PET in metabolic syndrome

The metabolic syndrome is a cluster of cardiovascular risk factors, including insulin resistance (elevated fasting glucose or type 2 diabetes), dyslipidemia (elevated triglyceride levels and/or low HDL), obesity (central or abdominal), proinflammatory and prothrombotic state, and hypertension (HTN). Metabolic syndrome contributes to cardiovascular morbidity and mortality, and chronic kidney disease (diabetic kidney disease). The glomerular filtration rate is often elevated in early type 2 diabetes, related to changes in the renal vasculature and autoregulation. High plasma concentrations of vasopressin are associated with metabolic syndrome. Epidemiological evidence connects metabolic syndrome, obesity, diabetes, and non-alcoholic fatty liver disease to reduced bone health and osteoporosis (Musso et al., 2013).

Low-grade chronic inflammation is characteristic for metabolic syndrome. Expanded adipose tissue is a major source of inflammatory cytokines, including leptin, adiponectin, resistin, and visfatin. Higher release of adiponectin from adipose tissue is associated with lower incidence of metabolic syndrome.

Skeletal muscle is responsible for up to 80% of insulin mediated glucose uptake in healthy subjects, but this function is impaired in type 2 diabetes.

Myocardial blood flow (MBF) is higher in subjects with metabolic syndrome; as adenosine-stimulated MBF is similar, the coronary flow reserve (CFR) is reduced (Di Carli et al., 2011).

Obesity

The effects of obesity, insulin resistance, and weight loss on different organs has been studied using PET, for instance glucose and fatty acid metabolism, and perfusion, in the liver, adipose tissue, skeletal muscle, and cardiac muscle (Hannukainen et al., 2014; Iozzo, 2015). The brain regulates eating behaviour, and PET studies on the associations between different neurotransmitter systems and obesity have been conducted (Guzzardi & Iozzo, 2018; Nummenmaa et al., 2018; Pak et al., 2018). Many of the neuropeptides are involved in the regulation of energy homeostasis (van der Klaauw, 2018).

NAFLD and NASH

Increased fat content in the liver (non-alcoholic fatty liver disease, NAFLD) is typical in individuals with metabolic syndrome. NAFLD activity score (NAS) is based on histological features in liver biopsy samples, including steatosis, lobular inflammation, hepatocellular ballooning, fibrosis, and others (Kleiner et al., 2005). Prevalence of NAFLD is ∼25% in the adult population (Paul & Davis, 2018). Hepatocellular lipid accumulation, when continued, can lead to nonalcoholic steatohepatitis (NASH), with inflammation and fibrosis. NASH can progress to cirrhosis or hepatocellular carcinoma (Reccia et al., 2017). Alcoholic fatty liver disease has similar disease stages.

Excessive food intake, saturated fatty acids, cholesterol, and fructose contribute to the development of NAFLD and NASH (Reccia et al., 2017; Musso et al., 2018). NASH and NAFLD are reversible, but the last stage, liver cirrhosis (scarred tissue) cannot be reversed, but requires liver transplantation.

In NAFLD the ability of insulin to suppress gluconeogenesis and production of VLDL is impaired, and the release of C-reactive protein (CRP), fibrinogen, and coagulation factors is increased.

Liver fat content in NAFLD is associated with risk for cardiovascular disease, independent of NASH (Arulanandran et al., 2015). In a FDG study, high liver-to-blood ratio was found to predict cardiovascular events in asymptomatic individuals with NAFLD (Moon et al., 2017), but due to low number of events more studies are needed (Dimitriu-Leen & Scholte, 2017).

Liver function can be assessed with SPECT and PET imaging, using [18F]FDGal, or radioligands for ASGP receptor and mitochondrial MC-I. Fibrosis can be detected with integrin radioligands with PET. Several ultrasound and MRI methods for detecting fibrosis in liver have been developed (Lucero & Brown, 2016; Petitclerc et al., 2017; Di Lascio et al., 2018).


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References:

Armani A, Berry A, Cirulli F, Caprio M. Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte. FASEB J. 2017; 31(10): 4240-4255. doi: 10.1096/fj.201601125RRR.

Di Carli MF, Charytan D, McMahon GT, Ganz P, Dorbala S, Schelbert HR. Coronary circulatory function in patients with the metabolic syndrome. J Nucl Med. 2011; 52(9): 1369-1377. doi: 10.2967/jnumed.110.082883.

Grundy SM (ed.): Atlas of Atherosclerosis and Metabolic Syndrome, 5th ed., Springer, 2011. doi: 10.1007/978-1-4419-5839-6.

Grundy SM. Metabolic syndrome update. Trends Cardiovasc Med. 2016; 364-373. doi: 10.1016/j.tcm.2015.10.004.

Han TS, Lean ME. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease. JRSM Cardiovasc Dis. 2016; 5:2048004016633371. doi: 10.1177/2048004016633371.

Iozzo P. Metabolic imaging in obesity: underlying mechanisms and consequences in the whole body. Ann N Y Acad Sci. 2015; 1353: 21-40. doi: 10.1111/nyas.12880.

Juonala M, Saarikoski LA, Viikari JS, Oikonen M, Lehtimäki T, Lyytikäinen LP, Huupponen R, Magnussen CG, Koskinen J, Laitinen T, Taittonen L, Kähönen M, Kivimäki M, Raitakari OT. A longitudinal analysis on associations of adiponectin levels with metabolic syndrome and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study. Atherosclerosis 2011; 217(1): 234-239. doi: 10.1016/j.atherosclerosis.2011.03.016.

Karmi A, Iozzo P, Viljanen A, Hirvonen J, Fielding BA, Virtanen K, Oikonen V, Kemppainen J, Viljanen T, Guiducci L, Haaparanta-Solin M, Någren K, Solin O, Nuutila P. Increased brain fatty acid uptake in metabolic syndrome. Diabetes 2010; 59(9): 2171-2177. doi: 10.2337/db09-0138.

Labazi H, Trask AJ. Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome. Pharmacol Res. 2017; 123: 114-121. doi: 10.1016/j.phrs.2017.07.004.

Lautamäki R, Borra R, Iozzo P, Komu M, Lehtimäki T, Salmi M, Jalkanen S, Airaksinen KE, Knuuti J, Parkkola R, Nuutila P. Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2006; 291(2): E282-E290. doi: 10.1152/ajpendo.00604.2005.

Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018; 98(4): 2133-2223. doi: 10.1152/physrev.00063.2017.

Tune JD, Goodwill AG, Sassoon DJ, Mather KJ. Cardiovascular consequences of metabolic syndrome. Transl Res. 2017; 183: 57-70. doi: 10.1016/j.trsl.2017.01.001.

Yki-Järvinen H. Non-alcoholic fatty liver disease as a cause and consequence of metabolic syndrome. Lancet Diabetes Endocrinol. 2014; 2: 901-910. doi: 10.1016/S2213-8587(14)70032-4.

Zhang X, Lerman LO. The metabolic syndrome and chronic kidney disease. Transl Res. 2017; 183: 14-25. doi: 10.1016/j.trsl.2016.12.004.



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Created at: 2017-11-07
Updated at: 2018-12-10
Written by: Vesa Oikonen