LETTERSIn conclusion, sIL-2R concentrations interleukin 2-receptor secretion defect

in vitro in newly diagnosed type Iare increased in patients with IDDM, andLETTERSthis is not correlated with the metabolic diabetic patients. Diabetes 1989; 38:status. This is in accordance with some 310–315.

5. Zier KS, Leo MM, Spielman RS, Bakerearlier studies,1,2 while being contradic-tory with the report of Wagner et al. L. Decreased synthesis of interleukin-

2 (IL-2) in insulin-dependent diabeteswhich has shown the opposite.3 TheIncreased Soluble Interleukin-2 Receptor difference with this last study is difficult mellitus. Diabetes 1984; 33: 552–Concentrations in Patients with Insulin- to explain, but differences in genetic 555.dependent Diabetes Mellitus background of the patients or the method 6. Kaye WA, Adri MNS, Soeldner JS,

Rabinowe SL, Kaldany A, Kahn R, etof sIL-2R assay may be the cause. sIL-2Rconcentrations were higher in both ND- al. Acquired defect in interleukin-2The central pathogenetic event in insulin- and LS-IDDM patients when compared production in patients with type Idependent (Type 1) diabetes mellitus with controls, arguing for a continuous diabetes mellitus. N Engl J Med 1986;(IDDM) is the T-lymphocyte-mediated activation of the T-cells in Type I diabetes. 315: 920–924.destruction of insulin-producing b-cells. The increased in vivo cleavage of sIL- 7. Katz JD, Benoist C, Mathis D. TAntigenic stimulation of T-lymphocytes 2R from activated lymphocytes is very helper cell subsets in insulin-depen-results in both production of interleukin- probably the cause for the reported defec- dent diabetes. Science 1995; 268:2 (IL-2) and expression of IL-2 receptors tive in vitro production of sIL-2R by cells 1185–1188.(IL-2R). During the activation of T-lympho- of IDDM patients.4 The higher concen- 8. Heath HR, Allison J, Hoffmann MW,cytes, a 42-kD fragment of IL-2R is cleaved trations of sIL-2R (by shedding from IL- Schonrich G, Hammerling G, Arnoldoff and circulates as a soluble marker of 2-responsive T lymphocytes) in IDDM B, Miller JFAP. Autoimmune diabeteslymphocyte activation (sIL-2R). Several patients may represent an argument for as a consequence of locally producedstudies have investigated the presence of the importance of IL-2 in the pathogenesis interleukin-2. Nature 1992; 359:sIL-2R in IDDM patients, with conflicting of Type 1 diabetes. Although several 547–549.results. While some studies reported studies have shown that IL-2 productionincreased concentrations,1,2 other investi- is impaired in IDDM patients,5,6 this mightgators have found lower levels of circulat- not represent the real situation at theing sIL-2R in IDDM patients when com- tissue level. Thus, it has been recentlypared with normal volunteers.3 The aim shown that the Th1 lymphocyte subsetof our study was to assess the sIL-2R We Require a British Prevention of Dia-(producing high levels of IL-2 and IFN-concentrations in newly diagnosed IDDM betes Complications Trialgamma) actively promote diabetes in(ND-IDDM) and long-standing IDDM (LS- neonatal NOD mice,7 while autoimmuneIDDM) patients, and compare them with Diabetes results in increased risk of heart,diabetes develops in transgenic micesIL-2R levels in healthy controls. renal, ophthalmic, cerebrovascular dis-expressing IL-2 and class I molecule H-Thirteen ND-IDDM patients (7 men ease and neuropathy with peripheral vas-2Kb in their b-cells.8and 6 women; mean age 22 (13–23) cular disease. It is conceivable that a

years), and 14 LS-IDDM patients (8 men large proportion—perhaps some 80 %—Mihai G. Neteaa, Nicolae Hancuand 7 women; mean age 28 (12–37) of the associated morbidity and financialDiabetes Center and Clinicyears) were investigated. The ND-IDDM cost is avoidable by decreasing the rateStr. Clinicilor nr. 2,patients were investigated within 10 days of complications seen in people with3400 Cluj-Napoca, Romaniaof diagnosis, after the metabolic state was diabetes to that of the non-diabetic popu-

stabilized. The duration of diabetes in the lation. This is possible because peopleLS-IDDM group was longer than 1 year. with diabetes are more than four timesSerum fasting C-peptide levels were below as likely to be admitted to hospital, and0.1 nmol l−1 in all patients. Sixteen healthy they stay on average almost twice as longReferencesvolunteers (9 men, 7 women, mean age as people who do not have diabetes.123 (19–28) years) represented the control There is evidence from the Diabetesgroup. Serum sIL-2R concentrations were 1. Giordano C, Galuzzo A, Marco A, Control and Complications Trial thatdetermined using a two-site enzyme Panto F, Amato MP, Caruso C, Bompi- microvascular disease complication-ratesimmunoassay (Boehringer-Mannheim, ani GD. Increased soluble interleukin- can be reduced in Type 1 diabetes.2Germany); detection limit was 2 receptor levels in the sera of type However, strictly speaking, the financial20 pmol l−1. Values are given as mean I diabetic patients. Diabetes Res 1988; cost of Type 1 diabetes is less important± standard deviation. Differences were 8: 135–138. than Type 2 diabetes which strikes at acompared using Kruskall-Wallis test and 2. Burke GW, Cirocco R, Markou M, ratio of some 3 : 1 people, and in olderconsidered significant at p , 0.05. Agramonte RF, Rabinovitch A, Miller age groups.

The sIL-2R concentrations were signifi- J, Skyler JS. Effect of cyclosporin A A forthcoming Kings Fund report willcantly higher in IDDM patients when on serum tumor necrosis alpha in publish an estimate of the annual hospitalcompared with healthy controls new-onset type I (insulin-dependent) expenditure for diabetes at some 8 % of(120.4 ± 61.4 vs 81.9 ± 26.2 pmol l−1, diabetes mellitus. J Diabetes Compli- NHS expenditure, or roughly £2 billion.3p = 0.0188). The sIL-2R concentrations cations 1994; 8: 40–44. This disguises the less tangible costs ofwere increased in both ND-IDDM and 3. Wagner R, Bonifacio E, Bingley PJ, disease morbidity in terms of reducedLS-IDDM patients when compared with Genovese S, Reinwein D, Botazzo quality of life, psychological ill-health,controls, but no significant difference GF. Low interleukin-2 receptor levels and decreased working productivity.could be found between the two groups in serum of patients with insulin- Studying a disease with the complexityof patients (112.6 ± 56.5 vs dependent diabetes. Clin Invest 1994; of diabetes involves many unusual prob-127.7 ± 66.9 pmol l−1, p = 0.5121). No 72: 494–498. lems. For example, onset is usually insidi-correlation between sIL-2R and the meta- 4. Giordano C, Panto F, Caruso C, ous, the wide variety of vascular compli-bolic status (glycemia and glycated Modica MA, Zambito AM, Sapienza cations may only manifest themselves

after a number of years in a state ofhaemoglobin) could be found. M, et al. Interleukin 2 and soluble

168 CCC 0742–3071/97/020168–03 1997 by John Wiley & Sons, Ltd. DIABETIC MEDICINE, 1997; 14: 168–170