LONGITUDINAL-STUDY OF FASTING PROINSULIN IN 148 SIBLINGS OF PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Objective: To follow proinsulin immunoreactive material (PIM) in healt hy siblings from the time of diagnosis of insulin-dependent diabetes m ellitus (IDDM) in the proband, for at least 2 years. Design and method s: The study comprised 148 siblings representing 112 families, The sib lings were recruited from the nationwide 'Childhood Diabetes in Finlan d' study and tested for immunological markers. If a sibling was found positive for islet cell antibodies (ICA) or insulin autoantibodies (IA A), PLM sampling was extended beyond 2 years. Results: Of the 148 sibl ings, 12 developed IDDM 3-53 months after the diagnosis in the proband , Eleven of these siblings exhibited initially normal PIM concentratio ns. In nine siblings, samples were available both more than 6 months a nd during the last 6 months before the diagnosis of IDDM; PIM concentr ations increased in seven, remained unchanged in one, and decreased in one in the period up to the diagnosis of IDDM (P < 0.05). Median PIM concentration did not change significantly during the examination peri od of 2 years in the 136 siblings who did not contract IDDM. Constantl y increased PIM concentrations were found in 12 of the 136 siblings wh o did not develop IDDM, These 12 siblings were all ICA negative, Concl usion: In healthy siblings of IDDM patients exhibiting an initially lo w PIM concentration, an abrupt increase in PIM seems to precede the cl inical manifestation of IDDM within 0-6 months. However, there were to o few patients available to close follow-up to allow calculation of an y predictive value of this increase. Persistently increased PRM concen trations were present in some healthy siblings who did not develop IDD M. The reason for that finding remains unclear, but it could be associ ated with previous B cell damage.