Studies assessing the impact of GV on cardiovascular outcomes in patients with T2D
| Study | Patients, population | Follow-up (months) | GV measure, metrics | Outcomes | Results |
| ADVANCE Hirakawa et al21 | 4399, T2D | 24 | FG and HbA1c visit-to-visit variation (CV) | Combined macrovascular and microvascular events and all-cause mortality | Increased HbA1c visit-to-visit variation was associated with increased risk of vascular events (p=0.01, HR 1.64, 1.05–2.55), macrovascular events (p=0.02), and mortality (p<0.001, HR 3.31, 1.57–6.98). FG visit-to-visit variation was associated with increased risk of CV events (p<0.001, HR 2.70, 1.65–4.42) and macrovascular (p=0.005) and microvascular (p<0.001) events. |
| DEVOTE 2 Zinman et al49 | 7586, T2D | 24 | SMBG (SD) | MACE, severe hypoglycemia | GV was associated with severe hypoglycemia: HR 4.11 (3.15–5.35); MACE: HR 1.36 (1.12–1.65); and all cause mortality: HR 1.58 (1.23–2.03). |
| Takahashi et al50 | 417, ACS | 39 | CGM (MAGE) | MACCE | MAGE was associated with increased MACCE (23.5% vs 11.6%, p=0.002) and was an independent predictor of poor prognosis (p= 0.045, HR 1.84, 1.01–3.36). |
| Gerbaud et al42 | 327, ACS | 16.9 | SMBG (SD) | MACE | GV cut-off of >2.70 mmol/L was the strongest independent predictive factor of MACE: OR 2.21 (1.64–0.98), p<0.001. |
| VADT Zhou et al51 | 1791, T2D | 84 | FG and HbA1c (CV, ARV) | MACCE | CV and ARV of FG were significantly associated with CVD: CV glucose: p=0.003, OR 1.162 (1.054–1.281); ARV glucose: p=0.0006, OR 1.168 (1.069–1.275). |
| HEART2D Siegelaar et al52 | 1115, AMI | 42 | SMBG (MAGE, MAG, SD) | MACCE | No association between GV and CVD. MAG p=0.57, MAGE p=0.49 and SD p=0.52. |
| DIGAMI 2 Mellbin et al53 | 578, AMI | 12 | BG (RMSE) | Mortality, stroke, reinfarction | No association between GV and complications. Composite endpoint: RMSE p=0.28, HR 1.09 (0.93–1.27), mortality p=0.21, HR 1.14 (0.93–1.38). |
ACS, acute coronary syndrome; ADVANCE, Action in Diabetes and Vascular Disease; AMI, acute myocardial infarction; ARV, average real variability; BG, blood glucose; CGM, continuous glucose monitoring; CV, coefficient of variation; CVD, cardiovascular disease; DEVOTE 2, Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events; DIGAMI 2, Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction; FG, fasting glucose; GV, glycemic variability; HbA1c, glycated hemoglobin; HEART2D, Hyperglycemia and Its Effect after Acute Myocardial Infarction on Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus; MACCE, mayor adverse cardiovascular and cerebrovascular events; MACE, mayor adverse cardiovascular events; MAG, mean absolute glucose; MAGE, mean amplitude of glycemic excursions; RMSE, root mean square error; SMBG, self-monitored blood glucose; T2D, type 2 diabetes; VADT, Veteran Affairs Diabetes Trial.