Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes.
OBJECTIVE
To test the hypothesis that selected abnormalities cluster in type 2 diabetic families. Offspring of patients with type 2 diabetes have a 40-60% chance of developing type 2 diabetes and an increased frequency of impaired glucose tolerance (IGT) or unknown diabetes. These offspring also show metabolic abnormalities of type 2 diabetes, such as insulin resistance, high insulin and pro-insulin, low HDL cholesterol levels, arterial hypertension, and microalbuminuria.


METHODS
We studied 87 families including at least one type 2 diabetic patient, i.e., 87 probands and 146 siblings; 60 spouses of probands with no family history of diabetes were compared with siblings. Familial clustering was evaluated by 2 methods: concordance of siblings and probands for a given abnormality (method 1) and intraclass correlation coefficients of values within each family (method 2).


RESULTS
At oral glucose tolerance testing, 24 siblings had type 2 diabetes, 31 siblings had IGT, and 14 spouses had IGT (P = 0.0012 vs. siblings). With method 1, familial clustering occurred for microalbuminuria, insulin resistance, arterial hypertension, HDL cholesterol and pro-insulin levels; with method 2, familial clustering was observed for the same variables except for microalbuminuria. With both method 1 and 2, familial clustering for insulin resistance disappeared, whereas familial clustering for arterial blood pressure, HDL cholesterol, and pro-insulin remained after correction for BMI; after further restriction of analysis to probands and to siblings with normal glucose tolerance, familial clustering for pro-insulin was observed only with method 2.


CONCLUSIONS
These data indicate that siblings of diabetic patients are at high risk for selected features of type 2 diabetes.
Pontiroli
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AE
Università degli Studi di Milano, Cattedra di Medicina Interna, and the Istituto Scientifico San Raffaele, Unità de Malattie Metaboliche, Milan, Italy. antonio.pontiroli@unimi.it
Monti
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LD
Pizzini
A
A
Piatti
P
P
D000419:Albuminuria; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D016000:Cluster Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D011384:Proinsulin / Q000097:blood*; D012307:Risk Factors
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D011384:Proinsulin