Background
Any two of the seven criteria below: |
WC ≥ 102/88 cm (Caucasian men and women) or ≥ 90/80 cm (Asian men and women) |
HDL cholesterol < 40 mg/dL (1.0 mmol/L) in men, < 50 mg/dL (1.3 mmol/L) in women or specific drug treatment |
Plasma triglycerides > 150 mg/dL (1.7 mmol/L) or specific drug treatment |
Blood pressure > 130/85 mmHg or specific drug treatment |
Prediabetes |
HOMA-IR score ≥ 2.5 |
hsCRP level > 2 mg/L |
Epidemiology
Obesity
Metabolic syndrome
Adult Treatment Panel III (2005 revision) | International Diabetes Federation |
---|---|
Any three of the five criteria below: | WC ≥ 94 cm (men) or ≥ 80 cm (women) and at least two of the following: |
WC > 102 cm (men) or > 88 cm (women) | Blood glucose > 100 mg/dL (5.6 mmol/L) or diagnosed diabetes |
Blood glucose > 100 mg/dL (5.6 mmol/L) or diagnosed diabetes | HDL cholesterol < 40 mg/dL (1.0 mmol/L) in men, < 50 mg/dL (1.3 mmol/L) in women or specific drug treatment |
HDL cholesterol < 40 mg/dL (1.0 mmol/L) in men, < 50 mg/dL (1.3 mmol/L) in women or specific drug treatment | Plasma triglycerides > 150 mg/dL (1.7 mmol/L) or specific drug treatment |
Plasma triglycerides > 150 mg/dL (1.7 mmol/L) or specific drug treatment | Blood pressure > 130/85 mmHg or specific drug treatment |
Blood pressure > 130/85 mmHg or specific drug treatment |
Diabetes
Pathogenesis
Adipose tissue: a main culprit for metabolic health?
Genetic predisposition
The new liver-pancreas axis, diabetes and NAFLD
The multi-hit hypothesis
NAFLD diagnosis
Liver biopsy
Non-invasive evaluation tests
Imaging techniques
Ultrasonography
Computed tomography
Transient elastography (TE)
Magnetic resonance imaging (MRI)
Scoring systems for estimative of steatosis or fibrosis
Components | Steatosis | Fibrosis | |||||
---|---|---|---|---|---|---|---|
Fatty liver index | NAFLD liver fat score | Hepatic steatosis index | BARD score | APRI | FIB-4 index | NFS | |
Age | X | X | |||||
Sex | X | ||||||
BMI | X | X | X | X | X | ||
Glycemia (or T2D diagnosis) | X | X | X | X | |||
Platelet count | X | X | X | ||||
Albumin | X | ||||||
AST | X | X | X | X | X | X | |
ALT | X | X | X | X | X | ||
GGT | X | ||||||
Triglycerides | X | ||||||
WC | X | ||||||
MetS and insulin | X |
Multistep approach for NAFLD diagnosis and follow-up
NAFLD treatment
Treating obesity in patients with NAFLD
Diet and exercise
GLP-1RAs
Orlistat
Bariatric surgery
Treating NAFLD in patients with MetS
Metformin
Pioglitazone
Vitamin E
Selonsertib and other anti-inflammatory drugs
Treating NAFLD in patients with diabetes
Class of antidiabetic agent | Mechanism of action |
---|---|
Metformin | Reduction in hepatic glucose production and mild insulin sensitizing action in the liver |
Thiazolidinediones | Increase insulin sensitivity in muscle and adipocyte (insulin sensitizers) |
DPP4 inhibitors (gliptins) | Increase in GLP-1 levels, enhancing the glucose-dependent synthesis and secretion of insulin, in addition to glucagon reduction |
GLP-1RAs | Enhancement of the glucose-dependent synthesis and secretion of insulin, in addition to glucagon reduction, delayed gastric emptying and promotion of satiety, resulting in weight loss |
SGLT2 inhibitors | Inhibition of glucose and sodium reabsorption in the proximal tubule of the renal glomerulus, resulting in glycosuria and weight loss |
Sulfonylureas | Glucose-independent secretion of insulin (secretagogue) |
Glinides | Glucose-independent secretion of insulin (secretagogue) |
α-Glucosidase inhibitors | Delay of intestinal absorption of carbohydrates |
Metformin
Thiazolidinediones
Dipeptidyl peptidase 4 (DPP4) inhibitors (gliptins)
GLP-1RAs
SGLT2 inhibitors
Sulfonylurea and glinides
α-Glucosidase inhibitors
Metabolic surgery
Intervention | Obesity | MetS | T2D |
---|---|---|---|
Caloric restriction and exercise | Recommended (despite unavailable evidence of LHI) | Recommended (despite unavailable evidence of LHI) | Recommended (despite unavailable evidence of LHI) |
Orlistat | Modest benefits related to weight loss | # | # |
Bariatric/metabolic surgery | Some benefic effects (unavailable evidence of LHI) | # | # |
Metformin | No confirmed benefit | No confirmed benefit | No substantial impact, but may prevent NASH complications |
Pioglitazone | Benefic effects, including LHI May be considered for BPN | Benefic effects, including LHI May be considered for BPN | Recommended (benefic effects, including LHI) |
Vitamin E | Benefic effects, including LHI May be considered for BPN | Benefic effects, including LHI May be considered for BPN | Limited evidence of benefits Consider in combination with pioglitazone |
DPP4 inhibitors | # | # | Benefits, if any, appears to be limited |
GLP-1RAs | Benefic effects with liraglutide (3 mg/day), similarly effective as structured lifestyle modification (unavailable evidence of LHI) Preliminary evidence of resolution of NASH and no worsening in liver fibrosis with semaglutide (press release) | # | Benefic effects with liraglutide (1.8 mg/day), including limited evidence of LHI Preliminary studies with semaglutide are promising |
SGLT2 inhibitors | # | # | Despite the very promise preliminary results, there is still no evidence of LHI |
Sulfonylureas | # | # | Benefits, if any, appears to be limited with gliclazide |
Glinides | # | # | Poor evidence of LHI with nateglinide |
Acarbose | # | # | Very scarce data |