{'fraction_non_alphanumeric': 0.022857142857142857, 'fraction_numerical': 0.019740259740259742, 'mean_word_length': 5.551020408163265, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
FGF21 Contributes to Metabolic Improvements Elicited by Exenatide and Pioglitazone in Patients with Type 2 Diabetes.

BACKGROUND
Fibroblast growth factor 21 (FGF21) is increased acutely by carbohydrate ingestion and is elevated in patients with type 2 diabetes (T2D). However, the physiological significance of increased FGF21 in humans remains largely unknown. Objectives and Approach: We examined whether FGF21 contributed to the metabolic improvements observed following treatment of patients with T2D with either triple (metformin/pioglitazone/exenatide) or conventional (metformin/insulin/glipizide) therapy for 3-years. Forty-six patients with T2D were randomized to receive either triple or conventional therapy to maintain HbA1c < 6.5%. A 2-hour 75 g oral glucose tolerance test (OGTT) was performed at baseline and following 3-years of treatment to assess glucose tolerance, insulin sensitivity and β-cell function. Plasma total and bioactive FGF21 was quantitated before and during the OGTT at both visits.


RESULTS
Patients in both treatment arms experienced significant improvements in glucose control, but insulin sensitivity and β-cell function were markedly increased after triple therapy. At baseline, FGF21 levels were regulated acutely during the OGTT in both groups. After treatment, fasting total and bioactive FGF21 were significantly reduced in patients receiving triple therapy, but there was a relative increase in the proportion of bioactive FGF21 compared to conventionally treated subjects. Relative to baseline studies, triple therapy treatment also significantly modified FGF21 levels in response to a glucose load. These changes in circulating FGF21 were correlated with markers of improved glucose control and insulin sensitivity.


CONCLUSIONS
Alterations in the plasma FGF21 profile may contribute to the beneficial metabolic effects of pioglitazone and exenatide in human patients with T2D.