Background and aims: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients. Methods and results: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7 +/- 5.6 kg/m2), of which 20 underwent bariatric surgery, and 12 nonobese healthy controls. An oral glucose tolerance test (75-g OGTT) was performed in 31 of these obese patients at baseline (T0) and in 14 patients at 6 months after bariatric surgery (T6) to assess plasma glucose, insulin and PCSK9 levels. Plasma PCSK9 levels were also measured in 18 of these obese patients at T0 during a 2-h hyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6 +/- 76.7 ng/mL vs. 201.4 +/- 53.3 ng/mL) and dropped after bariatric surgery (T6; 205.5 +/- 51.7 ng/mL) along with BMI (from 44.1 +/- 5.9 kg/m(2) to 33.1 +/- 5.6 kg/m(2)). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0 +/- 1.8 vs. 5.0 +/- 0.5 mmol/L) and insulin (15.7 +/- 8.3 vs. 5.4 +/- 2.1 mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0 +/- 61.4 ng/mL at 120 min with a hyperinsulinemic peak of 75.1 +/- 40.0 mU/L, at 60 min. Similarly, at T0 insulin infusion during 2-h HEC acutely reduced plasma PCSK9 levels in obese patients. The aforementioned OGTT-induced changes in plasma PCSK9 levels were not observed neither in nonobese healthy controls nor in obese patients after bariatric-surgery weight loss. Conclusions: These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Impact of bariatric surgery-induced weight loss on circulating PCSK9 levels in obese patients
Lupo, Maria Giovanna;De Martin, Sara;Ferri, Nicola
2020
Abstract
Background and aims: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients. Methods and results: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7 +/- 5.6 kg/m2), of which 20 underwent bariatric surgery, and 12 nonobese healthy controls. An oral glucose tolerance test (75-g OGTT) was performed in 31 of these obese patients at baseline (T0) and in 14 patients at 6 months after bariatric surgery (T6) to assess plasma glucose, insulin and PCSK9 levels. Plasma PCSK9 levels were also measured in 18 of these obese patients at T0 during a 2-h hyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6 +/- 76.7 ng/mL vs. 201.4 +/- 53.3 ng/mL) and dropped after bariatric surgery (T6; 205.5 +/- 51.7 ng/mL) along with BMI (from 44.1 +/- 5.9 kg/m(2) to 33.1 +/- 5.6 kg/m(2)). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0 +/- 1.8 vs. 5.0 +/- 0.5 mmol/L) and insulin (15.7 +/- 8.3 vs. 5.4 +/- 2.1 mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0 +/- 61.4 ng/mL at 120 min with a hyperinsulinemic peak of 75.1 +/- 40.0 mU/L, at 60 min. Similarly, at T0 insulin infusion during 2-h HEC acutely reduced plasma PCSK9 levels in obese patients. The aforementioned OGTT-induced changes in plasma PCSK9 levels were not observed neither in nonobese healthy controls nor in obese patients after bariatric-surgery weight loss. Conclusions: These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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