In middle-aged siblings of patients with type 2 diabetes mellitus normal glucose tolerance is associated with insulin resistance and with increased insulin secretion. The SPIDER study.
OBJECTIVE
To evaluate the frequency of impaired glucose tolerance (IGT) and of Type 2 diabetes mellitus (Type 2 DM) in siblings of patients with Type 2 DM, and to assess insulin release and insulin sensitivity in siblings with normal glucose tolerance (NGT), compared with NGT spouses of probands without family history of Type 2 DM.


METHODS
We evaluated 87 families including 103 Type 2 DM patients (87 probands), and we carried out an oral glucose tolerance test (OGTT) in 130 siblings and in 60 spouses. Among NGT subjects, 12 siblings and 16 spouses underwent a low-dose insulin-glucose infusion test (LDIGIT) to evaluate C-peptide release and insulin sensitivity.


RESULTS
After the OGTT, 24 siblings were classified as having Type 2 DM, 31 as IGT, and only 14 spouses as IGT (P=0.0012 vs siblings). NGT siblings (n=75) showed higher insulin levels at 120 min than NGT spouses (n=46) at OGTT, in spite of identical blood glucose levels; at LDIGIT, NGT siblings secreted more C-peptide and showed a lower insulin sensitivity than NGT spouses.


CONCLUSIONS
These data indicate that middle-aged siblings of probands with Type 2 DM have a high frequency of IGT and Type 2 DM, and that NGT siblings have increased insulin resistance and increased insulin secretion when compared with adequate controls.
Pontiroli
A E
AE
Università degli Studi di Milano, Cattedra di Medicina Interna, Istituto San Raffaele, Unità di Malattie Metaboliche, Milano, Italy. antonio.pontiroli@unimi.it
Monti
L D
LD
Costa
S
S
Sandoli
P E
PE
Pizzini
A
A
Solerte
S B
SB
Mantovani
E
E
Piatti
P M
PM
D001786:Blood Glucose / Q000378:metabolism; D003625:Data Collection; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D018454:Spouses
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin