Glycated hemoglobin is not enough: The role of glycemia risk index for glycemic control assessment in type 1 diabetes

Table 1 Clinical characteristics of the total population and according to glycemia risk index zones, mean ± SD/n (%)

Characteristic	Total (n = 6811)	GRI zone					P value
		Zone A (0-20), (n = 731)	Zone B (21-40), (n = 1851)	Zone C (41-60), (n = 1881)	Zone D (61-80), (n = 1331)	Zone E (81-100), (n = 1021)
Age, years (IQR)	13 (9-21)	15 (11-23)	13 (8-21)	12 (8-25)	13 (9-17)	12 (9-16)	0.150
Age subgroup, children and adolescents	471 (69.5)	42 (57.5)	126 (68.5)	125 (66.8)	100 (75.8)	78 (76.5)	0.034
Sex, female	378 (55.5)	35 (47.9)	111 (60.0)	104 (55.3)	73 (54.9)	55 (53.9)	0.504
Duration, months (IQR)	28 (13-49)	13 (8-34)	23 (11-42)	29 (14-47)	35 (18-54)	35 (20-59)	< 0.001
SBP, mmHg (IQR)	106 (99-117)	107 (101-118)	105 (98-113)	106 (97-118)	107 (100-115)	109 (100-120)	0.087
DBP, mmHg (IQR)	64 (58-71)	67 (60-73)	64 (57-70)	63 (58-71)	65 (57-70)	66 (60-71)	0.136
BMI for children and adolescents, kg/m2 (IQR)	0.14 (-0.56 to 0.84)	0.03 (-0.55 to 0.77)	0.06 (-0.63 to 0.60)	0.15 (-0.56 to 0.87)	0.39 (-0.52 to 1.03)	0.27 (-0.38 to 0.85)	0.2942
BMI for adult, kg/m2 (IQR)	21.33 (19.55-23.19)	21.48 (19.26-22.15)	21.63 (19.97-22.75)	20.43 (19.49-23.52)	21.60 (20.17-23.45)	21.03 (19.77-23.45)	0.489
Treatment method							0.366
CSII	225 (33.0)	19 (26.0)	67 (36.2)	66 (35.1)	45 (33.8)	28 (27.5)
MDI	456 (67.0)	54 (74.0)	118 (63.8)	122 (64.9)	88 (66.2)	74 (72.5)
FCP, pmol/L (IQR)	33 (17-121)	153 (56-209)	58 (17-137)	24 (17-76)	20 (17-77)	17 (17-77)	< 0.001
2hCP, pmol/L (IQR)	53 (17-203)	340 (178-582)	109 (17-266)	35 (17-162)	22 (17-134)	19 (17-115)	< 0.001
HbA1c, % (IQR)	7.20 (6.60-8.00)	6.45 (6.05-6.70)	6.90 (6.56-7.40)	7.30 (6.81-7.90)	7.80 (7.00-8.29)	8.36 (7.23-9.00)	< 0.001
HbA1c < 7%	273 (40.1)	65 (89.0)	98 (53.0)	61 (32.4)	31 (23.3)	18 (17.6)	< 0.001
MG, mmol/L (IQR)	8.10 (7.01-9.41)	7.01 (6.47-7.30)	7.65 (6.84-8.31)	8.39 (7.35-9.37)	9.18 (7.36-10.37)	10.98 (7.95-12.54)	< 0.001
GMI (%)	6.93 ± 0.87	6.33 (6.10-6.45)	6.61 (6.26-6.89)	6.92 (6.48-7.35)	7.26 (6.48-7.77)	8.04 (6.73-8.71)	< 0.001
GMI < 7%	417 (61.2)	73 (100)	158 (85.4)	105 (55.9)	51 (38.3)	30 (29.4)	< 0.001
CV, % (IQR)	39 (34-44)	29 (27-31)	35 (33-38)	40 (38-42)	44 (40-48)	47 (40-52)	< 0.001
CV < 36%	241 (35.4)	73 (100.0)	105 (56.8)	33 (17.6)	13 (9.8)	17 (16.7)	< 0.001
VLow, % (IQR)	1.3 (0.2-3.6)	0.1 (0.0-0.3)	0.8 (0.3-1.7)	1.9 (0.5-3.6)	3.5 (1.1-7.2)	4.2 (0.8-11.5)	< 0.001
Low, % (IQR)	4.5 (2.3-7.1)	2.4 (1.2-3.3)	4.3 (2.3-6.3)	5.3 (2.8-7.5)	5.5 (3.1-9.2)	4.7 (2.3-9.8)	< 0.001
TBR, % (IQR)	6 (3-11)	2 (1-4)	5 (3-8)	7 (4-12)	9 (5-16)	9 (4-22)	< 0.001
TBR < 4%	238 (34.9)	58 (79.5)	71 (38.4)	54 (28.7)	29 (21.8)	26 (25.5)	< 0.001
TAR, % (IQR)	26 (13-41)	9 (5-12)	19 (11-26)	30 (19-39)	40 (25-51)	54 (31-67)	< 0.001
TAR < 25%	329 (48.3)	73 (100.0)	132 (71.4)	67 (35.6)	34 (25.6)	23 (22.5)	< 0.001
High, % (IQR)	19 (11-25)	8 (5-11)	16 (10-22)	22 (16-27)	24 (18-31)	23 (15-27)	< 0.001
VHigh, % (IQR)	5 (1-13)	0 (0-1)	2 (1-5)	8 (3-11)	13 (4-21)	30 (12-37)	< 0.001
TIR, % (IQR)	65 (52-77)	89 (86-91)	76 (70-80)	63 (57-69)	50 (45-60)	37 (29-47)	< 0.001
TIR > 70%	257 (37.7)	73 (100.0)	140 (75.7)	42 (22.3)	2 (1.5)	0 (0.0)	< 0.001
GRI (IQR)	47 (33-69)	15 (11-18)	32 (27-36)	49 (45-54)	69 (64-74)	92 (85-100)	< 0.001
GRI-lo (IQR)	5 (2-10)	2 (1-3)	4 (2-6)	6 (3-10)	8 (4-14)	8 (3-20)	< 0.001
GRI-hi (IQR)	15 (7-27)	5 (2-6)	11 (6-15)	19 (11-25)	27 (14-36)	42 (22-51)	< 0.001
Number of hypoglycemia at night (IQR)	3.0 (1.0-5.0)	1.0 (0.0-3.0)	3.0 (1.0, 5.0)	4.0 (2.0-6.0)	4.0 (2.0-6.0)	2.5 (1.0-6.0)	< 0.001
Number of severe hypoglycemia at night (IQR)	1.00 (0.00-2.00)	0.00 (0.00-0.00)	1.00 (0.00-1.00)	1.00 (0.00-2.00)	2.00 (1.00-4.00)	2.00 (0.00-5.00)	< 0.001

GRI: Glycemia risk index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; BMI: Body mass index; CSII: Continuous subcutaneous insulin infusion; MDI: Multiple daily insulin injection; FCP: Fasting C-peptide; 2hCP: 2-hour C-peptide; MG: Mean glucose; GMI: Glucose management indicator; HbA1c: Glycated hemoglobin; CV: Coefficient of variation; Low: Low-glucose hypoglycemia (glucose level: 3.0 mmol/L to < 3.9 mmol/L); VLow: Very-low-glucose hypoglycemia (glucose level: < 3.0 mmol/L); TBR: Time below range; TAR: Time above range; TIR: Time in range; High: High-glucose hyperglycemia (glucose level: 10.0 mmol/L to 13.9 mmol/L); VHigh: Very-high-glucose hyperglycemia (glucose level: > 13.9 mmol/L); GRI-lo: Hypoglycemia component of glycemia risk index; GRI-hi: The hyperglycemia component of glycemia risk index; IQR: Interquartile range.

Table 2 Comparison of glycemic and metabolic parameters among groups according to cluster analysis, n (%)

Characteristic	Cluster				P value
	Group 1 (n = 256)	Group 2 (n = 91)	Group 3 (n = 232)	Group 4 (n = 102)
TIR (IQR)	61 (53-66)	61 (54-66)	80 (76-86)	35 (29-41)	< 0.001
TIR subgroup					< 0.001
< 50%	42 (16.4)	13 (14.3)	0 (0.0)	102 (100.0)
50%-70%	197 (77.0)	70 (76.9)	0 (0.0)	0 (0.0)
> 70%	17 (6.6)	8 (8.8)	232 (100.0)	0 (0.0)
TAR (IQR)	34 (28-41)	17 (11-24)	11 (7-16)	60 (53-68)	< 0.001
TAR < 25%	29 (11.3)	70 (76.9)	230 (99.1)	0 (0)	< 0.001
TBR (IQR)	5 (3-8)	20 (17-26)	6 (3-10)	4 (1-7)	< 0.001
TBR < 4%	103 (40.2)	0 (0)	85 (36.6)	50 (49.0)	< 0.001
CV (IQR)	40 (37-43)	48 (44-52)	34 (30-37)	42 (36-49)	< 0.001
CV < 36%	53 (20.7)	3 (3.3)	158 (68.1)	27 (26.5)	< 0.001
GRI (IQR)	49 (41-59)	74 (64-85)	27 (18-36)	86 (77-95)	< 0.001
MG, mmol/L (IQR)	8.84 (8.27-9.45)	6.81 (6.13-7.36)	7.01 (6.51-7.43)	11.48 (10.80-12.54)	< 0.001
HbA1c, % (IQR)	7.59 (7.10-8.09)	6.80 (6.40-7.25)	6.60 (6.30-6.94)	8.66 (8.10-9.19)	< 0.001
HbA1c < 7%	45 (17.6)	52 (57.1)	175 (75.4)	1 (1)	< 0.001
GMI, % (IQR)	7.12 (6.87-7.38)	6.24 (5.95-6.48)	6.33 (6.12-6.51)	8.25 (7.96-8.71)	< 0.001
GMI < 7%	100 (39.1)	86 (94.5)	231 (99.6)	0 (0)	< 0.001
High, % (IQR)	24 (22-28)	14 (9-17)	10 (7-14)	28 (23-33)	< 0.001
VHigh, % (IQR)	9 (6-13)	3 (1-6)	1 (0-2)	31 (26-37)	< 0.001
VLow, % (IQR)	1.0 (0.3-2.6)	9.6 (7.1-13.3)	0.8 (0.1-2.1)	0.9 (0.1-2.7)	< 0.001
Low, % (IQR)	3.9 (2.0-5.6)	10.8 (9.2-12.5)	4.9 (2.6-7.2)	2.6 (0.8-4.3)	< 0.001
FCP, pmol/L (IQR)	27 (17-106)	17 (17-51)	76 (17-161)	30 (17-97)	< 0.001
2hCP, pmol/L (IQR)	43 (17-169)	17 (17-125)	159 (17-357)	45 (17-132)	< 0.001
GRI-lo (IQR)	4 (2-7)	18 (15-23)	5 (2-8)	4 (1-6)	< 0.001
GRI-hi (IQR)	21 (17-27)	10 (6-14)	6 (4-9)	45 (39-51)	< 0.001

TBR: Time below range; TAR: Time above range; TIR: Time in range; GRI: Glycemia risk index; CV: Coefficient of variation; MG: Mean glucose; GMI: Glucose management indicator; HbA1c: Glycated hemoglobin; FCP: Fasting C-peptide; 2hCP: 2-hour C-peptide; Low: Low-glucose hypoglycemia (glucose level: 3.0 mmol/L to < 3.9 mmol/L); VLow: Very-low-glucose hypoglycemia (glucose level: < 3.0 mmol/L); High: High-glucose hyperglycemia (glucose level: 10.0 mmol/L to 13.9 mmol/L); VHigh: Very-high-glucose hyperglycemia (glucose level: > 13.9 mmol/L); GRI-lo: Hypoglycemia component of glycemia risk index; GRI-hi: The hyperglycemia component of glycemia risk index; IQR: Interquartile range.

Table 3 Comparison of clinical characteristics and glycemic metrics between baseline and first follow-up in patients with baseline glycated hemoglobin < 7% or glycated hemoglobin ≥ 7% and decreased glycemia risk index, mean ± SD/n (%)

Characteristic	HbA1c < 7%		P value	HbA1c ≥ 7%		P value
	Baseline (n = 31)	First follow-up (n = 31)		Baseline (n = 47)	First follow-up (n = 47)
Age, years (IQR)	11 (7-22)	12 (8-22)	0.612	11 (7-20)	12 (8-21)	0.490
Duration, month (IQR)	24 (8-43)	31 (17-55)	0.137	19 (11-34)	28 (18-40)	0.022
Treatment method			0.799			0.472
CSII	15 (48.4)	14 (45.2)		34 (72.3)	37 (78.7)
MDI	16 (51.6)	17 (54.8)		13 (27.7)	10 (21.3)
HbA1c, % (IQR)	6.4 (6.1-6.8)	6.6 (6.3-6.9)	0.079	8.0 (7.5-8.4)	7.5 (7.1-8.2)	0.044
FCP, pmol/L (IQR)	27 (17-110)	17 (17-101)	0.404	26 (17-98)	23 (17-105)	0.724
2hCP, pmol/L (IQR)	50 (17-271)	17 (17-226)	0.581	69 (17-157)	35 (17-151)	0.957
CV, % (IQR)	39 ± 8	34 ± 7	0.025	38 (33-43)	38 (34-42)	0.958
SD	2.7 ± 0.8	2.6 ± 0.7	0.492	3.6 (3.2-4.2)	3.3 (2.7-3.9)	0.022
GMI, % (IQR)	6.3 ± 0.5	6.5 ± 0.5	0.086	7.4 (7.0-8.1)	6.9 (6.6-7.7)	0.004
VLow, % (IQR)	3.9 (1.1-5.2)	0.9 (0.1-2.3)	0.002	0.5 (0.04-2.2)	1.1 (0.3-2.5)	0.228
Low, % (IQR)	7.9 (5.4-10.4)	3.6 (2.2-7.3)	0.003	3.0 (1.0-5.1)	4.0 (2.1-6.0)	0.137
TBR, % (IQR)	12 (6-17)	5 (2-9)	< 0.001	3.3 (1.1-7.4)	5.4 (2.4-8.5)	0.100
TIR, % (IQR)	73 (64-80)	78 (65-84)	0.217	50 ± 16	62 ± 18	0.001
TAR, % (IQR)	13 (8-21)	12 (8-28)	0.502	45 ± 18	33 ± 18	0.002
High, % (IQR)	11 (7-17)	11 (7-22)	0.458	27 ± 7	22 ± 10	0.003
VHigh, % (IQR)	1.3 (0.2-2.9)	1.9 (0.3-5.1)	0.476	14 (6-27)	7 (2-16)	0.006
GRI-lo (IQR)	10 (5-14)	4 (2-8)	0.001	2.7 (0.9-6.6)	4.4 (2.0-7.2)	0.096
GRI-hi (IQR)	7 (4-12)	7 (4-17)	0.502	27 (20-42)	16 (11-34)	0.002
GRI (IQR)	48 ± 23	33 ± 18	0.007	56 (46-85)	42 (34-66)	0.004

HbA1c: Glycated hemoglobin; CSII: Continuous subcutaneous insulin infusion; MDI: Multiple daily insulin injection; FCP: Fasting C-peptide; 2hCP: 2-hour C-peptide; CV: Coefficient of variation; GMI: Glucose management indicator; Low: Low-glucose hypoglycemia (glucose level: 3.0 mmol/L to < 3.9 mmol/L); VLow: Very-low-glucose hypoglycemia (glucose level: < 3.0 mmol/L); TBR: Time below range; TAR: Time above range; TIR: Time in range; High: High-glucose hyperglycemia (glucose level: 10.0 mmol/L to 13.9 mmol/L); VHigh: Very-high-glucose hyperglycemia (glucose level: > 13.9 mmol/L); GRI-lo: Hypoglycemia component of glycemia risk index; GRI: Glycemia risk index; GRI-hi: The hyperglycemia component of glycemia risk index; IQR: Interquartile range.