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

• Published in: Diabetologia 2023-11, Vol.66 (11), p.2164-2169
• Main Authors: Oostveen, Reindert F., Kaiser, Yannick, Ståhle, Mia R., Nurmohamed, Nick S., Tzolos, Evangelos, Dweck, Marc R., Kroon, Jeffrey, Murphy, Andrew J., Dey, Damini, Slomka, Piotr J., Verberne, Hein J., Stroes, Erik S. G., Hanssen, Nordin M. J.
• Format: Article
• Language: English
• Subjects: Atorvastatin; Bone marrow; Cardiovascular diseases; Cholesterol; Computed tomography; Coronary artery; Coronary vessels; Diabetes; Diabetes mellitus (non-insulin dependent); Gallium; Human Physiology; Inflammation; Internal Medicine; Low density lipoprotein; Medicine; Medicine & Public Health; Metabolic Diseases; Positron emission tomography; Short Communication; Spleen; Tomography
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-023-05990-9

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 ( 68 Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18 F-fluorodeoxyglucose ( 18 F-FDG). This study set out to investigate whether 68 Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. Methods Individuals aged >50 years with type 2 diabetes underwent 68 Ga-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 68 Ga-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, HbA 1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68 Ga-DOTATATE PET/CT scans. The maximum TBR was −31% (95% CI −50, −12) lower in the coronary arteries, and bone marrow and splenic 68 Ga-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 68 Ga-DOTATATE uptake across the cardio–haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68 Ga-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