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Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

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Abstract

Aims/hypothesis

Early-onset type 2 diabetes is associated with marked visceral obesity and extreme insulin resistance, but its pathogenesis and response to treatment are not completely understood. We studied physical fitness, whole-body and hepatic glucose turnover, and insulin secretion in young obese Irish subjects before and after 3 months of aerobic exercise training. We hypothesised that exercise alone, with stable diet, should improve insulin sensitivity.

Materials and methods

Anthropometric parameters and maximum volume of oxygen utilisation (VO2max) were measured in 13 subjects with type 2 diabetes and 18 non-diabetic control subjects, matched for age and BMI. Insulin sensitivity and hepatic glucose turnover were measured using the hyperinsulinaemic–euglycaemic clamp. Insulin secretion was assessed from an OGTT and a modified intravenous glucose tolerance test. Some subjects (seven type 2 diabetic, 14 non-diabetic control subjects) then completed a 12-week supervised aerobic exercise programme. All measurements were repeated on completion of the exercise programme.

Results

Type 2 diabetic subjects had higher WHR, systolic blood pressure and triacylglycerols than non-diabetic control subjects. They were significantly more insulin-resistant as measured both by the clamp and oral glucose insulin sensitivity. They also displayed marked defects in insulin secretion in response to oral and intravenous glucose challenges. Exercise intervention had no significant effect on whole-body or hepatic insulin sensitivity or insulin secretion. VO2max increased significantly in the non-diabetic control subjects, but not in the type 2 diabetic subjects after exercise training.

Conclusions/interpretation

Young obese subjects with type 2 diabetes are severely insulin-resistant with marked loss of beta cell function compared with control subjects matched for age and obesity. Neither group responded metabolically to aerobic exercise intervention.

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Abbreviations

GLUT4:

glucose transporter 4

IVGTT:

intravenous glucose tolerance test

OGIS:

oral glucose insulin sensitivity

VO2max:

maximum volume of oxygen utilisation

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Acknowledgements

This study was funded by the Diabetes Education and Research Fund and in part by unrestricted educational grants from Pfizer and Novo Nordisk. The authors are especially grateful to the study participants.

Duality of interest

None of the authors have any duality of interest to declare.

Author information

Authors and Affiliations

  1. Metabolic Research Unit, Department of Endocrinology, Hospital 5, St James’ Hospital, Trinity College Dublin, Dublin 8, Ireland

    N. Burns, F. M. Finucane, M. Hatunic, M. Gilman, M. Murphy & J. J. Nolan

  2. Department of Chemical Pathology, St James’ Hospital, Dublin, Ireland

    D. Gasparro

  3. Institute of Biomedical Engineering, National Research Council, Padua, Italy

    A. Mari

  4. CNR Institute, Pisa, Italy

    A. Gastaldelli

Authors
  1. N. Burns
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  2. F. M. Finucane
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  3. M. Hatunic
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  4. M. Gilman
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  5. M. Murphy
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  6. D. Gasparro
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  7. A. Mari
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  8. A. Gastaldelli
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  9. J. J. Nolan
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Corresponding author

Correspondence to J. J. Nolan.

Additional information

N. Burns and F. M. Finucane contributed equally to this work.

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Burns, N., Finucane, F.M., Hatunic, M. et al. Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training. Diabetologia 50, 1500–1508 (2007). https://doi.org/10.1007/s00125-007-0655-7

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  • DOI: https://doi.org/10.1007/s00125-007-0655-7

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