Association Between Abnormal Glycemic Phenotypes and Microvascular Complications of Type 2 Diabetes Mellitus Outpatients in China

Figures & data

Table 1 Characteristics of T2DM Participants with Different Abnormal Glycemic Phenotypes

Characteristics	Overall (n=24,266)	IFH (n=4493)	IPH (n=10,453)	CH (n=9320)	P	P1	P2	P3
Age, years	58.9±11.3	58.0±11.1	58.6±11.6	59.7±11.2	<0.001	<0.001	0.001	<0.001
Sex, male	13,156 (54.2)	2390 (53.2)	5579 (53.4)	5187 (55.7)	<0.001	0.841	0.007	0.001
Diabetes duration, years Median (IQR)	4.2 (2.0–8.4)	3.9 (1.8–7.4)	4.2 (1.6–9.0)	4.4 (2.3–8.4)	<0.001	<0.001	<0.001	<0.001
BMI, Kg/m^2	24.2±3.0	23.9±3.0	24.1±3.0	24.5±3.0	<0.001	0.010	<0.0.01	<0.01
FPG at diagnosis, mmol/L	8.2±2.6	8.5±1.4	6.3±0.8	10.3±2.6	<0.001	<0.001	<0.001	<0.001
2h-PPG at diagnosis, mmol/L	13.8±3.5	9.7±1.3	14.0±2.5	15.5±3.6	<0.001	<0.001	<0.001	<0.001
HbA1c, %	7.4±1.5	7.3±1.3	7.4±1.5	7.8±1.6	<0.001	<0.001	<0.001	<0.001
HbA1c control target	6715 (27.7)	1474 (32.8)	3042 (29.1)	2199 (23.6)	<0.001	<0.001	<0.001	<0.001
SBP, mmHg	132.2±15.0	131.1±14.6	132.4±15.0	132.5±15.2	<0.001	<0.001	<0.001	0.593
DBP, mmHg	81.9±10.9	81.7±10.6	81.8±11.0	82.1±10.9	0.129	0.484	0.063	0.135
Blood pressure control target	14,121 (58.9)	2755 (61.3)	5848 (55.9)	5518 (59.2)	<0.001	<0.001	0.018	<0.001
Self-monitoring of blood glucose	9972 (41.1)	1631 (36.3)	4344(41.6)	3997 (42.9)	<0.001	<0.001	<0.001	0.059
Triglycerides, mmol/L, mmol/L	2.0±1.1	2.1±1.4	1.9±1.0	2.5±1.1	<0.001	<0.001	<0.001	<0.001
Low density lipoprotein cholesterol, mmol/L	2.8±1.0	2.7±1.0	2.8±0.9	2.8±1.0	<0.001	<0.001	<0.001	0.918
Total cholesterol, mmol/L	4.8±1.4	4.9±1.7	4.7±1.4	4.9±1.3	<0.001	<0.001	0.620	<0.001
Lipid target	5942 (24.5)	1177 (26.2)	2498 (23.9)	2267 (24.3)	<0.001	0.003	0.017	0.484
Diabetes treatment
OAD only	13,580(56.0)	2674(59.5)	6462(61.8)	4444(47.7)	<0.001	<0.001	<0.001	<0.001
OAD plus insulin	5185 (21.4)	780(17.4)	1976(18.9)	2429(26.1)	<0.001	<0.001	<0.001	<0.001
OAD plus GLP-1	35 (0.1)	8(0.2)	9(0.1)	18(0.2)	0.113	0.126	0.848	0.042
Insulin only	5054 (20.8)	954(21.2)	1772(17.0)	2328(25.0)	<0.001	<0.001	<0.001	<0.001
GLP-1 only	31 (0.1)	9(0.2)	10(0.1)	12(0.1)	0.259	0.100	0.312	0.486
Lifestyle only	381 (1.6)	68(1.5)	224(2.1)	89(0.9)	<0.001	<0.001	<0.001	<0.001
Economic development level
Underdeveloped	3516 (14.5)	482(10.7)	1444(13.8)	1590(17.1)	<0.001	<0.001	<0.001	<0.001
Intermediately developed	1997(16.5)	749(16.7)	1566(15.0)	1682(18.0)	<0.001	0.009	0.047	<0.001
Developed	16,753(69.0)	3262(72.6)	7443(71.2)	6048(64.9)	<0.001	0.082	<0.001	<0.001
Macrovascular complications
Isolated coronary heart disease	2226(9.2)	332(7.4)	1073(10.3)	821(8.8)	<0.001	<0.001	0.005	0.001
Isolated cerebrovascular disease	758(3.1)	100(2.2)	322(3.1)	336(3.6)	<0.001	0.004	<0.001	0.040
Combined cardiovascular and cerebrovascular disease	478(2.0)	58(1.3)	231(2.2)	189(2.0)	0.001	<0.001	0.002	0.376
Microvascular complications
IDR	1435(5.9)	230 (5.1)	580 (5.6)	625 (6.7)	<0.001	0.288	<0.001	0.001
IDN	781(3.2)	99 (2.2)	322 (3.1)	360 (3.9)	<0.001	0.003	<0.001	0.003
CRN	533(2.2)	58 (1.3)	207 (2.0)	268 (2.9)	<0.001	0.003	<0.001	<0.001

Notes: Data were expressed as mean ± standard deviation or n (%), unless otherwise indicated. Blood pressure target was defined as <140/90 mmHg. Lipid target was defined as TG < 1.7 mmol/L and LDL-C < 2.6 mmo/L. P value was derived from ANOVA, χ² test, Fisher’s exact test or Kruskal–Wallis rank test among three groups. P₁ value was for pairwise comparison between IFH and IPH. P₂ value was for pairwise comparison between IFH and CH. P₃ value was for pairwise comparison between IPH and CH.

Abbreviations: IQR, interquartile range; IFH, isolated fasting hyperglycemia; IPH, isolated postprandial hyperglycemia; CH, combined hyperglycemia; OAD, oral antidiabetic drugs. GLP-1, glucagon-like peptide-1; IDR, isolated diabetic retinopathy; IDN, isolated diabetic nephropathy; CRN, combined diabetic retinopathy and nephropathy.

Figure 1 Cumulative incidence of microvascular diseases stratified by abnormal glycemic phenotype for T2DM participants: (A) isolated diabetic retinopathy (IDR), (B) isolated diabetic nephropathy (IDN), (C) combined diabetic retinopathy and nephropathy (CRN). Log rank test for microvascular diseases of T2DM participants with different abnormal glycemic phenotype (all P<0.05 in pairwise comparison among three phenotypes: IDR, IDN and CRN).

Table 2 Association Between Abnormal Glycemic Phenotypes and Microvascular Disease in Type 2 Diabetes Mellitus Participants

	IDR	IDN	CRN
	Odds Ratio (95% CI)	Odds Ratio (95% CI)	Odds Ratio (95% CI)
Model 1
IFH	1.00 (Reference)	1.00 (Reference)	1.00 (Reference)
IPH	1.23 (1.07–1.40)	1.43 (1.14–1.80)	1.57 (1.17–2.10)
CH	1.38 (1.18–2.62)	1.85 (1.48–2.32)	2.35 (1.77–2.13)
Model fit (C)	0.541	0.555	0.577z
Model 2
IFH	1.00 (Reference)	1.00 (Reference)	1.00 (Reference)
IPH	1.14 (1.05–1.25)	1.35 (1.08–1.70)	1.46 (1.08–1.95)
CH	1.37 (1.17–1.60)	1.82 (1.45–2.28)	2.30 (1.73–3.06)
Age, years	1.03 (1.02–1.03)	1.04 (1.03–1.04)	1.04 (1.04–1.04)
Model fit (C)	0.596	0.620	0.640
Model 3
IFH	1.00 (Reference)	1.00 (Reference)	1.00 (Reference)
IPH	1.11 (1.03–1.21)	1.31 (1.04–1.65)	1.41 (1.05–1.90)
CH	1.33 (1.14–1.56)	1.77 (1.41–2.22)	2.24 (1.67–2.30)
Age, years	1.01 (1.00–1.02)	1.02 (1.01–1.03)	1.02 (1.01–1.03)
Duration of diabetes, years	1.09 (1.08–1.10)	1.09 (1.07–1.10)	1.12 (1.11–1.14)
Model fit (C)	0.663	0.682	0.744
Model 4
IFH	1.00 (Reference)	1.00 (Reference)	1.00 (Reference)
IPH	1.16 (1.05–1.28)	1.37 (1.09–1.73)	1.64 (1.21–2.21)
CH	1.20 (1.02–1.41)	1.59 (1.27–2.01)	1.93 (1.44–2.59)
Age, years	1.01 (1.01–1.02)	1.02 (1.01–1.03)	1.02 (1.01–1.03)
Duration of diabetes, years	1.08 (1.07–1.09)	1.08 (1.07–1.09)	1.11 (1.10–1.13)
Model fit (C)	0.711	0.717	0.792

Notes: Data are odds ratio (95% CI) from logistic regression model. Model 1 has no adjustment of covariable. Model 2 was adjusted for age, sex. Model 3 was adjusted for age, sex. Model 4 was adjusted for age, sex, BMI, self-monitoring of blood glucose, diabetes treatment, the target of blood pressure control, the target of lipid control, HbA1c and economic development level.

Abbreviations: IFH, isolated fasting hyperglycemia; IPH, isolated postprandial hyperglycemia; CH, combined hyperglycemia; IDR, isolated diabetic retinopathy; IDN, isolated diabetic nephropathy; CRN, combined diabetic retinopathy and nephropathy; CI, confidence interval.

Figure 2 Subgroup analysis of association between abnormal glycemic phenotypes and microvascular complication for type 2 diabetes mellitus participants.

Abbreviations: IDR, isolated diabetic retinopathy; IDN, isolated diabetic nephropathy; CRN, combined diabetic retinopathy and nephropathy; IFH, isolated fasting hyperglycemia; IPH, isolated postprandial hyperglycemia; CH, combined hyperglycemia; BMI, body mass index; OR, odds ratio; CI, confidence interval.