Aspects of insulin secretion and action in Middle Eastern immigrants to Sweden

Background: Middle Eastern (ME) immigrants to Europe have a higher prevalence of type 2 diabetes (T2D) as compared to Europeans. Previous findings from the MEDIM population-based cohort (Impact of ethnicity and migration on diabetes in Malmö) have shown that ME immigrants are more insulin resistant before developing T2D as compared to native Swedes. However, knowledge is still lacking if there are differences across ethnicities on how insulin secretion and action change with increasing age. Furthermore, T2D is linked to an increased incidence of cancer, cardiovascular disease (CVD), and allcause
mortality (ACM) but differences in incidence rates across ethnicities remain unknown. Vitamin D deficiency is linked to metabolic disturbances, but knowledge concerning differences in the associations between vitamin D (25(OH)D) and glucose regulation across ME and European ethnicities
is still unknown.
Aims: In the MEDIM cohort: 1) study changes in insulin action (assessed by insulin sensitivity index (ISI)) and secretion (assessed by oral disposition index (DIo)), with increasing age, and the potential impact of ethnicity, 2) In an 8-year register based follow up of the MEDIM cohort, study ethnic differences in the incidence of ACM, cancer- and CVD, as well as case-specific mortality (CSM). 3)
Study differences across ethnicities in the levels of 25(OH)D and PTH, and if differences in glucose regulation are explained by 25(OH)D and PTH. In the MEDIM culturally adapted randomized controlled trial (RCT): 4) to study the effect of lifestyle intervention in ME immigrants on the levels of 25(OH)D,
insulin-like growth factor 1 (IGF-1), Pro-neurotensin (Pro-NT) and adiponectin, and whether the effect of the intervention on ISI and DIo is mediated by these hormones.
Methods: Residents of Malmö, born in Iraq or Sweden aged 30-75 years old, were invited to participate in the MEDIM study between 2010-2012. Oral glucose tolerance tests were performed (0,30,60,120 min) to calculate ISI and DIo using the Matsuda formula. In paper I, we studied changes in ISI and DIo
with increasing age. Associations were studied using multiple linear regression analysis. In paper II, we conducted an 8 year follow-up where register data were retrieved from baseline until the 31st of December 2018 to assess the adjusted hazard ratios (HR) for the relationships between ethnicity, ACM, cancer, CVD events and CSM. In paper III, in the MEDIM cohort, multiple regression analysis
was assessed to study the potential associations between 25(OH)D, ISI and DIo across ethnicities. In paper IV, Iraqi immigrants at high risk of T2D were invited to participate in the MEDIM culturally adapted intervention RCT. We used mixed model regression analysis to study whether the effect of the intervention was mediated by the changes in the levels of IGF-1, 25(OH)D, Pro-NT or adiponectin.
Results: Our data show that 1) ISI and DIo decreased with increasing age regardless of ethnicity with the Iraqis having lower ISI in all age groups 2) The adjusted ACM, cancer, CVD and CSM rates were
lower among Iraqi immigrants compared to native Swedes. 3) The levels of 25(OH)D were significantly lower and the levels of PTH were higher among Iraqi immigrants compared to native Swedes. The lower levels of ISI in Iraqis compared to Swedes were explained by differences in 25(OH)D. 4) The
effects of lifestyle intervention on ISI and DIo were associated with changes in the levels of 25(OH)D.
Conclusion: This thesis shows a high risk of earlier diabetes onset in Iraqi immigrants as reflected by lower insulin sensitivity in corresponding age categories and worse glucose regulation over time.