Endocrine Abstracts

Objective: Impaired glucose homeostasis in PCOS is closely linked to obesity, age and disease phenotype. The potential separate role of reduced GLP-1 response in the development of prediabetes in this population is unclear.

Aim: To compare the GLP-1 response after OGTT in a cohort of obese PCOS with normal glucose tolerance (NGT) and prediabetes.

Design/participants/methods: Case control study recruited 26 obese Caucasian women with PCOS phenotype A. Thirteen of them had normal glucose tolerance (NGT) and 13 had prediabetes defined as having impaired fasting glucose, impaired glucose tolerance or both. They were matched for BMI (37.0±5.5 kg/m², mean ± S.D.) and age (37.2±6.9 years, mean ± S.D.). Serum glucose, insulin, C-peptide, total GLP-1 and total GIP were sampled during 2 h OGTT. Model derived static and dynamic parameters for the assessment of beta cell function and insulin resistance were determined. All patients underwent measurement of androgen profile and whole-body composition by DXA.

Results: Women with prediabets had significantly reduced total GLP-1 after glucose load (GLP-1 in 120 min 3.3±2.1 vs 5.5±2.7 pM in NGT, P=0.014) and decreased incremental area under the curve of GLP-1 (ΔAUC_GLP-1) when compared to NGT group (P=0.016). Values of GLP-1 at 120 min below 3.02 pM predicted prediabetes (sensitivity 0.615 and specificity 0.923). In addition, women with prediabetes had lower insulin and C-peptide values with significant difference at 90 and 120 min of OGTT (P=0.01) and lower insulin sensitivity index (OGIS) (387±69.5 vs 326.6±59.7 in NGT, P=0.04). Despite same BMI, group with prediabetes had higher visceral adipose tissue (VAT) mass, volume and area as measured by DXA (P=0.001 for all). Plasma GLP-1 levels at 120 min was negatively correlated with VAT mass and volume and positively correlated with OGIS. Furthermore, the correlation between the ΔAUC_GLP-1 and the family history of at least one first-degree relative affected with type 2 diabetes was confirmed. The two groups did not differ in total GIP, HOMA-B, MBCI, QUICKI, HOMA-IR and IAI and androgen profile.

Conclusion: GLP-1 response to oral glucose was reduced in obese PCOS with prediabetes independent of age, BMI and disease phenotype. Our findings identify a new separate risk factor for prediabetes in obese PCOS, in particular with predominant visceral obesity.