Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche

Abstract

Prospective epidemiological studies suggest that hyperinsulinaemia, both fasting and postprandial, can be an independent risk factor for the development of cardiovascular disease in non-diabetic subjects [1,2]. Hyperinsulinaemia or insulin resistance or both have been hypothesized to have a major role in dyslipaemia in subjects with both normal and impaired glucose tolerance [3±5]. Hyperinsulinaemia appears to enhance hepatic VLDL synthesis [6,7] and thus could directly contribute to the increased triglyceride and LDL cholesterol values found in these subjects [6,7].The cluster of highly atherogenic metabolic abnormalities of syndrome X (hyperinsulinaemia, glucose intolerance, increased VLDL and triglycerides, decreased HDL cholesterol, and hypertension) are likely to be secondary to the basic abnormality of insulin resistance [3, 4, 6±12] and recent clinical studies in children have provided evidence that the genesis of an atherogenic pattern of risk factors could start in childhood [13,14].High concentrations of lipoprotein (a) Lp(a), an unusual lipoprotein defined by the presence of the Diabetologia (1998) Summary Girls with a history of premature pubarche, i. e. appearance of pubic hair before 8 years of age, show hyperinsulinism in response to an oral glucose tolerance test. As hyperinsulinaemia has a major role in dyslipaemia, and is considered an independent risk factor for cardiovascular disease, we assessed the patterns of plasma insulin concentration after a standard oral glucose tolerance test as well as fasting serum lipid, lipoprotein, and sex hormone-binding globulin concentrations in girls (n = 81) with premature pubarche compared with girls (n = 55) matched with them for stage and bone age to ascertain their metabolic states to identify those potentially at risk for the development of premature cardiovascular disease. Mean serum insulin concentrations were higher in patients at all pubertal stages, and associated with elevated serum triglyceride, very low density cholesterol and very low density triglyceride concentrations (p value range 0.04 to < 0.0001) but reduced sex hormone-binding globulin. Premature pubarche patients also displayed higher low density to high density lipoprotein cholesterol ratios compared with control subjects (p = 0.004 to 0.008). In conclusion, hyperinsulinaemia, decreased sex hormone-binding globulin concentrations and an unfavourable lipid pattern are common features in premature pubarche girls supporting the contention that atherogenic abnormalities composing the metabolic syndrome could start in childhood. To determine the clinical sequelae of such clustering of metabolic deviations, girls who were identified need to be followed up for the potential development of premature cardiovascular disease. [Diabetologia (1998)

Public Health Implications of Altered Puberty Timing

“…In turn, this puts the girls at increased risk for adult complications arising from these changes, namely obesity, type 2 diabetes, dyslipidemia, and cardiovascular disease (metabolic syndrome), and infertility and hirsutism associated with PCOS, although this remains to be demonstrated categorically in longitudinal studies. 9,17,18 Some of these changes (eg, hyperinsulinemia, insulin resistance) are evident at approximately the time of puberty. 19,20 Girls who exhibit these features are frequently obese (notably those of black or Caribbean Hispanic origin), 21 and ϳ30% have marked hyperandrogenism; those with the more marked hyperandrogenism tend to exhibit the greatest insulin resistance and hyperinsulinemia, even after correction for BMI.…”

Resistência à insulina na pubarca precoce - Relação com os androgênios

“…Além disso, a maioria dos estudos referem-se aos achados em adolescentes ou mulheres com a SOP e existem poucos avaliando o papel da hiperinsulinemia na infância (14,15,21,22). Tem sido descrito que os níveis dos androgênios na época da apresentação da PP podem predizer o desenvolvimento do hiperandrogenismo na adolescência (6,23).…”

“…a hiperinsulinemia está presente em muitas meninas com PP desde a infância (16), é um achado comum em adolescentes com hiperandrogenismo (24) e naquelas com hiperandrogenismo e história prévia de PP (15) e está diretamente relacionada com o grau de excesso dos androgênios. Esses autores demonstraram que a hiperinsulinemia, a diminuição da SHBG e um perfil lipídico desfavorável são achados comuns em meninas com PP suportando a hipótese de que as anormalidades aterogênicas que compõem a síndrome metabólica podem começar na infância (22). Nesta casuística, os níveis de SDHEA, T e IAl foram maiores na PP, mas os níveis da G e I de jejum, assim como a AACG, a AACI e a FIGR foram semelhantes aos controles.…”

“…Ibañez e cols. não encontraram correlação entre os androgênios e os diferentes parâmetros medidos durante o TOTG na PP (16) e em adolescentes com hiperandrogenismo (22). Na SOP alguns autores descrevem correlação positiva enquanto outros referem ausência de correlação entre os androgênios e a I, mas também tem sido descrita correlação inversa entre a I e o SDHEA (12,13,26,27).…”

Pubarquia. Adrenarquia. Hirsutismo

“…Si no presenta caracteres sexuales secundarios ni virilización y la edad ósea es acorde con la edad cronológi-ca, se trataría de una adrenarquia precoz, por lo que la paciente no precisaría tratamiento específico, salvo evitar el sobrepeso, y, por tanto, la actitud clínica será de observación por las posibles alteraciones tras la pubertad, sobre todo en las niñas con antecedentes reseñados, ya que hay un 45% que aproximadamente 3 años después de la menarquia pueden presentar hiperandrogenismo ovárico funcional, hiperinsulinemia e hiperlipemia (sobre todo las que tuvieron bajo peso al nacer, aunque es aún motivo de controversia 11 ).…”