Differences in Inflammatory Pathways Between Dutch South Asians vs Dutch Europids With Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism, vol. 108, pp. 931–940

Abstract

CONTEXT: South Asian individuals are more prone to develop type 2 diabetes (T2D) coinciding with earlier complications than Europids. While inflammation plays a central role in the development and progression of T2D, this factor is still underexplored in South Asians. OBJECTIVE: This work aimed to study whether circulating messenger RNA (mRNA) transcripts of immune genes are different between South Asian compared with Europid patients with T2D. METHODS: A secondary analysis was conducted of 2 randomized controlled trials of Dutch South Asian (n = 45; age: 55 ± 10 years, body mass index [BMI]: 29 ± 4 kg/m2) and Dutch Europid (n = 44; age: 60 ± 7 years, BMI: 32 ± 4 kg/m2) patients with T2D. Main outcome measures included mRNA transcripts of 182 immune genes (microfluidic quantitative polymerase chain reaction; Fluidigm Inc) in fasted whole-blood, ingenuity pathway analyses (Qiagen). RESULTS: South Asians, compared to Europids, had higher mRNA levels of B-cell markers (CD19, CD79A, CD79B, CR2, CXCR5, IGHD, MS4A1, PAX5; all fold change > 1.3, false discovery rate [FDR] < 0.008) and interferon (IFN)-signaling genes (CD274, GBP1, GBP2, GBP5, FCGR1A/B/CP, IFI16, IFIT3, IFITM1, IFITM3, TAP1; all FC > 1.2, FDR < 0.05). In South Asians, the IFN signaling pathway was the top canonical pathway (z score 2.6; P < .001) and this was accompanied by higher plasma IFN-γ levels (FC = 1.5, FDR = 0.01). Notably, the ethnic difference in gene expression was larger for women (20/182 [11%]) than men (2/182 [1%]). CONCLUSION: South Asian patients with T2D show a more activated IFN-signaling pathway compared to Europid patients with T2D, which is more pronounced in women than men. We speculate that a more activated IFN-signaling pathway may contribute to the more rapid progression of T2D in South Asian compared with Europid individuals.

Authors 13

1. Maaike E. Straat corresponding Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

2. Borja Martínez‐Téllez Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

3. Huub J. van Eyk Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

4. Maurice B. Bizino Aachen Department of Radiology, Leiden University Medical Center Division of Endocrinology Department of Medicine, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

   Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

5. Suzanne van Veen Aachen Department of Infectious Diseases

   Leiden University Medical Center

   Affiliation as printed

   Department of Infectious Diseases, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

6. Eleonora Vianello Aachen Department of Infectious Diseases

   Leiden University Medical Center

   Affiliation as printed

   Department of Infectious Diseases, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

7. Rinke Stienstra

   Radboud University Nijmegen · Radboud University Medical Center · Wageningen University & Research

   Affiliation as printed

   Department of Medicine, Radboud University Medical Center , 6525 XZ Nijmegen , the Netherlands

   Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University , 6708 PB Wageningen , the Netherlands

8. Tom H. M. Ottenhoff Aachen Department of Infectious Diseases

   Leiden University Medical Center

   Affiliation as printed

   Department of Infectious Diseases, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

9. Hildo J. Lamb Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

10. Johannes W. A. Smit

    Radboud University Nijmegen · Radboud University Medical Center

    Affiliation as printed

    Department of Medicine, Radboud University Medical Center , 6525 XZ Nijmegen , the Netherlands

11. Ingrid M. Jazet Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

    Leiden University Medical Center

    Affiliation as printed

    Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

12. Patrick C.N. Rensen Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

    Leiden University Medical Center

    Affiliation as printed

    Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

13. Mariëtte R. Boon Aachen Division of Endocrinology Department of Medicine, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

    Leiden University Medical Center

    Affiliation as printed

    Division of Endocrinology, Department of Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands

    Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , 2333 ZA Leiden , the Netherlands