Pancreatic Fat Content and β-Cell Function in Men With and Without Type 2 Diabetes

  1. Maarten E. Tushuizen, MD1,
  2. Mathijs C. Bunck, MD1,
  3. Petra J. Pouwels, PHD2,
  4. Saskia Bontemps, MSC1,
  5. Jan Hein T. van Waesberghe, MD, PHD3,
  6. Roger K. Schindhelm, MD, PHD1,
  7. Andrea Mari, PHD4,
  8. Robert J. Heine, MD, PHD, FRCP1 and
  9. Michaela Diamant, MD, PHD1
  1. 1Department of Endocrinology/Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands
  2. 2Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, the Netherlands
  3. 3Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands
  4. 4Institute of Biomedical Engineering, National Research Council, Padova, Italy
  1. Address correspondence and reprint requests to M. Diamant, MD, PhD, Endocrinology/Diabetes Center, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. E-mail: m.diamant{at}vumc.nl

Abstract

OBJECTIVE—Insulin resistance, associated with increased lipolysis, results in a high exposure of nonadipose tissue to lipids. Experimental data indicate that fatty infiltration of pancreatic islets may also contribute to β-cell dysfunction, but whether this occurs in humans in vivo is unknown.

RESEARCH DESIGN AND METHODS—Using proton magnetic resonance spectroscopy and oral glucose tolerance tests, we studied the association of pancreatic lipid accumulation in vivo and various aspects of β-cell function in 12 insulin-naive type 2 diabetic and 24 age- and BMI-matched nondiabetic men.

RESULTS—Patients versus control subjects had higher A1C, fasting plasma glucose, and insulin and triglyceride levels and lower HDL cholesterol, but similar waist circumference. Median (interquartile range) pancreatic fat content in patients and control subjects was 20.4% (13.4–43.6) and 9.7% (7.0–20.2), respectively (P = 0.032). Pancreatic fat correlated negatively with β-cell function parameters, including the insulinogenic index adjusted for insulin resistance, early glucose-stimulated insulin secretion, β-cell glucose sensitivity, and rate sensitivity (all P < 0.05), but not potentiation. However, these associations were significantly affected by the diabetic state, such that a significant association of pancreatic fat with β-cell dysfunction was only present in the nondiabetic group (all P < 0.01), suggesting that once diabetes occurs, factors additional to pancreatic fat account for further β-cell function decline. In control subjects, the association of pancreatic fat and β-cell function remained significant after correction for BMI, fasting plasma glucose, and triglycerides (P = 0.006).

CONCLUSIONS—These findings indicate that pancreatic lipid content may contribute to β-cell dysfunction and possibly to the subsequent development of type 2 diabetes in susceptible humans.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 31 July 2007. DOI: 10.2337/dc07-0326.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0326.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted July 25, 2007.
    • Received February 15, 2007.
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  1. Diabetes Care vol. 30 no. 11 2916-2921
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