What is metabolic disease? Metabolic syndrome as one root cause of several diagnoses

“Metabolic disease” is not a single condition. It is a cluster of five related derangements that together define metabolic syndrome and ultimately produce type 2 diabetes, fatty liver, atherosclerosis and chronic fatigue. Roughly one in three Estonian adults meets the criteria – which usually means the core of metabolism, the action of insulin, has been failing quietly for years.

The five criteria clinicians actually look at

Alberti et al. (Circulation 2009, IDF/AHA harmonised definition) diagnose metabolic syndrome when at least 3 of the following 5 are present:

• Waist circumference: men ≥ 94 cm, women ≥ 80 cm
• Fasting triglycerides ≥ 1.7 mmol/L (or on therapy)
• HDL cholesterol: men < 1.0 mmol/L, women < 1.3 mmol/L
• Blood pressure ≥ 130/85 mmHg (or on therapy)
• Fasting glucose ≥ 5.6 mmol/L (or known type 2 diabetes)

Three of five is the minimum for a diagnosis. But clinically the more useful question is what sits underneath all five: hyperinsulinaemia and insulin resistance (Reaven, Diabetes 1988). Reaven showed already in 1988 that these are not five separate problems but five faces of one cause.

Why waist size is the loudest signal

Subcutaneous fat is a relatively passive energy depot. Visceral fat – the fat that accumulates around the liver, pancreas and gut inside the abdominal cavity – is an active endocrine organ that secretes inflammatory cytokines (TNF-α, IL-6), releases free fatty acids directly into the portal vein, and impairs hepatic insulin sensitivity. Waist growing without hip growing is the textbook metabolic phenotype.

Even in someone with a “normal” BMI of 22–24, a TOFI pattern (thin outside, fat inside) can hide substantial visceral fat with no weight gain. MRI and bioimpedance frequently reveal this in the “outwardly healthy” 40-something patient who presents with fatigue.

Fatty liver: quiet, but reversible

Non-alcoholic fatty liver disease (NAFLD, now MASLD) is more prevalent than type 2 diabetes worldwide – 25–30% of adults (Younossi et al., Hepatology 2019). It is often the earliest lab marker of metabolic disease, before glucose or blood pressure move: mild ALT/AST elevation and steatosis on ultrasound. Fatty liver is fully reversible when insulin sensitivity is restored.

Why losing weight alone is not enough

Weight loss is the single biggest lever, but it is not sufficient by itself. The DiRECT trial (Lean et al., Lancet 2018) showed 46% of patients entering type 2 diabetes remission with an intensive lifestyle program and 10–15 kg of weight loss – but the key was not weight per se, it was where the fat came off: visceral and hepatic depots. Losing the same weight from subcutaneous stores alone does not restore insulin sensitivity.