In the UK Prospective Diabetes Study, intensive treatment with oral hypoglycemic drugs or insulin for 20 years substantially decreased the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes mellitus (T2DM).1 The ADVANCE, ACCORD and VADT studies have suggested that even further to reduce the blood glucose levels and maintain hemoglobin A1c (HbA1c) below 6.5 % or 6.0 %, there was no significant decrease in the primary cardiovascular endpoint.2., 3., 4. Although blood pressure control, lipid management, weight reduction in overweight or obese individuals, smoking cessation, and intensive glucose control can significantly decrease macrovascular disease, not all patients achieve these targets, even those with microvascular complications.2,4 So, strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and may not completely prevent diabetic complications, which can lead to death from cardiovascular disease.5

Recently, increased glycemic variability (GV) has been reported to be associated with the development and progression of diabetic microvascular and macrovascular complications, exacerbation of hypoglycemic risk, and deterioration of quality of life in patients with T2DM.6., 7., 8., 9., 10., 11., 12. Some short-term GV indices, such as the coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), which are assessed using continuous glucose monitoring (CGM), are also associated with diabetic vascular complications and have been recognized as important indices of glycemic control. Higher MAGE is associated with a higher risk of major adverse cardiovascular events, arterial stiffness, and diabetic peripheral neuropathy (DPN).7,13,14 A lower TIR is an independent risk factor for diabetic retinopathy (DR), DPN albuminuria, and both all-cause and cardiovascular disease (CVD)-related mortality.6,15., 16., 17. However, the mechanisms by which increased GV results in diabetic complications are not fully understood.

Accumulating evidence suggests that inflammatory responses play an important role in the development of microvascular and macrovascular complications related to diabetes.18., 19., 20., 21. CD4+ T-cells can be divided into inflammatory and anti-inflammatory T-cells according to their functionalities and cytokine production.22 Once activated, Th1 and Th17 cells showed inflammatory features, Th1 cells release some cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF)-β, and Th17 cells secrete interleukin (IL) 17, which trigger cell-mediated immunity and promote the inflammatory process. Th2 cells produce IL-4, IL-5, IL-10 and inhibit the proliferation of Th1 cells. Tregs are a powerful immunosuppressive population in inflammatory disorders that can inhibit the proliferation of Th1 and Th17 cells and secrete IL-10 and TGF-β.23

In a previous study of ours, we demonstrated that abnormal T-cell subpopulations were associated with HbA1c levels in patients with T2DM and high levels of HbA1c was an independent risk factor in abnormal T-cell subpopulations.24 However, whether increased GV can result in abnormal T-cell populations other than patients with more severe disease have more abnormalities is not clear. To verify the effects of GV on abnormal T-cell populations, we used CGM to evaluate GV indices in patients with T2DM. The patients were divided into two groups according to MAGE results, and their T-cell populations were assessed.