Increased prevalence of type 2 diabetes mellitus and impaired glucose tolerance in first-degree relatives of girls with a history of precocious pubarche

OBJECTIVE To assess whether abnormal responses to an oral glucose load, dys lipidaemia and hyperandrogenaemia, which are commonly found in girls with a history of precocious pubarche, can also be detected in first-degree relat ives of these patients. PATIENTS AND DESIGN Sixty first-degree relatives (age, 41.4 +/- 4.4 years; BMI, 26.9 +/- 3.3 kg/m(2)) of girls diagnosed with precocious pubarche were studied. The prevalence of gestational diabetes mellitus and the hirsutism score were assessed in the females. The study was performed during the ear ly follicular phase of the menstrual cycle in females and at random in male s. MEASUREMENTS All subjects underwent a standard 75 g 2-h oral glucose tolera nce test (OGTT), Serum lipids and lipoproteins were measured in baseline bl ood samples in all subjects, while serum testosterone, sex hormone-binding globulin (SHBG) levels and the free androgen indices were determined only i n females. Impaired glucose tolerance (IGT) and type 2 diabetes mellitus we re diagnosed according to the criteria of the Expert Committee on the Diagn osis and Classification of Diabetes Mellitus, RESULTS Seven subjects (11.6%) had type 2 diabetes while a further 14 (23.3 %) had IGT; prevalences significantly higher than those reported for the pr esent population of the same age (type 2 diabetes, 2.5% and IGT, 7.5%; P < 0.001 and P < 0.001, respectively). BMIs were similar in patients with eith er normal or abnormal glucose tolerance. Abnormal levels of at least two li pid parameters were found in 40% of subjects. Four out of 10 hirsute women and six non-hirsute women reported gestational diabetes. Mean serum SHBG le vels were lower in female relatives compared with population controls (P < 0.0005). CONCLUSIONS First-degree relatives of girls with precocious pubarche are at a higher risk of impaired glucose tolerance and type 2 diabetes which, in most cases, is accompanied by an unfavourable lipid profile. Hyperandrogeni sm and an increased prevalence of gestational diabetes mellitus are frequen t among females. These data may prove useful in identifying a specific subs et of the population at increased risk of developing metabolic disturbances known to predispose to cardiovascular disease.