Tissue polypeptide–specific antigen (TPS) is a marker of proliferation activity (1,2,3). Because diabetes is characterized by proliferative lesions in various organs, we hypothesized that serum TPS concentrations might be elevated in young patients with type 1 diabetes. Thus, for the first time, serum TPS concentrations in young patients with type 1 diabetes were determined and compared with those of age-matched healthy control subjects. Furthermore, their relation to age, sex, BMI, Tanner stage, insulin requirements, existence of complications, and duration and metabolic control of the disease, as expressed by HbA1c, were investigated. This study was approved by the institutional ethics committee, and informed consent was obtained.

We investigated 97 subjects, 60 with type 1 diabetes (29 male and 31 female subjects) and 37 healthy control subjects (18 male and 19 female subjects). Those with type 1 diabetes were recruited consecutively during the study period (January 2000 to December 2000) from the patients attending our Diabetes Center. Control subjects were healthy siblings and young students. The subjects’ characteristics appear in Table 1. Pubertal status, assessed through Tanner staging, was in accordance with age in both groups. Five type 1 diabetes patients presented complications (microalbuminuria, overt proteinuria, or retinopathy).

Fasting serum TPS concentrations were measured by a sequential chemiluminescent enzyme-labeled immunometric assay and were found to be significantly higher (means ± SD) in type 1 diabetes patients compared with healthy control subjects (54.38 ± 33.27 vs. 29.03 ± 13.10 units/l [95% CI 15.8–34.9]; P < 0.0005), even when excluding patients with complications from the analysis (53.12 ± 32.80 vs. 29.03 ± 13.10 units/l; P < 0.0005). Serum TPS concentrations were significantly correlated with HbA1c (r = 0.26; P = 0.042). A significant correlation was also found in a multiple regression model between serum TPS concentrations and HbA1c (P = 0.047; adjusted R2 = 0.05; B = 4.5; SE[B] = 2.2; CI 95% 0.06–8.9) when HbA1c, age, and BMI were introduced as independent variables. No other correlation existed between serum TPS concentrations and age, sex, BMI, Tanner stage, disease duration, insulin requirements, or the presence of complications with bivariate linear regression analysis. Also, no significant difference existed in serum TPS concentrations at different categories of HbA1c, age, disease duration, and insulin requirements.

The results of this study indicate that serum TPS concentrations are elevated in young patients with type 1 diabetes compared with healthy control subjects and depend significantly on the metabolic control of the disease.

Rebhandl et al. (4) found that serum TPS concentrations in healthy subjects aged 8–18 years do not differ from those in adults, and no significant differences exist between male and female subjects, findings confirmed in this study also for type 1 diabetes patients. Furthermore, serum TPS concentrations do not seem to depend on the duration of the disease, but rather on its metabolic control, although the latter accounts for only 5% of TPS variance among individuals in our study.

In conclusion, the high serum TPS concentrations in young patients with type 1 diabetes—even before disease complications are evident—and the significant correlation with the metabolic control of the disease argue for further studies that include greater numbers of individuals presenting complications of type 1 diabetes in order to elucidate the underlying mechanisms and evaluate whether serum TPS concentrations could serve as a reliable marker for disease progression.

Table 1—

Demographic data and biochemical findings in participating subjects with type 1 diabetes and healthy control subjects

Type 1 diabetic subjectsControl subjectsP
Age (years) 15.31 ± 5.22 (5–23.7) 13.55 ± 5.89 (4–22.8) NS 
BMI (kg/m220.68 ± 3.38 (13.7–28.7) 19.56 ± 4.06 (13.2–24.3) NS 
Tanner stage    
 1 12 14  
 2  
 3  
 4  
 5 32 11  
HbA1c (%) 8.83 ± 1.85 (6.10–14.0) —  
Insulin requirements (units · kg–1 · day–10.89 ± 0.27 (0.36–1.80) —  
Disease duration (years) 5.31 (0.01–17.58) —  
Type 1 diabetic subjectsControl subjectsP
Age (years) 15.31 ± 5.22 (5–23.7) 13.55 ± 5.89 (4–22.8) NS 
BMI (kg/m220.68 ± 3.38 (13.7–28.7) 19.56 ± 4.06 (13.2–24.3) NS 
Tanner stage    
 1 12 14  
 2  
 3  
 4  
 5 32 11  
HbA1c (%) 8.83 ± 1.85 (6.10–14.0) —  
Insulin requirements (units · kg–1 · day–10.89 ± 0.27 (0.36–1.80) —  
Disease duration (years) 5.31 (0.01–17.58) —  

Data are means ± SD (range), n, and median (range).

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Address correspondence to A. Malamitsi-Puchner, MD, Second Department of Obstetrics and Gynecology, University of Athens, Soultani 19, GR-10682 Athens, Greece. E-mail: geocre@aretaieio.uoa.gr.