Insulin treatment in IA-2A-positive relatives of type 1 diabetic patients.
OBJECTIVE
We examined whether parenteral regular insulin can prevent diabetes in IA-2 antibody-positive (IA-2A+) relatives of type 1 diabetic patients, using a trial protocol that differed substantially from that of the Diabetes Prevention Trial-1.


METHODS
Twenty-five IA-2A+ relatives received regular human insulin twice a day for 36 months, during which time they were followed (median [interquartile range; IQR]: 47 [19-66] months) for glucose tolerance, HbA(1c) and islet autoantibodies, together with 25 IA-2A+ relatives (observation/control group) who fulfilled the same inclusion criteria, but were observed for 52 [27-67] months (P=0.58).


RESULTS
Twelve (48%) insulin-treated relatives and 15 (60%) relatives in the control group developed diabetes. There was no difference in diabetes-free survival between the two groups (P=0.97). Five-year progression (95% confidence interval) was 44% (25-69) in the insulin-treated group and 49% (29-70) in the observation group. At inclusion, progressors tended to have a higher pro-insulin/C-peptide ratio than non-progressors when measured 2 hours after a standardized glucose load (median [IQR]: 2.7% [1.8-4.3] vs. 1.6% [1.1-2.1]; P=0.01). No major hypoglycaemic episodes or significant increases in body mass index or diabetes autoantibodies were observed.


CONCLUSIONS
Prophylactic injections of regular human insulin were well tolerated, but failed to prevent type 1 diabetes onset in IA-2A+ relatives.
Vandemeulebroucke
E
E
Diabetes Research Centre, Brussels Free University, Belgium.
Gorus
F K
FK
Decochez
K
K
Weets
I
I
Keymeulen
B
B
De Block
C
C
Tits
J
J
Pipeleers
D G
DG
Mathieu
C
C
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001530:Belgium; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002648:Child; D016001:Confidence Intervals; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018149:Glucose Intolerance / Q000517:prevention & control; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000175:diagnosis; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010375:Pedigree; D011384:Proinsulin / Q000097:blood; D013997:Time Factors; D055815:Young Adult
D001323:Autoantibodies; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; D011384:Proinsulin; C096322:ICA512 autoantibody