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Relationship of betatrophin with youth onset type 2 diabetes among Asian Indians

  • Kuppan Gokulakrishnan
    Correspondence
    Corresponding author at: Department of Research Biochemistry, Madras Diabetes Research Foundation 4, Conran Smith Road, Gopalapuram, Chennai 600 086, India. Tel.: +91 44 4396 8888; fax: +91 44 2835 0935.
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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  • Kalaivani Manokaran
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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  • Gautam Kumar Pandey
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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  • Anandakumar Amutha
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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  • Harish Ranjani
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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  • Ranjit Mohan Anjana
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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  • Viswanathan Mohan
    Affiliations
    Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control, IDF Centre for Education, Gopalapuram, Chennai 600086, India
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      Highlights

      • We studied betatrophin levels and their association with youth-onset T2DM individuals.
      • Betatrophin levels were significantly lower in T2DM-Y compared to NGT group.
      • Betatrophin is negatively correlated with insulin resistance and fasting glucose.
      • Betatrophin shows a positive correlation with the oral disposition index.
      • Betatrophin was associated with T2DM-Y but lost significance when adjusted for HOMAIR.

      Abstract

      Background and Aims

      Betatrophin is emerging as a marker for compensatory beta cell proliferation. While betatrophin has been mainly investigated in adults, there is a lack of data on betatrophin levels in youth-onset type 2 diabetes mellitus (T2DM-Y). The aim of this study was to determine levels of betatrophin and its association with T2DM-Y in Asian Indian participants.

      Methods

      We recruited 100 individuals with normal glucose tolerance (NGT; n = 50) and newly-diagnosed cases (within 18 months of first diagnosis) of T2DM-Y (n = 50) with onset between 12 and 24 years of age from a large tertiary diabetes center in Chennai in southern India. Insulin resistance was measured by homeostatic model (HOMA-IR) and insulin secretion by oral disposition index (DIO). Betatrophin levels were measured by enzyme-linked immunosorbent assay.

      Results

      Betatrophin levels were significantly lower in the T2DM-Y group compared with the NGT group (803 vs 1104 pg/ml, p < 0.001). Betatrophin showed a significant inverse correlation with waist circumference (p = 0.035), HOMA-IR (p < 0.001), fasting and 2 h postprandial glucose (p < 0.01), glycated hemoglobin (p = 0.019) and a positive correlation with fasting C-peptide (p < 0.001) and DIO (p = 0.012). In regression analysis, betatrophin was independently associated with T2DM-Y even after adjustment for age, gender, and waist circumference (OR per standard deviation: 0.562, 95% CI: 0.342–0.899, p = 0.019). However, the association was lost when HOMA-IR was included in the model (OR: 1.141, 95% CI: 0.574–2.249; p = 0.646).

      Conclusion

      Betatrophin levels are lower in T2DM-Y and this association is likely mediated through insulin resistance.

      Abbreviations:

      T2DM-Y (youth-onset type 2 diabetes mellitus), NGT (normal glucose tolerance), DIO (oral disposition index), GAD (glutamic acid decarboxylase), WHO (World Health Organization)

      Keywords

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