Precision medicine approaches in metabolic disorders and target organ damage: where are we now, and where are we going?

Abstract

In this review, we discuss selected topics which are relevant to implementing precision medicine in metabolic disorders. Personalization of diet and exercise may help in preventing obesity and type 2 diabetes (T2D). Weight loss should be personalized based on age, sex, ethnicity, and coexisting comorbidities. Advances in our understanding of the pathophysiology, genetics, and epigenetics of obesity promise to offer tailored management options. Careful risk assessment is necessary prior to intervention. Risk may be underestimated, e.g., in women, in different ethnic groups, and in people with T2D. More personalized approaches could be useful among persons who failed to respond to traditional risk factor management, such as pharmacological treatment for dyslipidemia and arterial hypertension. Nonalcoholic fatty liver disease/metabolic-associated fatty liver disease (NAFLD/MAFLD) is both a cause and an effect of altered glucose and lipid metabolism. Personalized medicine approaches could be key to identify more effective pharmacological strategies as well as to reverse this common and burdensome metabolic liver disease. Finally, metabolomics could be used to identify relevant biomarkers for cancer diagnosis, staging, and prognostication. Cancers of the colon and rectum, breast, prostate, thyroid, and ovaries illustrate the notion that cancer cell metabolic derangements may be utilized in clinical practice. A true personalization of pharmacotherapies should be pursued especially in obese patients with cancer.

Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction

“…With this evolving scenario, the identification of cofactors for organ dysfunction [ 128 ] , which may contribute to explaining disease heterogeneity and consistently support inherently personalized medicine approaches, has been suggested as a possible solution to overcome the issue of non-responders to conventional therapeutic approaches in metabolic disorders and failures of NASH therapeutic trials [ 9 , 129 , 130 ] . To this end, an ever-increasing awareness of the type, number, and significance of NAFLD/NASH and MAFLD cofactors is a research priority, which opens the way to innovative pathogenic treatment strategies in this field.…”

Precision medicine in nonalcoholic fatty liver disease

“…Additionally, proposals and validation of algorithms are also challenging, as are any attempts to apply these to real‐world hepatological practice 3 . However, with the backset of improved approaches to personalized medicine in metabolic disorders and target organ damage, precision medicine strategies promise novel therapeutic discoveries modeled by systems biology, systems pharmacology and systems medicine approaches 3,38,56–59 …”

“…3 However, with the backset of improved approaches to personalized medicine in metabolic disorders and target organ damage, precision medicine strategies promise novel therapeutic discoveries modeled by systems biology, systems pharmacology and systems medicine approaches. 3,38,[56][57][58][59] Amedeo Lonardo MD *Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy…”

Concise review: gamma-glutamyl transferase - evolution from an indiscriminate liver test to a biomarker of cardiometabolic risk

“…Of note, the study supports the notion that raised GGT values may be a marker of sedentary behavior. Therefore, the recent attempts to introduce GGT as a parameter for stratifying dysmetabolic patients may improve our personalized medicine approach to metabolic disorders and NAFLD [51][52][53] .…”