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.RESEARCH DESIGN AND 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
P a t h o p h y s i o l o g y / C o m p l i c a t i o n s
1360DIABETES CARE, VOLUME 23, NUMBER 9, SEPTEMBER 2000Metabolic defects cluster in families with type 2 diabetes uate familial clustering of microalbuminuria (30,31) and has yielded results similar to those of studies performed in offspring of type 2 diabetic patients (29).The second criticism is that in previous studies, control subjects were from the general population. It is known that members of the same family usually share lifestyle in terms of physical activity and diet, whereas control subjects chosen from the general population might have a different lifestyle.The aim of this study was to evaluate the frequency and the possible familial clustering of a series of clinical and metabolic abnormalities in siblings of type 2 diabetic patients using control subjects from the same cohort, i.e., spouses of patients with type 2 diabetes without family history of diabetes.
RESEARCH DESIGN AND METHODS -The study known as SPIDER (an Italian acronym that stands for Studio di Prevenzione dell' Insorgenza del Diabete ad Estensione Regionale, i.e., regional study of prevention of onset of type 2 diabetes) is an ongoing family study aimed at predicting and preventing type 2 diabetes in families with at least one patient affected by type 2 diabetes. The protocol of the study was approved by the Ethics Committee of...