Metabolic disorders are complex abnormalities that involve impaired glucose and lipid metabolism, linked to complications such as kidney disease, cardiovascular disease, foot ulcers, retinopathy, and neuropathy.1 The majority of morbidity and early death in diabetes are caused by chronic complications, such as diabetes-associated non-alcoholic fatty liver disease (NAFLD), cardiovascular, renal, and ocular diseases.2 Indeed, a vast proportion of some of the leading causes of death have metabolic disorders associated with diabetes, metabolic syndrome and diabetes as major underlying contributors.

Insulin resistance, hypertension, dyslipidemia, and abdominal obesity are all part of the metabolic syndrome, a concept introduced by Grundy et al in 2001,3–5 replacing Reaven’s Syndrome X introduced in 1988,6 to describe a constellation of factors that together identify a person at increased risk of cardiovascular disease. Obesity, particularly abdominal obesity, is associated with increased release of physiologically active adipokines. Adipokines and cytokines may reduce insulin sensitivity in tissues, causing inflammation and the development of chronic problems. Leptin and adiponectin have been identified as possible markers of obesity-related problems.7 The adipokine revolution, essentially beginning in the 1990s with the discovery of leptin8 and adiponectin,9,10 has resulted in a shift of our scientific understanding of obesity where adipose tissue, containing over 600 adipokines,11 is now viewed as an active endocrine order and obesity is viewed as a disease.12

First described by Thomas Addison in 1836,13 up to 38% of adults worldwide suffer from what has previously been known as non-alcoholic fatty liver disease (NAFLD), now the primary cause of chronic liver disease.14 In recognition of the metabolic basis of the hepatic damage in this condition, it was first suggested that the term NAFLD be changed to “metabolic dysfunction-associated fatty liver disease” (MAFLD) for adults.15 In 2023, the term “metabolic dysfunction-associated steatotic liver disease (MASLD) was adopted; the name chosen to replace non-alcoholic steatohepatitis was metabolic dysfunction-associated steatohepatitis (MASH).16,17 A number of “parallel hits” contribute to the systemic low-grade inflammation and hepatic inflammation in MASLD or MASH, including intestinal dysbiosis, proinflammatory diets, insulin resistance, and lipotoxicity.17

Metabolic alterations are not only associated with increased risk of diabetes and cardiovascular disease but are also related to the risk of cancer. According to a population cohort study that followed 1.3 million Koreans, it was reported that high fasting blood sugar (more than 140 mg/dL) increased the risk of all cancers by 29% for men and 23% for women, respectively.18 A recent meta-analysis of eight observational studies found that lean patients with MASLD had a greater risk of hepatocellular carcinoma, pancreatic and colorectal cancers than non-lean MASLD patients.19 Liver-driven systemic low-grade inflammation promotes the development of cardiovascular inflammation/atherosclerosis, chronic kidney disease, and cancer in a variety of organs, including the colon, stomach, and pancreas.17

Though knowledge is incremental, as with adipokines, it is sometimes revolutionary resulting in complete paradigm shifts in how we see health conditions and their importance. The last half of a century, from Syndrome X and the Metabolic Syndrome to Adipokines, to obesity and type 2 diabetes as diseases rather than just metabolic conditions, and to cancer as a consequence of metabolic disorders, has witnessed such both incremental and revolutionary changes in our understanding of metabolic disorders and their complications. Given the role that metabolic disorders play in many chronic diseases, particularly diabetes, cardiovascular disease, cancer and premature death, this has been much needed knowledge. We look forward to what the coming year and the years ahead bring in furthering our understanding of these topics. We look forward to what the research coming to Diabetes, Metabolic Syndrome and Obesity will reveal.

Data sharing is not applicable to this article as no data were created or analyzed in this study.

JWS – Conceptualization, Methodology, Investigation, Writing – original draft, Writing – review and editing. DAM – Conceptualization, Methodology, Investigation, Writing – original draft, Writing – review and editing. All authors gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

No funding was received.

The author(s) report no conflicts of interest in this work.

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