I. Vauhkonen et al., Impaired insulin secretion in non-diabetic offspring of probands with latent autoimmnne diabetes mellitus in adults, DIABETOLOG, 43(1), 2000, pp. 69-78
Aims/hypothesis. This study was undertaken to investigate metabolic and gen
etic characteristics of latent autoimmune diabetes in adults (LADA).
Methods. We evaluated insulin secretory capacity with oral and intravenous
glucose tolerance tests (early insulin response) and hyperglycaemic clamp (
insulin secretory capacity) and the rates of whole body glucose uptake with
the euglycaemic clamp, HLA-DQB1 genotypes (time-resolved fluorescence) and
islet cell antibodies (ICA) (immunofluoresence) and antibodies to glutamic
acid decarboxylase (GAD) (radio-immunoprecipitation) in 36 non-diabetic of
fspring (LADA-offspring) of patients with Type II (non-insulin-dependent) d
iabetes mellitus who tested positive for ICA and/or GAD antibodies during t
he 10-year follow-up from the diagnosis and in 19 healthy control subjects
without a family history of diabetes.
Results. The early insulin response during the first 10 min of an intraveno
us glucose tolerance test was about 40% lower in the LADA-offspring than in
the control group (p = 0.008). Insulin secretory capacity in the hyperglyc
aemic clamp was also about 30% lower in the LADA-offspring (p = 0.048). The
rates of whole body glucose uptake were similar in both groups. The freque
ncy of low risk HLA-DQB1 genotypes was higher in the LADA-offspring than am
ong Finnish healthy blood donors (p = 0.033). The risk conferring genotypes
were associated with the lowest tertile of insulin secretory capacity in t
he LADA-offspring (p = 0.032). There were no associations between the autoa
ntibodies and early insulin response or insulin secretory capacity within t
he study groups.
Conclusion/interpretation. We conclude that LADA is a familial disease invo
lving most likely gene defects leading to a slow progressive beta-cell dest
ruction and insulin deficiency.