High-sensitivity C-reactive protein (hsCRP) was shown in large epidemiological studies to predict the risk of cardiovascular disease in apparently healthy individuals (1). In this presentation Dr. Pfutzner presents data from the IRIS-II study showing that hsCRP may also be a good marker of macrovascular risk in type 2 diabetic patients.

In the state of pathologically increased demand on the beta cells, intact proinsulin appears in the plasma along with insulin and C-peptide due to the inability of enzymes to cleave excess proinsulin. A chemiluminescence assay that can measure intact proinsulin has recently been made available, and has started to be used for research purposes. Using this assay it was demonstrated from a study of 48 diabetic patients that intact proinsulin is a highly specific indicator of insulin resistance (2). Pfutzner and colleagues have also recently proposed the staging of type 2 diabetes according to beta-cell dysfunction (3), taking into account the secreted insulin and proinsulin levels.

This proposed staging model was applied in the IRIS-II, a cross-sectional study conducted in over 4000 German non-insulin-treated type 2 diabetic patients having a mean disease duration of about 5 years. The study aimed to identify diagnostic parameters for insulin resistance that could potentially be used in clinical practice, and confirmed that fasting intact proinsulin is a marker of insulin resistance. It was also found that the prevalence of macrovascular complications was highest in patients with the highest hsCRP levels and later stage beta-cell dysfunction and insulin resistance, although hsCRP levels were in the high risk range for all stages of beta-cell dysfunction and insulin resistance(4). Data from this study is preliminary and does not reflect current practice. Likewise, the proposed staging model is not currently used in clinical practice.

Copyright © 2004 E-MedHosting.com Inc.

After viewing this presentation the participant will be able to discuss:

- Evidence for intact proinsulin as a marker of insulin resistance
- The pathophysiological staging of type 2 diabetes based on beta-cell secretion
- Data from the IRIS-II study on the prevalence of macrovascular disease in type 2 diabetics in relation to hsCRP levels and stage of beta-cell dysfunction and insulin resistance.

1. Paul M. Ridker, M.D., Nader Rifai, Ph.D., Lynda Rose, M.S., Julie E. Buring, Sc.D., and Nancy R. Cook, Sc.D.Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular EventsNEJM.2002;347:1557-1565.

2. Andreas Pfützner, MD, PHD, Thomas Kunt, MD, Cloth Hohberg, MD, Agnes Mondok, MD, Sabine Pahler, MSC, Thomas Konrad, MD, Georg Lübben, MD and Thomas Forst, MD.Fasting Intact Proinsulin Is a Highly Specific Predictor of Insulin Resistance in Type 2 Diabetes Diabetes Care.2004;27:682-687.

3. Andreas Pfützner ; Anke H. Pfützner ; Martin Larbig ; Thomas Forst.Role of Intact Proinsulin in Diagnosis and Treatment of Type 2 Diabetes MellitusDiabetes Technology & Therapeutics.2004;6(3):405-412.

4. T. Forst, E. Standl, C. Hohberg, T. Konrad, J. Schulze, H. J. Strotmann, G. Lübben, S. Pahler, A. Bachinger, M. Langenfeld and A. Pfützner.IRIS II study: the IRIS II scoreassessment of a new clinical algorithm for the classification of insulin resistance in patients with Type 2 diabetesDiabetic Medicine.2004;21(10):1149.