Document Type


Publication Date



Statler College of Engineering and Mining Resources


Chemical and Biomedical Engineering



Type 1 diabetes mellitus is characterized by an inability to produce insulin endogenously. Based on a series of histopathology studies of patients with recent onset of the disease, it is commonly stated that the onset of clinical symptoms corresponds to an 80-95% reduction in beta cell mass. Motivated by the clinical importance of the degree of beta cell destruction at onset, a meta-analysis was used to determine the validity of this common wisdom.

Methods and Findings

The histopathology results identifying insulin containing islets in patients younger than 20 years of age were extracted from three different studies. The results for 105 patients were stratified by duration of diabetic symptoms and age at onset. Linear regression and a non-parametric bootstrap approach were used to determine the dependence of residual beta cell mass to age at onset. The percentage reduction in beta cell mass was highly correlated (p<0.001) with the age of onset with the greatest reduction in beta cell mass in the youngest patients. As this trend had not been previously observed, an alternative physiology-based model is proposed that captures this age-dependence.


The severity in beta cell reduction at onset decreased with age where, on average, a 40% reduction in beta cell mass was sufficient to precipitate clinical symptoms at 20 years of age. The observed trend was consistent with a physiology-based model where the threshold for onset is based upon a dynamic balance between insulin-production capacity, which is proportional to beta cell mass, and insulin demand, which is proportional to body weight.

Source Citation

Klinke DJ II (2008) Extent of Beta Cell Destruction Is Important but Insufficient to Predict the Onset of Type 1 Diabetes Mellitus. PLoS ONE 3(1): e1374.


© 2008 David Klinke II. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



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