[CITATION][C] Plasma concentrations of macrophage migration inhibitory factor are elevated in Pima Indians compared to Caucasians and are associated with insulin …

B Vozarova, C Metz, N Stefan, R Hanson, R Lindsay… - Diabetologia, 2002 - Springer
B Vozarova, C Metz, N Stefan, R Hanson, R Lindsay, R Bucala, C Bogardus, P Tataranni
Diabetologia, 2002Springer
concentrations, and acute insulin response (AIR 25-g intravenous glucose tolerance test)
between Pima Indians and Caucasians (data not shown). Insulin action (M,
hyperinsulinaemic euglycaemic clamp [7]) was lower in Pima Indians compared to
Caucasians (3.75±1.18 and 4.72±1.79 mg· kgEMBS–1· min–1, respectively, p< 0.05). While
in these healthy subjects, MIF was frequently below the detection level of the assay, the
frequency distribution of MIF in Pima Indians was different from Caucasians (Fig. 1A) with …
concentrations, and acute insulin response (AIR 25-g intravenous glucose tolerance test) between Pima Indians and Caucasians (data not shown). Insulin action (M, hyperinsulinaemic euglycaemic clamp [7]) was lower in Pima Indians compared to Caucasians (3.75±1.18 and 4.72±1.79 mg· kgEMBS–1· min–1, respectively, p< 0.05). While in these healthy subjects, MIF was frequently below the detection level of the assay, the frequency distribution of MIF in Pima Indians was different from Caucasians (Fig. 1A) with higher fasting MIF concentrations in Pima Indians (Wilcoxon Rank sum test p= 0.04). Thus fasting MIF concentrations were higher than 5 ng/ml in 39% of Pima Indians, but not in any of the Caucasians. Fasting MIF was below the level of detection of the assay in 71% of Caucasians, 54% of Pima Indians (Fig. 1A). MIF concentrations at 2-h tended to be higher in Pima Indians compared to Caucasians (Wilcoxon Rank sum test p= 0.1). There was no difference between fasting and 2-h MIF concentrations (p= 0.2). Fasting MIF concentrations were negatively associated with M before (Fig. 1B) and after adjustment for age, sex and percentage of body fat (r=–0.80, p= 0.0001). Moreover, those subjects who had undetectable fasting MIF concentrations had on average higher M values compared to those who had detectable fasting MIF concentrations (4.7±1.5 and 3.1±0.7 mg· kgEMBS–1· min–1, respectively, p= 0.0005). 2-h MIF concentrations were not correlated with M (r=–0.06, p= 0.9). There was no correlation between fasting or 2-h MIF and measures of adiposity (body fat and BMI), fasting and 2-h glucose and insulin and AIR before or after adjustment for age and sex (all p> 0.05). Another study [4] showed that serum MIF concentrations were higher in patients with Type II diabetes compared to their age and sex matched normal healthy control subjects. We extend this observation by showing higher MIF concentrations in non-diabetic Pima Indians, a population at high risk for the development of Type II diabetes, compared to non-diabetic Caucasians. A study carried out in isolated rat islets showed that MIF production is regulated by glucose [3]. Despite this, we show that MIF concentrations are not associated with fasting glucose, a finding in agreement with a previous study [4], and additionally find no association between serum concentrations of MIF and 2 h plasma glucose. MIF has also been proposed to act in a paracrine fashion to modulate insulin secretion. Thus, in vitro immunoneutralization of MIF was shown to reduce insulin secretion [3]. However, we show that MIF concentrations are not associated with fasting or 2-h insulin and acute insulin secretory response. By contrast, we show that fasting MIF concentrations are strongly associated with insulin resistance in vivo. Associations of insulin resistance and MIF in healthy human subjects have not been reported, although MIF is released
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