Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study
BackgroundAnti-PCSK9 monoclonal antibodies are effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. PCSK9, however, is also expressed in tissues, including the pancreas, and studies on PCSK9 KO mice have shown impaired insulin secretion. Statin treatment is alread...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1124116/full |
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| author | Simona Moffa Teresa Mezza Teresa Mezza Pietro Manuel Ferraro Gianfranco Di Giuseppe Chiara M. A. Cefalo Francesca Cinti Flavia Impronta Umberto Capece Gea Ciccarelli Andrea Mari Alfredo Pontecorvi Andrea Giaccari |
| author_facet | Simona Moffa Teresa Mezza Teresa Mezza Pietro Manuel Ferraro Gianfranco Di Giuseppe Chiara M. A. Cefalo Francesca Cinti Flavia Impronta Umberto Capece Gea Ciccarelli Andrea Mari Alfredo Pontecorvi Andrea Giaccari |
| author_sort | Simona Moffa |
| collection | DOAJ |
| description | BackgroundAnti-PCSK9 monoclonal antibodies are effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. PCSK9, however, is also expressed in tissues, including the pancreas, and studies on PCSK9 KO mice have shown impaired insulin secretion. Statin treatment is already known to affect insulin secretion. Our aim was to conduct a pilot study to evaluate the effect of anti-PCSK9 mAb on glucose metabolism and β-cell function in humans.MethodsFifteen non-diabetic subjects, candidates for anti-PCSK9 mAb therapy, were enrolled. All underwent OGTT at baseline and after 6 months of therapy. During OGTT, insulin secretion parameters were derived from C-peptide by deconvolution (β cell glucose sensitivity). Surrogate insulin sensitivity indices were also obtained from OGTT (Matsuda).ResultsGlucose levels during OGTT were unchanged after 6 months of anti-PCSK9 mAb treatment, as well as insulin and C-peptide levels. The Matsuda index remained unchanged, while β-cell glucose sensitivity improved post-therapy (before: 85.3 ± 65.4; after: 118.6 ± 70.9 pmol min-1m-2mM-1; p<0.05). Using linear regression, we found a significant correlation between βCGS changes and BMI (p=0.004). Thus, we compared subjects with values above and below the median (27.6 kg/m2) and found that those with higher BMI had a greater increase in βCGS after therapy (before: 85.37 ± 24.73; after: 118.62 ± 26.83 pmol min-1m-2mM-1; p=0.007). There was also a significant correlation between βCGS change and Matsuda index through linear regression (p=0.04), so we analyzed subjects who had values above and below the median (3.8). This subgroup analysis showed a slight though not significant improvement in βCGS in more insulin resistant patients, (before: 131.4 ± 69.8; after: 170.8 ± 92.7 pmol min-1m-2mM-1; p=0.066).ConclusionsOur pilot study demonstrates that six-month treatment with anti-PCSK9 mAb improves β-cell function, and does not alter glucose tolerance. This improvement is more evident in patients with greater insulin-resistance (low Matsuda) and higher BMI. |
| first_indexed | 2024-03-13T08:18:05Z |
| format | Article |
| id | doaj.art-d041aae5035c4b3bbd289cbe18497dc1 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T08:18:05Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-d041aae5035c4b3bbd289cbe18497dc12023-05-31T13:36:25ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-05-011410.3389/fendo.2023.11241161124116Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot studySimona Moffa0Teresa Mezza1Teresa Mezza2Pietro Manuel Ferraro3Gianfranco Di Giuseppe4Chiara M. A. Cefalo5Francesca Cinti6Flavia Impronta7Umberto Capece8Gea Ciccarelli9Andrea Mari10Alfredo Pontecorvi11Andrea Giaccari12Centro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyPancreas Unit – Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, ItalyUnità Operativa Semplice Terapia Conservativa della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyInstitute of Neuroscience, National Research Council, Padova, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyCentro Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, ItalyBackgroundAnti-PCSK9 monoclonal antibodies are effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. PCSK9, however, is also expressed in tissues, including the pancreas, and studies on PCSK9 KO mice have shown impaired insulin secretion. Statin treatment is already known to affect insulin secretion. Our aim was to conduct a pilot study to evaluate the effect of anti-PCSK9 mAb on glucose metabolism and β-cell function in humans.MethodsFifteen non-diabetic subjects, candidates for anti-PCSK9 mAb therapy, were enrolled. All underwent OGTT at baseline and after 6 months of therapy. During OGTT, insulin secretion parameters were derived from C-peptide by deconvolution (β cell glucose sensitivity). Surrogate insulin sensitivity indices were also obtained from OGTT (Matsuda).ResultsGlucose levels during OGTT were unchanged after 6 months of anti-PCSK9 mAb treatment, as well as insulin and C-peptide levels. The Matsuda index remained unchanged, while β-cell glucose sensitivity improved post-therapy (before: 85.3 ± 65.4; after: 118.6 ± 70.9 pmol min-1m-2mM-1; p<0.05). Using linear regression, we found a significant correlation between βCGS changes and BMI (p=0.004). Thus, we compared subjects with values above and below the median (27.6 kg/m2) and found that those with higher BMI had a greater increase in βCGS after therapy (before: 85.37 ± 24.73; after: 118.62 ± 26.83 pmol min-1m-2mM-1; p=0.007). There was also a significant correlation between βCGS change and Matsuda index through linear regression (p=0.04), so we analyzed subjects who had values above and below the median (3.8). This subgroup analysis showed a slight though not significant improvement in βCGS in more insulin resistant patients, (before: 131.4 ± 69.8; after: 170.8 ± 92.7 pmol min-1m-2mM-1; p=0.066).ConclusionsOur pilot study demonstrates that six-month treatment with anti-PCSK9 mAb improves β-cell function, and does not alter glucose tolerance. This improvement is more evident in patients with greater insulin-resistance (low Matsuda) and higher BMI.https://www.frontiersin.org/articles/10.3389/fendo.2023.1124116/fullPCSK 9 inhibitiondiabetesβ-cellstatinsprecision medicineBMI |
| spellingShingle | Simona Moffa Teresa Mezza Teresa Mezza Pietro Manuel Ferraro Gianfranco Di Giuseppe Chiara M. A. Cefalo Francesca Cinti Flavia Impronta Umberto Capece Gea Ciccarelli Andrea Mari Alfredo Pontecorvi Andrea Giaccari Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study Frontiers in Endocrinology PCSK 9 inhibition diabetes β-cell statins precision medicine BMI |
| title | Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study |
| title_full | Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study |
| title_fullStr | Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study |
| title_full_unstemmed | Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study |
| title_short | Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study |
| title_sort | effects of pcsk9 inhibition on glucose metabolism and β cell function in humans a pilot study |
| topic | PCSK 9 inhibition diabetes β-cell statins precision medicine BMI |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1124116/full |
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