Introduction
Metrics and measurement of GV
Various metrics and measure of GV | Description or definition | References |
---|---|---|
Long-term GV | ||
CV | Variation around the mean blood glucose of HbA1c, FPG and PPG between sequential visits | [19] |
SD | Magnitude of variability relative to mean blood glucose of HbA1c, FPG and PPG between sequential visits | [19] |
VIM | Based on logarithmic curve fitting (the natural logarithm of SD over the natural logarithm of the mean) | [22] |
Short-term GV | ||
Within-day or between-day GV | ||
CV | Variation around the mean blood glucose | [18] |
SD | Magnitude of variability relative to mean blood glucose | [18] |
LBGI/HBGI | Measure of frequency and magnitude of hypoglycemia or hyperglycemia | [31] |
ADRR | Sum of the daily peak risks for hypoglycemia and hyperglycemia | [32] |
Within-day GV | ||
MAGE | Mean differences from peaks to nadirs | [23] |
MAG | Absolute differences between sequential readings divided by the time | [8] |
CONGA | Difference between a current blood glucose reading and a reading taken hours earlier | [25] |
TIR | Percentage of time spent within the target glucose range of 3.9–10.0 mmol/L during a 24-h period | |
Between-day GV | ||
MODD | Absolute differences between two glucose values measured at the same time with a 24 h interval | [28] |
AGP/IQRs | Distribution of glucose data at a given timepoint | |
Measuring method of GV | ||
SMBG | Reflected blood glucose fluctuations on the timescale of hours or days | [20] |
CGM | Interstitial glucose measurements at 5 min intervals | |
Flash glucose monitoring | Measured interstitial glucose and indicated direction and speed of glucose change | [36] |
Long‐term GV
Short‐term GV
Within‐day GV
Between‐day GV
The role of GV in diabetic macrovascular and microvascular complications
GV and diabetic macrovascular complications
Metrics of GV | Measuring method | Individuals | Main results | References |
---|---|---|---|---|
Mean daily δ blood glucose | SMBG | 160 patients with or without diabetes | Increased risk of macrovascular complications | [44] |
MAGE | SMBG | 204 patients with poorly controlled T2DM | Associated with coronary artery disease severity | [46] |
MAGE | Flash glucose monitoring | 50 patients with dysglycemia | Positively correlated with coronary artery spasm | [47] |
MAGE and CV | CGM | 35 T2DM patients on clopidogrel therapy | Provided additional diagnostic significance in identifying diabetic patients with HPR | [49] |
SD of blood glucose | SMBG | 327 patients with diabetes and acute coronary syndrome | An independent predictive factor for midterm major cardiovascular events | [51] |
CV of FPG | SMBG | 455 patients with T2DM | A novel risk factor for left cardiac structure and systolic function | [52] |
CV and average real variability of FPG | SMBG | 1791 individuals with T2DM | Significantly associated with cardiovascular disease | [10] |
CV of FPG | SMBG | 3769 individuals | Significantly associated incident diabetes, macrovascular events and mortality | [53] |
VIM of FPG | SMBG | 624,237 subjects with diabetes | Increased the risk of stroke, myocardial infarction, and all-cause mortality | [54] |
CV of visit-to-visit FPG | SMBG | 437 patients with T2DM and ST-segment elevation myocardial infarction | Independently predicted the incidence of left ventricular adverse remodeling | [55] |
CV and VIM of HbA1c | SMBG | 632 patients with T2DM and no history of cardiovascular disease | Increased the combined and additive risk for cardiovascular disease | [56] |
Intra-individual mean, SD and CV of HbA1c | SMBG | 5278 diabetic patients with no history of cardiovascular disease and atherosclerosis | Positively associated with macrovascular complications | [57] |
SD and CV of HbA1c | SMBG | 201 subjects with T2DM and arterial hypertension | Potentially predicted the progression of HFpEF | [58] |
SD and CV of HbA1c | SMBG | 902 patients with heart failure and T2DM | An independent predictive factor of all-cause mortality or composite endpoints | [59] |
SD of HbA1c | CGM | 100 type 2 diabetic patients with preserved left ventricular ejection fraction | Associated with poor left ventricular diastolic dysfunction | [60] |
CV, SD and VIM of HbA1c | SMBG | 420 diabetic patients after stent implantation | Independent predicted the incidence of in-stent restenosis | [61] |
CV of HbA1c and FPG | SMBG | 396 patients with T2DM | Positively associated with accelerated progression of coronary atherosclerosis | [62] |
CV of HbA1c and FPG | SMBG | 63,084 Chinese individuals with diabetes | Increased peripheral artery disease risk | [63] |
GV and diabetic microvascular complications
Metrics of GV | Measuring method | Individuals | Main effects | References |
---|---|---|---|---|
SD of HbA1c | SMBG | 4231 patients with T2DM and albuminuria | Increased the risk of albuminuria | [65] |
CV of HbA1c | SMBG | 1383 T2DM patients | An independent risk factor for deterioration of renal function | [66] |
SD of HbA1c | SMBG | 388 patients with diabetes and chronic kidney disease | Positively associated with the risk of chronic kidney disease progression | [68] |
SD of HbA1c | SMBG | 604 patients with T2DM | Significantly associated with progression of DN | [69] |
MAGE | CGM | 40 patients with T1DM or T2DM | An independent risk factor for DPN | [70] |
TIR | Flash glucose monitoring | 364 individuals with diabetic peripheral neuropathy | Negatively correlated with the risk of painful DN | [71] |
CV of visit-to visit FPG | SMBG | 2773 patients with T2DM | Increased the risk of DPN | [72] |
CV of visit-to visit FPG | SMBG | 36,152 individuals with T2DM | Potent predictors of DPN | [73] |
CV and mean of HbA1c | SMBG | 563 T2DM patients | Significantly increased the risk of DPN | [74] |
Intrapersonal mean, SD and CV of HbA1c | SMBG | 238 patients with T2DM | Strongly associated with the degree of severity of cardiovascular autonomic neuropathy | [75] |
Intrapersonal mean, SD and CV of HbA1c | SMBG | 223 patients with T2DM | Strongly associated with the severity of peripheral neuropathy | [76] |
TIR | CGM | 3262 patients with T2DM | Inversely correlated with the severity of DR | [78] |
CV and SD of HbA1c | SMBG | 220 patients with T1DM | Positively associated with DR and impaired renal function | [80] |
CV of HbA1c | SMBG | 415 patients with T1DM | Independently associated with the risk of DR development | [81] |
The role of GV in DN
The role of GV in DPN
Roles of GV in DR
Relevant mechanisms of GV in diabetic macrovascular and microvascular complications
Mechanism‐based therapeutic strategies
Strategies | Population | Possible mechanisms | References |
---|---|---|---|
Non-pharmacological strategies | |||
CGM | 40 patients with T1DM | Minimized the risk of severe hypoglycemia | [104] |
High-intensity interval training and moderate-intensity continuous training | 15 inactive overweight or obese women | Decreased endothelial cell damage | [108] |
Aerobic and eccentric exercise | 16 healthy subjects | Reduced inflammatory cytokines and oxidative stress markers | [109] |
Low carbohydrate diet | 10 patients with T1DM | Resulted in more time in euglycemia, less time in hypoglycemia | [110] |
Pharmacological strategies | |||
Once-weekly trelagliptin and once-daily alogliptin | 27 patients with T2DM | Improved glycemic control and reduced GV without inducing hypoglycemia | [114] |
GLP-1 RA with basal insulin | 160 patients with T2DM | Lowered hypoglycemia and might contribute to the cardiovascular outcome reduction | [115] |
DPP4 inhibitors combined with metformin | 69 patients with T2DM | Reduced GV and hypoglycemia | [116] |
DPP4 inhibitors combined with metformin | 34 patients with T2DM | Reduced GV and hypoglycemia | [118] |
Metformin plus vildagliptin | 44 patients withT2DM | Attenuated oxidative stress index | [119] |
Empagliflozin as adjunct to insulin | 75 patients with T1DM | Decreased glucose exposure and variability and increased time in glucose target range. | [120] |
SGLT2 inhibitors | 15 patients with T1DM | Improved TIR and the mean glucose level and SD | [121] |