Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review

Table 3 Interventional and observational studies on glycemic control in type 2 diabetes mellitus patients and flow-mediated dilatation outcomes

Ref.	Year	HbA1c (%), mean ± SD	Type of study	Intervention	Sample size	Main findings
Watanabe et al[48]	2000	Fasting glucose 4.9 ± 0.3 mmol/L	Prospective cohort	Troglitazone 400 mg/d for 4 wk in non-DM	13	Improvement on fasting glucose, insulin and FMD
Caballero et al[49]	2003	7.5 ± 1.2 to 7.9 ± 1.5	Prospective randomized double-blinded	Troglitazone 600 mg/d for 12 wk	87	Improvement of FMD in newly diagnosed without CAD
Martens et al[50]	2005	7.1 ± 0.3	Prospective, randomized, crossover, placebo-controlled, double-blinded	Pioglitazone 30 mg/d for 4 wk	20	Improvement of FMD and adiponectin levels
Asnani et al[52]	2006	10 ± 2.3	Prospective randomized double-blinded	Pioglitazone 30 mg/d for 16 wk	20	Improvement of FMD
Chen et al[56]	2011	7.4 ± 1.3	Prospective controlled	Gliclazide 30-90 mg/d for 12 wk	58	Improvement of FMD, ECs and insulin resistance
Naka et al[59]	2012	7.8 ± 0.9 and 8.1 ± 1.3	Open-label randomized	Pioglitazone 30 mg/d or metformin 850 mg/d added to sulfonylureas for 6 mo	36	Improvement of FMD and insulin resistance
Sawada et al[60]	2014	6.9 ± 0.7 vs 7.0 ± 0.4	Randomized prospective	Miglitol 150 mg/d or nateglinide 270 mg/d for 16 wk	104	Improvement of FMD, insulin resistance index and markers of atherogenic dyslipidemia in the α-GI miglitol group
Irace et al[64]	2013	8.9 ± 1.2 and 8.2 ± 1.2	Observational	Exenatide 10-20 μg/d plus metformin vs glimepiride 2-4 mg/d plus metformin for 16 wk	20	Improvement of FMD; Better control on glycemic variability
Nomoto et al[66]	2015	8.6 ± 0.8 and 8.7 ± 0.8	Multicenter, prospective randomized parallel-group comparison	Liraglutide 0.3-0.9 mg/d vs glargine added on metformin and/or sulfonylurea for 14 wk	31	Similar FMD changes and β-cell function protection
Amira et al[68]	2017	Median (range): 8.7 (8.03 – 9.15)	Prospective controlled	Sitagliptin 100 mg/d for 24 wk	80	Improvement of FMD, insulin sensitivity blood pressure and hyperlipidemia
Kubota et al[69]	2012	7.3 ± 0.8	Open-labeled prospective observational single-arm	Sitagliptin 50 mg/d for 12 wk	40	Improvement of FMD and plasma adiponectin increase
Lambadiari et al[70]	2019	8.9 ± 1.8	Prospective cohort	Incretin-based treatment	100	Improvement of FMD and subclinical atherosclerosis after optimal glycemic control
Baltzis et al[71]	2016	7.1 ± 0.8	Randomized, double-blind, placebo-controlled	Linagliptin 5 mg/d vs placebo for 12 wk	40	No improvement in large vessel endothelial function
Takase et al[73]	2018	9.2 ± 1.4	Retrospective preliminary cross-sectional single-center pilot	Canagliflozin 100 mg/d for 4 wk	11	FMD improvement
Shigiyama et al[74]	2017	6.8 ± 0.5 and 6.9 ± 0.5	Prospective, randomized, open-label, blinded end-point, parallel-group, comparative	Dapagliflozin 5 mg/d added on metformin 1500 mg/d for 16 wk	80	Improvement of FMD in newly diagnosed T2DM
Zainordin et al[75]	2020	9.7 ± 1.9	Prospective, randomized, crossover, placebo-controlled, double-blind	Dapagliflozin 10 mg/d vs placebo added on metformin and insulin over 12 wk	81	No difference in FMD between the two groups observed; Significant reduction in surrogate marker of the endothelial function ICAM-1

α-GI: Alpha-glucosidase inhibitor; CAD: Coronary artery disease; DM: Diabetes mellitus; EC: Endothelial cell; FMD: flow-mediated dilatation; SD: Standard deviation; T2DM: Type 2 diabetes mellitus; IL: Interleukin.