Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress

Table 1 Effects of antidiabetics and other agents on β-cell dysfunction in type 2 diabetes through the regulation of inflammatory markers

Ref.	Study population	Intervention	Findings
Nagi and Yudkin[92], 1993	Patients with T2D (n = 27), with an average age between 48 and 56 yr	Received metformin up to a maximum of 850 mg three times a day, for 12 wk	Improved glycemic control and β-cell function, while ameliorating insulin resistance and risk factors for cardiovascular disease, including plasminogen activator inhibitor-1. But had no effect on plasma fibrinogen concentrations and platelet function
Tsunekawa et al[102], 2003	Patients with T2D (n = 17), with an average age of 67 yr	Received glimepiride started from 1 mg daily and increased up to 6 mg daily for 12 wk	Alleviated insulin resistance by decreasing plasma TNF-α levels and reducing those of adiponectin
Dominguez et al[103], 2005	Patients with T2D (n = 10), with an average age of 53 yr	Received etanercept treatment at 25 mg subcutaneously twice weekly for 4 wk	Reduced plasma levels of CRP and interleukin-6 decreased, while also improving β -cell function
Pfützner et al[37], 2006	Patients with T2D (n = 4270), with an average age of 64 yr	Received a combination therapy of peroxisome proliferator activated receptor g agonists and metformin. Disease duration was 5.4 ± 5.6 yr	Increased hs-CRP levels were associated beta-cell dysfunction but showed no correlation with disease duration or glucose control. Patients receiving combination therapy presented the lowest hs-CRP mean values
Hamann et al[95], 2008	Patients with T2D (n = 294), with an average age of 58 yr	Received maximum tolerated doses of rosiglitazone 8 mg plus metformin 2 g/d during the first 12 wk of double-blind treatment for 52 wk	Fixed-dose combination therapy with rosiglitazone/metformin lowered glycated HbA1c and hs-CRP levels over one year of treatment. This was followed by improved beta-cell function suggest and glycaemic control
Pfützner et al[96], 2011	Patients with T2D (n = 146), with an average age of 59 yr	Received a fixed dose combination of 15 mg of pioglitazone with 850 mg of metformin given twice daily for 24 wk	Improved biomarkers of lipid metabolism, β-cell function, activity of the visceral adipose tissue, and chronic systemic inflammation. This was consistent with reduced hs-CRP and increased adiponectin levels
Bellia et al[104], 2012	Patients with T2D (n = 27), with an average age of 56 yr	Received receive either rosuvastatin 20 mg daily or simvastatin 20 mg daily for 6 mo	Effectively reduced hs-CRP levels, but significantly diminished glycemic control and insulin secretion, without affecting insulin sensitivity
Derosa et al[97], 2012	Patients with T2D (n = 167), with an average age of 53 yr	Received metformin gradually titrated until a mean dosage of 2500 ± 500 mg/d was reached for 8 ± 2 mo. Thereafter, patients were randomly assigned to take, vildagliptin at 50 mg twice a day for 12 mo	A combination of metformin and vildagliptin showed better effect in reducing body weight, glycemic control, Homeostatic Model Assessment for Insulin Resistance and improving β-cell function. However, no significant effect was observed for TNF-α levels
Brooks-Worrell and Palmer[105], 2013	Patients with T2D (n = 26), with an average age of between 54 and 58 yr	Received rosiglitazone at 4 mg once/day and increased to twice/day if glycaemic control (HbA1c 70%) not achieved. Glyburide was at 2.5 mg and increased to twice per day up to a maximum of 10 mg twice/day if glycaemic control not achieved	Rosiglitazone reduced islet-specific T cell responses and improved glucagon-stimulated-β-cell secretion, consistent to decreasing in interferon gamma production. This was accompanied by increased adiponectin levels in comparison to glyburide-treated patients
Gagnon et al[106], 2014	Patients with T2D (n = 35), with an average age of 54 yr	Received a combination of calcium carbonate (1200 mg) and cholecalciferol [2000-6000 IU to target 25(OH)D 0.75 nmol/L] for 6 mo	Treatment did not affect glucose tolerance, inflammatory markers (including hs-CRP levels) and β-cell function in patients with T2D, but improved insulin sensitivity in subjects with prediabetes
Zografou et al[98], 2015	Patients with T2D (n = 64), with an average age between 52 and 56 yr	Received metformin at 1700 mg/d plus vildagliptin at 100 mg/d for 6 mo	A combination of metformin and vildagliptin reduced hs-CRP and improved glycemic control and β-cell function
Tao et al[99], 2018	Patients with T2D (n = 21), with an average of 29 yr	Received metformin at 2000 mg/d or saxagliptin at 5 mg/d for 24 wk	Treatment was comparatively effective at reducing body mass index and hs-CRP levels. This was parallel to improved glycemic control, lipid profiles and β-cell function
Zakerkish et al[107], 2019	Patients with T2D (n = 50), with an average of 55 yr	Received Iranian propolis extract at 1000 mg/d for 90 d (3 mo)	Reduction on hs-CRP corresponded with beneficial effects of the extract in decreasing post prandial blood glucose, serum insulin, insulin resistance, and other inflammatory cytokines like TNF-α

T2D: Type 2 diabetes; TNF-α: Tumor necrosis factor-alpha; hs-CRP: Highly sensitive C-reactive protein; HbA1C: Hemoglobin A1C; CRP: C-reactive protein.