Correlation Between Glycemic Variability and Diabetic Complications: A Narrative Review

Figures & data

Table 1 Evaluation Parameters for Short-Term and Long-Term Blood Glucose Fluctuations

Parameters of Glycemic Variability	Measurement Methods	Definition
Parameters of the short-term glycemic variability
MDD	SMBG, CGM	Calculate the absolute value of the difference obtained by subtracting the corresponding measurements over 2 consecutive days and then calculate the mean value.^Citation22
AGP	CGM	The distribution of glucose data for a given time point is usually expressed in the form of IQR of AGP.^Citation16,Citation17,Citation22
CV	SMBG, CGM	It was used to measure the stability of blood glucose.
SD	SMBG, CGM	The magnitude of the change in blood glucose compared to the mean blood glucose.
MAGE	SMBG, CGM	Mean difference between peak and minimum values
TIR	SMBG, CGM	The percentage of time within the target range of glucose levels, 70–180 mg/dL (3.9–10.0 mmol/L), within a 24-hour period.^Citation19
TAR	SMBG, CGM	181–250 mg/dL (10.1–13.9mmol/l).^Citation19
TBR	SMBG, CGM	<70 mg/dL (3.8 mmol/l) and <54 mg/dL (2.0mmol/l)
IGP	CGM	IGP=AGP - FPG.^Citation20
GVP	SMBG, CGM	GVP= (L/L0-1) ×100%
Parameters of the long-term glycemic variability
VVV	SMBG, CGM	The inter-following variability of FPG and HbA1c is assessed using FPG and HbA1c obtained from measurements over multiple time periods.^Citation21 SD, CV, VIM and ARV can all be used as indices of VVV.
VIM	SMBG, CGM	Calculations based on logarithmic curve fitting. VIM=SD/mean^β
ASV	SMBG, CGM	Average of the differences between consecutive values.
Variability of HbA1c	SMBG, CGM	Reflects long-term blood glucose fluctuations and expresses its variability in terms of CV, SD, VIM, etc.
HVS	SMBG, CGM	The proportion of the number of HbA1c changes ≥0.5% from the previous time in the total number of HbA1c measurements.^Citation22
Variability of FPG and PPG	SMBG, CGM	It was used to estimate the variability of fasting and postprandial glucose over a follow-up period of months or years, the variability is expressed in terms of CV, SD, VIM, ARV, etc.^Citation22

Abbreviations: AGP, Average glucose profile; ARV, Average real variability; ASV, Average successive variability; CGM, Continuous glucose monitoring; CV, Coefficient of variation; GVP, Glycemic variability percentage; HbA1c, Hemoglobin A1c; HVS, HbA1c variability score; IGP, Incremental glucose peak; MAGE, Mean amplitude of glycemic excursions; MDD, Mean of daily differences; PPG, Postprandial plasma glucose; SD, Standard deviation; SMBG, Self-monitoring of blood glucose; TAR, Time above range; TBR, Time below range; TIR, Time in range; VIM, Variation independent of the mean; VVV, Visit-to-visit variability; IQR, interquartile range.

Table 2 Correlations Between Glycemic Variability Parameters and Diabetic Complications

Parameters of Glycemic Variability	Calculation Method	Macrovascular Complications and Mortality	Microvascular Complications and Neuropathy
Parameters of the short-term glycemic variability
SD	Arithmetic square root of the squared deviation from the mean	Acute myocardial infarction, acute heart failure and sudden cardiac death.	-
MAGE	After removing all blood glucose fluctuations that do not exceed a certain threshold (usually 1 SD), the average is obtained by calculating the amplitude of blood glucose fluctuations according to the direction of the first valid fluctuation	Cerebrovascular diseases such as acute coronary syndrome, coronary artery disease, coronary artery spasm.	-
IGP	IGP=AGP - FPG.^Citation20	Aortic stiffness and poor carotid remodelling.	-
TIR	The percentage of time within the target range of glucose levels, 70–180 mg/dL (3.9–10.0 mmol/L), within a 24-hour period.^Citation19		DR, Microalbuminuria and CAN
Parameters of the long-term glycemic variability
FPG-CV	(SD/mean) ×100%	CVD, ischaemic stroke, accelerated progression of coronary atherosclerosis, poor left heart structure and systolic function, other large vessel lesions and mortality	DPN, PDPN, PAD and other microangiopathy
HbA1c-CV	(SD/mean) ×100%	Coronary atherosclerosis, HFpEF and other large vessel lesions	DN, DPN, CAN and all microangiopathy
FPG-ARV	The average of the differences between successive measurements over a given time period.	CVD	-
HbA1c-VVV	SD, CV, VIM and ARV can all be used as indices of VVV.	Macrovascular disease and mortality	-
FPG-VVV	SD, CV, VIM and ARV can all be used as indices of VVV.	Macrovascular disease and all-cause mortality	Microangiopathy
FPG-VIM	VIM= SD/mean^β	Stroke, myocardial infarction, poor left ventricular reconstruction after infarction and all-cause mortality
FPG-SD	Arithmetic square root of the squared deviation from the mean	Poor left ventricular reconstruction after infarction and other large vessel lesions	All microangiopathy
HbA1c-SD	Arithmetic square root of the squared deviation from the mean	HFpEF and other large vessel lesions	DPN, CAN and all microangiopathy
HVS>60%	The proportion of the number of HbA1c changes ≥0.5% from the previous time in the total number of HbA1c measurements.^Citation22	All-cause mortality and adverse cardiovascular lesions	Diabetic peripheral neuropathy, diabetic foot ulcers and chronic kidney disease
Mean HbA1c	Average value	-	DR in patients with poor glycemic control and peripheral neuropathy

Abbreviations: ARV, Average real variability; CAN, Cardiac autonomic neuropathy; CV, Coefficient of variation; CVD, Cardiovascular disease; DN, Diabetic nephropathy; DR, Diabetic retinopathy; DPN, Diabetic polyneuropathy; DR, Diabetic retinopathy; FPG, Fasting plasma glucose; HFpEF, Heart failure with preserved ejection fraction; HVS, HbA1c variability score; IGP, Incremental glucose peak; MAGE, Mean amplitude of glycemic excursions; PAD, Peripheral artery disease; PDPN, Painful diabetic peripheral neuropathy; SD, Standard deviation; TIR, Time in range; VIM, Variation independent of the mean; VVV, Visit-to-visit variability.

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