v. 26·9 %, P=0·46) appeared to be higher at the last visit, although the differences were statistically non-significant. A trend towards decreased mean daily intakes of total energy (P=0·03), carbohydrate (P=0·06), sucrose (P=0·02) and fat (P=0·02) was observed within the IG. Differences in changes over time between the groups did not reach statistical significance. CONCLUSIONS: Although no significant differences were observed in the two groups, our data indicate that this culturally adapted programme has the potential to modify dietary intake in Middle Eastern immigrants. The high fat intake in this group should be addressed.

BMI and waist circumference cut-offs for corresponding levels of insulin sensitivity in a Middle Eastern immigrant versus a native Swedish population - the MEDIM population based study.

BACKGROUND: The aim of this study was to identify corresponding body mass index (BMI) and waist circumference cut-offs for equivalent levels of insulin sensitivity in a Middle Eastern immigrant population compared with native Swedes. METHODS: Citizens of Malmö, Sweden aged 30 to 75 years, who were born in Iraq or Sweden, were in 2010-2012 invited to participate in a health examination including anthropometrics, oral glucose tolerance test, fasting samples and interviews concerning sociodemographic factors and lifestyle behaviours. RESULTS: In total, 1176 individuals born in Iraq and 688 born in Sweden, without previously diagnosed type 2 diabetes, participated in the study. In normal weight participants (BMI < 25 kg/m2), 21.2% of Iraqis vs 9.3% of Swedes were insulin resistant. Corresponding figures in participants without abdominal obesity (waist circumference, men < 94 cm, women < 80 cm) were 28.2% of Iraqis vs 9.4% of Swedes. The age-adjusted insulin sensitivity index (ISI) for obese Swedes (BMI 30 kg/m2) corresponded in Iraqi men with BMI of 28.5 kg/m2, and in Iraqi women with BMI of 27.5 kg/m2. The ISI level in abdominally obese Swedes corresponded with waist circumference cut-offs of 84.0 cm and 71.0 cm in Iraqi men and women, respectively. In men only, larger waist circumference (P interaction = 0.026) presented a stronger association with impaired ISI in Iraqis as compared to Swedes. CONCLUSIONS: Our data shows that the impact of BMI and waist circumference on ISI is ethnic- and gender-specific, indicating a disturbed fat metabolism in Iraqi males in particular. Our data suggests that 10 cm lower cut-off values for abdominal obesity, than is currently recommended by major organisations, should be considered when estimating diabetes risk in Middle Eastern populations.

Cross-cultural validation of a simple self-report instrument of physical activity in immigrants from the Middle East and native Swedes.

AIM: To investigate cross-cultural validity of a simple self-report instrument of physical activity intended to be used in Swedish health care. METHODS: A validation study performed in 599 Iraqis (58% men) and 553 Swedes (53% men) aged 30-75 years living in the city of Malmö, Sweden. The self-report instrument by the Swedish National Board of Health and Welfare was compared to corresponding measures assessed from accelerometry as reference. RESULTS: The agreement between the methods in assessing the participants as sufficiently/insufficiently physically active (cut-point 150 min/week) was 65% in the Iraqis and 52% in the Swedes (p<0.001). The proportion disagreement where the self-reported physical activity was sufficient but insufficient according to the accelerometry was 26% and 45% in Iraqis and Swedes, respectively. Physical activity time (min/week) was overestimated by self-report compared to accelerometry by 71% in the Iraqis and 115% in the Swedes (p<0.001). The smallest and largest overestimation was seen in Iraqi (57%) and Swedish (139%) women, respectively. The deviation of the self-report instrument compared to accelerometry was related to the physical activity level, as the overestimation mainly occurred at lower physical activity. CONCLUSIONS: The self-report instrument proposed by the Swedish National Board of Health and Welfare may overestimate the proportion sufficiently physically active, but to an extent depending on cultural background and gender.

Physical inactivity is strongly associated with anxiety and depression in Iraqi immigrants to Sweden: a cross-sectional study.

BACKGROUND: Increasing evidence on associations between mental health and chronic diseases like cardio-vascular disease and diabetes together with the fact that little is known about the prevalence of anxiety/depression and associated risk factors among Iraqi immigrants to Sweden, warrants a study in this group. The aim was to study the prevalence of anxiety and depression in immigrants from Iraq compared to native Swedes and compare socioeconomic and lifestyle-related factors associated with these conditions. METHOD: A population-based, cross-sectional study of residents of Malmö, Sweden, aged 30-75 years, born in Iraq or Sweden. The overall response rate was 49% for Iraqis and 32% for Swedes. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Associations were studied using multivariate logistic regression models. The outcome was odds of depression and/or anxiety. RESULTS: Compared to Swedes (n = 634), anxiety was three times as prevalent (52.6 vs. 16.3%, p < 0.001) and depression five times as prevalent (16.3 vs. 3.1%, p < 0.001) in Iraqi immigrants (n = 1255). Iraqis were three times more likely to be anxious and/or depressed compared to Swedes (odds ratio (OR) 3.02, 95% confidence interval (CI) 2.06-4.41). Among Iraqis, physical inactivity (<150 min/week) (OR 2.00, 95% CI 1.49-2.69), economic insecurity (OR 2.16, 95% CI 1.56-3.01), inability to trust people (OR 1.75, 95% CI 1.28-2.39) and smoking (OR 1.43, 95% CI 1.02-2.01), were strongly associated with anxiety/depression. Among Swedes, living alone (OR 2.10, 95% CI 1.36-3.25) and economic insecurity (OR 2.38, 95% CI 1.38-4.12) showed the strongest associations with anxiety/depression. Country of birth modified the effect of physical inactivity (P(interaction) =0.058) as well as of marital status (P(interaction) =0.001). CONCLUSION: Our study indicates that economic insecurity has a major impact on poor mental health irrespective of ethnic background but that physical inactivity may be more strongly associated with anxiety/depression in immigrants from the Middle East compared to native Swedes. Preventive actions emphasizing increased physical activity may reduce the risk of poor mental health in immigrants from the Middle East, however intervention studies are warranted to test this hypothesis.

Associations between birth weight and adult apolipoproteins: The LifeGene cohort.

BACKGROUND: Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort. METHODS: The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801). RESULTS: The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005). CONCLUSIONS: Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Previous SARS-CoV-2 infections and their impact on the protection from reinfection during the Omicron BA.5 wave - a nested case-control study among vaccinated adults in Sweden.

Objectives: We evaluated the protection afforded by SARS-CoV-2 infection-induced immunity against reinfection among working-age vaccinated individuals during a calendar period from June to December 2022 when Omicron BA.5 was the dominating subvariant in Scania County, Sweden. Methods: The study cohort (n = 71,592) mainly consisted of health care workers. We analyzed 4144 infected cases during the Omicron BA.5 dominance and 41,440 sex- and age-matched controls with conditional logistic regression. Results: The average protection against reinfection was marginal (16%, 95% confidence interval [CI] 7-23%) during the study period but substantially higher for recent infections. Recent infection (3-6 months) with Omicron BA.2 and BA.5 offered strong protection (86%, 95% CI 68-94% and 78%, 95% CI 69-84%), whereas more distant infection (6-12 months) with Omicron BA.1, BA.2, and the variants before Omicron offered marginal or no protection. Conclusions: These findings suggest that infection-induced immunity contributes to short-term population protection against infection with the subvariant BA.5 among working-age vaccinated individuals but wanes considerably with time, independent of the virus variant.

Cardiovascular disease in relation to diabetes status in immigrants from the Middle East compared to native Swedes: a cross-sectional study.

BACKGROUND: Type 2 diabetes is highly prevalent in immigrants to Sweden from Iraq, but the prevalence of cardiovascular disease (CVD) and its risk factors are not known. In this survey we aimed to compare the prevalence of CVD and CVD-associated risk factors between a population born in Iraq and individuals born in Sweden. METHODS: This population-based, cross-sectional study comprised 1,365 Iraqi immigrants and 739 Swedes (age 30-75 years) residing in the same socioeconomic area in Malmö, Sweden. Blood tests were performed and socio-demography and lifestyles were characterized. To investigate potential differences in CVD, odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by multivariate logistic regression analysis with adjustment for metabolic, lifestyle and psychosocial risk factors for CVD. Outcome measures were odds of CVD. RESULTS: There were no differences in self-reported prevalence of CVD between Iraqi- and Swedish-born individuals (4.0 vs. 5.5%, OR 0.9, 95% CI 0.4-1.8). However, the prevalence of type 2 diabetes was higher in Iraqi compared to Swedish participants (8.4 vs. 3.3%, OR = 4.2, 95% CI 2.6-6.7). Moreover, among individuals with type 2 diabetes, Iraqis had a higher prevalence of CVD (22.8 vs. 8.0%, OR = 4.2, 95% CI 0.9-20.0), after adjustment for age and sex. By contrast, among those without diabetes, immigrants from Iraq had a lower prevalence of CVD than Swedes (2.2 vs. 5.5%, OR = 0.6, 95% CI 0.3-0.9).Type 2 diabetes was an independent risk factor for CVD in Iraqis only (OR = 6.8, 95% CI 2.8-16.2). This was confirmed by an interaction between country of birth and diabetes (p = 0.010). In addition, in Iraqis, type 2 diabetes contributed to CVD risk to a higher extent than history of hypertension (standardized OR 1.5 vs. 1.4). CONCLUSIONS: This survey indicates that the odds of CVD in immigrants from Iraq are highly dependent on the presence or absence of type 2 diabetes and that type 2 diabetes contributes with higher odds of CVD in Iraqi immigrants compared to native Swedes. Our study suggests that CVD prevention in immigrants from the Middle East would benefit from prevention of type 2 diabetes.