Familial diabetes predisposes PCOS patients to insulin resistance (IR), reproductive impairment and hepatic dysfunction: effects of d-chiro inositol (DCI) and alpha lipoic acid (ALA) administration on hepatic insulin extraction (HIE) index

Abstract

Objective

PCOS is a syndrome is characterized by 2 out of 3 of the criteria established during the Rotterdam Consensus Conference. Recently the issue of insulin resistance (IR) has caught attention.

Subjects

A group of overweight/obese PCOS patients (n = 30) have been evaluated before and after 3 months of daily integrative administration of d-chiro inositol (DCI) (500 mg) and alpha lipoic acid (ALA) (300 mg).

Methods

Hormonal and metabolic profiles, oral glucose tolerance test (OGTT) for glucose, insulin and C-peptide response were performed in baseline conditions and after DCI plus ALA treatment. Hepatic Insulin Extraction (HIE) index was computed along the OGTT to evaluate the liver ability in degrading insulin.

Results

The treatment decreased LH, Androstenedione (A), insulin plasma levels, BMI, HOMA index, AST and ALT. Considering patients for the presence (n = 17) or absence of familial diabetes (n = 13), the greatest improvements occurred in the former patients. Insulin response to OGTT was greatly reduced after the treatment interval in PCOS with familial diabetes. HIE computation disclosed that in presence of familial diabetes liver degradation of insulin is reduced thus leaving a higher amount of circulating insulin. DCI plus ALA administration decreased AST and ALT and restored hepatic insulin clearance since HIE profile was improved.

Conclusion

Our study demonstrates that in overweight/obese PCOS the predisposition to familial diabetes triggers IR not only through the endogenous impaired DCI and ALA synthesis but also through a reduced hepatic clearance of insulin. DCI plus ALA administration positively improved hormonal, metabolic profiles as well as liver function.

摘要

目的

PCOS 是一种综合征, 符合鹿特丹共识会议制定的标准中的 3 条标准中的 2 条可诊断。最近, 胰岛素抵抗（IR）问题引起了人们的关注。

受试者

一组超重/肥胖的 PCOS 患者 (n = 30) , 每日给 d-手性肌醇 (DCI) (500 mg) 和 α 硫辛酸 (ALA) (300 mg) 3 个月, 给药前后进行评估.

方法

在基线条件下和给药DCI 加 ALA 治疗后进行激素和代谢谱、口服葡萄糖耐量试验 (OGTT) 以检测葡萄糖、胰岛素和 C 肽反应。OGTT 计算肝脏胰岛素提取 (HIE) 指数以评估肝脏降解胰岛素的能力。

结果

治疗降低了 LH、雄烯二酮 (A)、胰岛素血浆水平、BMI、HOMA 指数、AST 和 ALT。研究患者存在（n = 17）或不存在家族性糖尿病（n = 13）, 家族性糖尿病患者的改善最大。在 PCOS 合并家族性糖尿病的治疗后, 胰岛素对 OGTT 的反应大大降低。 HIE 计算揭示了在存在家族性糖尿病的情况下, 肝脏的胰岛素降解减少, 因此留下更多量的循环胰岛素。由于 HIE 曲线得到改善, DCI 加 ALA 给药降低了 AST 和 ALT 并恢复了肝脏胰岛素清除率。

结论

我们的研究表明, 在超重/肥胖 PCOS 中, 家族性糖尿病的易感性不仅通过内源性 DCI 和 ALA 合成受损, 而且通过降低肝脏对胰岛素的清除率来触发IR。DCI 加 ALA 给药可积极改善激素、代谢谱以及肝功能。

Keywords:

• PCOS
• d-chiro inositol
• alpha lipoic acid
• familial diabetes
• Insulin

关键词:

• 多囊卵巢综合征
• d-手性肌醇
• 硫辛酸
• 家族性糖尿病
• 胰岛素

Conflict of interest

Prof. Alessandro D. Genazzani has been/is consultant and/or lecturer for AlfaSigma (NL), Farmitalia (I), Pfizer (I).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.