Abstract

Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3–6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60′: 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60′ were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort.

Highlights

  • Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism

  • We have shown that pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation are more insulin-sensitive and have an exaggerated risk of postprandial hypoglycaemic events when compared to controls

  • In the context of earlier studies which hypothesized that betatrophin could have beta cell proliferating effects, the lower basal levels and the downregulation of betatrophin during the oral glucose tolerance test (OGTT) in the specific cohort of pregnant women with a history of RYGB operation in the present study could be a consequence of negative feedback in order to prevent aggravation of postprandial hypoglycaemic events in this specific cohort, which were present anyway

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Summary

Introduction

Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. In comparison to normalweight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort. The aim of the present study was to investigate the role of betatrophin on glucose metabolism in the specific cohort of pregnant women with a history of RYGB operation and high risk of postprandial hypoglycaemia

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