Differences in insulin sensitivity, lipid metabolism and inflammation between young adult Pakistani and Norwegian patients with type 2 diabetes: a cross sectional study

Abstract

BackgroundImmigrants from South Asia to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM). We explored pathogenic factors that might contribute to the high risk of T2DM in Pakistani immigrants to Norway.MethodsA cross-sectional study was performed in 18 Pakistani and 21 Norwegian men and women with T2DM (age 29 – 45 years), recruited from two hospital out-patient clinics. Anthropometrics and a two-step euglycemic, hyperinsulinemic clamp with measurements of non-esterified fatty acids (NEFA) during clamp, was performed in all patients. Insulin sensitivity, given as the Glucose Infusion Rate (GIR) and Insulin Sensitivity Index (ISI), was calculated from the two euglycemic clamp steps. Fasting adipokines and inflammatory mediators were measured. Continuous variables between groups were compared using Student’s t test or Mann–Whitney U test as appropriate. Spearman’s correlation coefficient and multiple linear regression analyses were used.ResultsDespite having a lower BMI, Pakistani patients were more insulin resistant than Norwegian patients, during both low and high insulin infusion rates, after adjustment for sex and % body fat: median (interquartile range) GIR(low insulin): 339.8(468.0) vs 468.4(587.3) μmol/m2/min (p = 0.060), ISI(low insulin): 57.1(74.1) vs 79.7(137.9) μmol/m2/min (p = 0.012), GIR(high insulin): 1661.1(672.3) vs 2055.6(907.0) μmol/m2/min (p = 0.042), ISI(high insulin): 14.2(7.3) vs 20.7(17.2) μmol/m2/min (p = 0.014). Pakistani patients had lower percentage NEFA suppression 30 minutes into clamp hyperinsulinemia than Norwegians: 41.9(90.6)% vs 71.2(42.1)%, (p = 0.042). The relationship of ISI to BMI, leptin and interleukin-1 receptor antagonist also differed between Norwegians and Pakistanis.ConclusionsCompared with Norwegian patients, Pakistani patients with T2DM had lower insulin sensitivity, affecting both glucose and lipid metabolism. The relation of insulin sensitivity to BMI and some adipokines also differed between the groups.

Living with Diabetes: Personal Interviews with Pakistani Women in Norway

“…For instance, in the early 2000s, the YY paradox was introduced after two researchers, Yudkin (European background) and Yajnik (Indian background), noticed that they both had a normal BMI value of 22 kg/m 2 , but remarkably different adiposities, 9% and 21%, respectively [32]. "The Asian Indian phenotype" was established, referring to the tendency of South Asians to have higher adiposity [82], lower skeletal muscle mass, and a higher degree of insulin resistance and pancreatic β-cell dysfunction [83,84] at any given BMI level than those of European descent [81,82,[85][86][87]. Even at normal BMI values (22 kg/m 2 ),…”

Fetuin-A mediates the difference in adipose tissue insulin resistance between young adult pakistani and norwegian patients with type 2 diabetes

“…DIPI is a cross-sectional study comparing young first generation Pakistani immigrants with T2DM living in Oslo, Norway to ethnic Norwegian patients aged ≤ 45 years [ 9 , 26 ]. Exclusion criteria were: ethnicities other than Norwegian or Pakistani, positive antibodies to glutamic acid decarboxylase (GAD) or islet antigen 2 (IA2) auto-antibodies, age > 45 years, persons unwilling or unable to give informed consent.…”

“…Details regarding the study participants had been described previously [ 9 , 26 ]. Briefly, T2DM patients of either Pakistani ( n = 18) or Norwegian ( n = 21) origin (51% women) between age 29 to 45 years were recruited from the diabetes outpatient clinics at Lovisenberg Deaconess Hospital and Aker University Hospital in Oslo.…”

“…The pathophysiology of T2DM in this population may differ from the common form of T2DM in the Western population, and a deeper understanding may help to develop more efficient prevention and treatment strategies, and also give new insight into the general pathogenesis of T2DM [ 8 ]. For example, our previous findings indicated a more pronounced influence of insulin resistance on lipid metabolism in Pakistani compared to Norwegian patients with T2DM [ 9 ].…”

“…Furthermore, fetuin-A may inhibit adiponectin production in adipocytes, contributing to insulin resistance [ 24 ]. However, it remains unknown if ethnic differences in adipose tissue insulin resistance [ 9 ] can be explained by altered secretion of fetuin-A.…”