Aims: To elucidate the effect of prophylactic insulin, in a treatment schedule previously demonstrated to achieve beta-cell rest, in a group of high-risk, non-diabetic first-degree relatives of Type 1 diabetic patients.
Methods: Ten high risk subjects for Type 1 diabetes mellitus (DM) (seven male/three female, aged 19.8+/-9.6 years) defined as: first-degree relatives of Type 1 DM patients, islet cell autoantibodies (ICA) > or =20 Juvenile Diabetes Foundation (JDF) units twice, first phase insulin response (FPIR) to glucose in an intravenous glucose tolerance test < or =10th percentile of a control group were included in an open pilot trial. Five were treated with subcutaneous insulin: 0.1 IU/kg body weight/day of neutral protamine hagedorn (NPH) insulin once a day. Five declined treatment and were used as controls. Control and treatment groups did not differ in terms of age, ICA, insulin autoantibodies (IAA), glutamic acid dehydrogenase (GAD) and FPIR.
Results: Three out of five subjects in both groups developed Type 1 DM during follow-up: after 21, and 32-57 months in the insulin-treated group and after 4, and 18-60 months in the untreated group. Three out of six subjects who developed overt diabetes had a FPIR below the 2nd percentile of the control value at the onset of the study. All subjects who developed diabetes were positive for antibodies to GAD and expressed the HLA-DR3 or DR4 alleles, whereas only one of the non-progressors had these parameters (P < 0.05). During follow-up, a decrease in ICA titres was observed in the group which received prophylactic insulin in contrast with the untreated group. GAD, as well as insulin secretory capacity, remained unchanged in both groups.
Conclusion: The subcutaneous administration of insulin (0.1 IU/kg body weight/day of NPH insulin once a day) in our group of high-risk subjects for Type 1 DM produced only a minor effect in some immunological markers (ICA), without preventing the development of overt disease. The efficacy and safety of insulin used at either a different dose or by a different route, as well as its potential effect in the early phases of prediabetes, warrants further investigation.