Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes

Reindert F. Oostveen; Yannick Kaiser; Mia R. Ståhle; Nick S. Nurmohamed; Evangelos Tzolos; Marc R. Dweck; Jeffrey Kroon; Andrew J. Murphy; Damini Dey; Piotr J. Slomka; Hein J. Verberne; Erik S. G. Stroes; Nordin M. J. Hanssen

doi:https://doi.org/10.1007/s00125-023-05990-9

Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes

Reindert F. Oostveen, Yannick Kaiser, Mia R. Ståhle, Nick S. Nurmohamed, Evangelos Tzolos, Marc R. Dweck, Jeffrey Kroon, Andrew J. Murphy, Damini Dey, Piotr J. Slomka, Hein J. Verberne, Erik S. G. Stroes, Nordin M. J. Hanssen

Research output: Contribution to journal › Article › Academic › peer-review

2 Citations (Scopus)

Abstract

Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT05730634 Graphical Abstract: [Figure not available: see fulltext.]

Original language	English
Pages (from-to)	2164-2169
Number of pages	6
Journal	Diabetologia
Volume	66
Issue number	11
Early online date	2023
DOIs	https://doi.org/10.1007/s00125-023-05990-9
Publication status	Published - Nov 2023

Keywords

Atherosclerosis
Inflammation
Macrophages
Molecular imaging
Statin

Access to Document

https://doi.org/10.1007/s00125-023-05990-9

Cite this

Oostveen, R. F., Kaiser, Y., Ståhle, M. R., Nurmohamed, N. S., Tzolos, E., Dweck, M. R., Kroon, J., Murphy, A. J., Dey, D., Slomka, P. J., Verberne, H. J., Stroes, E. S. G., & Hanssen, N. M. J. (2023). Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes. Diabetologia, 66(11), 2164-2169. https://doi.org/10.1007/s00125-023-05990-9

@article{302f8dd876934c11865fef5846b6a5a9,

title = "Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes",

abstract = "Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT05730634 Graphical Abstract: [Figure not available: see fulltext.]",

keywords = "Atherosclerosis, Inflammation, Macrophages, Molecular imaging, Statin",

author = "Oostveen, {Reindert F.} and Yannick Kaiser and St{\aa}hle, {Mia R.} and Nurmohamed, {Nick S.} and Evangelos Tzolos and Dweck, {Marc R.} and Jeffrey Kroon and Murphy, {Andrew J.} and Damini Dey and Slomka, {Piotr J.} and Verberne, {Hein J.} and Stroes, {Erik S. G.} and Hanssen, {Nordin M. J.}",

note = "Funding Information: PJS has served as a consultant to SYNEKTIK, received research funding from Siemens, has received royalties for software from Cedars-Sinai Medical Center and is associate editor for the Journal of Nuclear Cardiology. NMJH has received honorarium from Novo Nordisk and Boehringer Ingelheim. JK received a preclinical research grant from Oxitope Pharma B.V. NSN is cofounder of Lipid Tools. MRD has served as consultant to Edwards Lifesciences and Medtronic; received research funding from Edwards Lifesciences and Medtronic; and has received speaking fees from NVT. ESGS has received lecturing fees to his institution from Amgen, Sanofi, Esperion, Novartis, NovoNordisk and Ionis Pharmaceuticals. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Funding Information: YK and ESGS were supported by the Netherlands Heart Foundation CVON 2017-20: generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS II]). PJS has received funding from the National Institutes of Health. NMJH is supported by a senior clinical scientist grant from the Netherlands Heart Foundation (grant number 2021T055) Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = nov,

doi = "https://doi.org/10.1007/s00125-023-05990-9",

language = "English",

volume = "66",

pages = "2164--2169",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Verlag",

number = "11",

}

Oostveen, RF, Kaiser, Y, Ståhle, MR, Nurmohamed, NS, Tzolos, E, Dweck, MR, Kroon, J, Murphy, AJ, Dey, D, Slomka, PJ, Verberne, HJ , Stroes, ESG & Hanssen, NMJ 2023, 'Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes', Diabetologia, vol. 66, no. 11, pp. 2164-2169. https://doi.org/10.1007/s00125-023-05990-9

TY - JOUR

T1 - Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes

AU - Oostveen, Reindert F.

AU - Kaiser, Yannick

AU - Ståhle, Mia R.

AU - Nurmohamed, Nick S.

AU - Tzolos, Evangelos

AU - Dweck, Marc R.

AU - Kroon, Jeffrey

AU - Murphy, Andrew J.

AU - Dey, Damini

AU - Slomka, Piotr J.

AU - Verberne, Hein J.

AU - Stroes, Erik S. G.

AU - Hanssen, Nordin M. J.

N1 - Funding Information: PJS has served as a consultant to SYNEKTIK, received research funding from Siemens, has received royalties for software from Cedars-Sinai Medical Center and is associate editor for the Journal of Nuclear Cardiology. NMJH has received honorarium from Novo Nordisk and Boehringer Ingelheim. JK received a preclinical research grant from Oxitope Pharma B.V. NSN is cofounder of Lipid Tools. MRD has served as consultant to Edwards Lifesciences and Medtronic; received research funding from Edwards Lifesciences and Medtronic; and has received speaking fees from NVT. ESGS has received lecturing fees to his institution from Amgen, Sanofi, Esperion, Novartis, NovoNordisk and Ionis Pharmaceuticals. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Funding Information: YK and ESGS were supported by the Netherlands Heart Foundation CVON 2017-20: generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS II]). PJS has received funding from the National Institutes of Health. NMJH is supported by a senior clinical scientist grant from the Netherlands Heart Foundation (grant number 2021T055) Publisher Copyright: © 2023, The Author(s).

PY - 2023/11

Y1 - 2023/11

N2 - Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT05730634 Graphical Abstract: [Figure not available: see fulltext.]

AB - Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of −15% (95% CI −27, −4) and −17% (95% CI −32, −2), respectively. Conclusions/interpretation: 68Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT05730634 Graphical Abstract: [Figure not available: see fulltext.]

KW - Atherosclerosis

KW - Inflammation

KW - Macrophages

KW - Molecular imaging

KW - Statin

UR - http://www.scopus.com/inward/record.url?scp=85167897382&partnerID=8YFLogxK

U2 - https://doi.org/10.1007/s00125-023-05990-9

DO - https://doi.org/10.1007/s00125-023-05990-9

M3 - Article

C2 - 37581619

SN - 0012-186X

VL - 66

SP - 2164

EP - 2169

JO - Diabetologia

JF - Diabetologia

IS - 11

ER -

Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes

Abstract

Keywords

Access to Document

Other files and links

Cite this