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, dyslipidaemia and hyperandrogenaemia, which are commonly found in girls with a history of precocious pubarche, can also be detected in first-degree relatives of these patients. PATIENTS AND DESIGN Sixty first-degree relatives (age, 41.4 ± 4.4 years; BMI, 26.9 ± 3.3 kg/m2) 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 early follicular phase of the menstrual cycle in females and at random in males. MEASUREMENTS All subjects underwent a standard 75 g 2-h oral glucose tolerance test (OGTT). Serum lipids and lipoproteins were measured in baseline blood samples in all subjects, while serum testosterone, sex hormone-binding globulin (SHBG) levels and the free androgen indices were determined only in females. Impaired glucose tolerance (IGT) and type 2 diabetes mellitus were diagnosed according to the criteria of the Expert Committee on the Diagnosis 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 present 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 either normal or abnormal glucose tolerance. Abnormal levels of at least two lipid parameters were found in 40% of subjects. Four out of 10 hirsute women and six non-hirsute women reported gestational diabetes. Mean serum SHBG levels 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. Hyperandrogenism and an increased prevalence of gestational diabetes mellitus are frequent among females. These data may prove useful in identifying a specific subset of the population at increased risk of developing metabolic disturbances known to predispose to cardiovascular disease.