Table 1.

Blueberries effects on biomarkers relevant to T2DM and associated metabolic disorders—clinical evidence.

Subjects	Source/Dose	Duration	Main Metabolic Outcome	Ref
Participants with metabolic syndrome	Freeze-dried BB (26 g of powder, equivalent to 150 g of fresh BB)	6 months	= Insulin Resistance = HOMA-IR, HbA1c and QUICKI = Blood pressure ↑ HDL and apoA-1 ↑ Vascular functions ↓ Systemic arterial stiffness ↑ Artery endothelial function	[107]
Obese subjects with metabolic syndrome (pilot study)	Meals enriched with BB	2–4 h	↓ Urinary ketone body levels ↓ Urinary succinate levels ↓ Dimethylamine and trimethylamine ↑ TGF-β mRNA expression from blood mononuclear cells ↓ IL-6 mRNA expression from blood mononuclear cells	[108]
Obese nondiabetic and insulin resistant subjects	Freeze-dried BB (total 45 g powder; ≈ 2 cups of fresh BB)	6 weeks	↑ Insulin sensitivity ↓ Superoxide and total ROS in whole blood and monocytes ↓ Monocytes mRNA expression of TNF-α, TLR4 and IL-6	[109]
Subjects with metabolic syndrome	Freeze-dried BB beverage (50 g, ≈350 g fresh BB)	8 weeks	= Glucose levels and lipid profiles ↓ Blood pressure ↓ Oxidized LDL ↓ Oxidative stress markers (MDA and 4-HNE). = Plasma CRP, IL-6 MPO, adhesion molecules and adiponectin	[110]
T2DM patients	Purified anthocyanins (320 mg/day ≈ 100 gr fresh BB and blackcurrants)	24 weeks	↓ LDL-c, TGs, apo-B and apoC-III ↑ HDL ↓ Fasting glucose and HOMA-IR ↑ Adiponectin and β-hydroxybutyrate ↓ Serum IL-6 and TNF-α ↑ Antioxidant capacity	[111]
Subjects with metabolic syndrome	Lyophilized BB extract (BlueKing®, 2 chewable tablets/day 1200 mg of anthocyanins)	6 months	= Glucose and insulin levels = T-Chol and TGs contents ↓ DNA damage ↓ Vascular endothelium and cell membranes damage ↓ Urinary biomarkers of oxidative stress (8(OH)dG and F2-isoprostanes) ↓ Urinary uric acid ↓ hs-CRP	[112]
T2DM subjects	Single capsule of Mirtoselect® standardized BB extract (0.47 g, 36 % anthocyanins; 50 g of fresh BB	1 day and 2-week washout period	↓ AUC of GTT ↓ Postprandial glucose levels ↓ Plasma insulin levels = Plasma GIP, GLP-1, glucagon and amylin = Plasma MCP-1 inflammatory adipokine and oxidative stress markers	[104]
Men with T2DM	Freeze-dried BB (22 g, equivalent to ∼1 cup fresh per day)	8 weeks	= BW and blood pressure = Fasting plasma glucose and insulin = LDL-c, HDL and T-Chol = CRP ↓ HbA1c and fructosamine ↓ TGs ↓ Hepatic enzymes ALT and AST	[105]
Overweight and obese subjects	BB (50 g serving)	12 weeks	↓ BW, body fat and BMI ↓ LDL-c, and T-Chol ↓ HbA1c, insulin and insulin resistance ↓ Hepatic enzyme AST	[113]
Adults at risk for T2DM	100% wild BB juice (240 mL/day)	7 days	= TGs, glucose and insulin levels = Insulin sensitivity, inflammatory markers, adhesion molecules, oxidative stress, endothelial function, or blood pressure. ↓ Systolic blood pressure ↑ Serum nitrates and nitrites levels	[30]
Obese, nondiabetic, and insulin-resistant subjects	BB powder (45 g, equivalent to ~2 cups of fresh BB)	6 weeks	= BW ↑ Insulin sensitivity = Adiposity, energy intake = Serum TNF-α, MCP-1 and hs-CRP levels	[31]
Patients with non-alcoholic fatty liver disease	Purified anthocyanin (320 mg/d) derived from bilberry and black currant	12 weeks	↓ Glucose intolerance ↓ Plasma TGs ↓ ALT ↓ CK-18 M30, a predictor of NAFLD progression ↓ MPO	[114]
Healthy male individuals	Wild BB powder (25 g in 250 mL of water)	6 weeks	↑ Bifidobacterium spp. ↑ Lactobacillus acidophillus = Bacteroides spp., Prevotella spp., Enterococcus spp., and Clostridium coccoides.	[115]
Healthy old (aged 65–77 years) women	Freeze-dried BBs (38 g/day)	6 weeks	↑ α-microbiota diversity ↑ Healthy microbiota: Faecalibacterium-prauznitzii, B. Intestinihominis, Ruminococcus bromii, Eubacteriu halli. Anaerostipes hadrus and Butyrisimonas virosa	[116]

4-HNE, 4-Hydroxynonenal; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; AUC, area under the curve; CK-18, cytokeratin 18; GIP, gastric inhibitory polypeptide; GTT, glucose tolerance test; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; hs-CRP, high-sensitivity C-reactive protein; MCP-1, monocyte chemoattractant protein 1; MPO, myeloperoxidase; QUICKI, quantitative insulin sensitivity check index; TGF-β, transforming growth factor beta; ↑, increased; ↓, decreased; =, unchanged.