Preadmission Insulin-Treated Type 2 Diabetes Mellitus Patients Had Increased Mortality in Intensive Care Units

Figures & data

Figure 1 The flowchart of study design.

Table 1 Comparison of Main Characteristics at ICU Admission and Treatments During ICU Stay Between Preadmission Non-Insulin-Treated and Preadmission Insulin-Treated T2DM Patients

Variable	Unmatched			P-value	Matched* (1: 1)			P-value
	All Patients (n = 528)	Non-Insulin (n = 300)	Insulin (n = 228)		All Patients (n = 300)	Non-Insulin (n = 150)	Insulin (n = 150)
Baseline characteristics
Age	62.4 ± 12.3	62.0 ± 12.7	62.9 ± 11.7	0.393	62.4 ± 11.3	62.3 ± 11.4	62.5 ± 11.2	0.601
Age range (≥ 60 years)	321 (60.8)	177 (59.0)	144 (63.2)	0.332	190 (63.3)	93 (62.0)	97 (64.7)	0.632
Gender, male	331 (62.7)	190 (63.3)	141 (61.8)	0.726	104 (34.7)	52 (34.7)	52 (34.7)	1.000
Blood glucose >10 mmol/L	354 (67.0)	184 (61.3)	170 (74.6)	0.001	226 (75.3)	113 (75.3)	113 (75.3)	1.000
Diabetic nephropathy	90 (17.0)	28 (9.3)	62 (27.2)	<0.001	34 (11.3)	17 (11.3)	17 (11.3)	1.000
Diabetic retinopathy	19 (3.6)	9 (3.0)	10 (4.4)	0.397	14 (4.7)	8 (5.3)	6 (4.0)	0.584
Hypertension	318 (60.2)	174 (58.0)	144 (63.2)	0.230	168 (56.0)	83 (55.3)	85 (56.7)	0.816
Coronary heart disease	189 (35.8)	96 (32.0)	93 (40.8)	0.037	104 (34.7)	52 (34.7)	52 (34.7)	1.000
COPD	30 (5.7)	16 (5.3)	14 (6.1)	0.692	19 (6.3)	7 (4.7)	12 (8.0)	0.236
Chronic kidney disease	141 (26.7)	52 (17.3)	89 (39.0)	<0.001	68 (22.7)	34 (22.7)	34 (22.7)	1.000
Chronic liver disease	76 (14.4)	46 (15.3)	30 (13.2)	0.481	44 (14.7)	27 (18.0)	17 (11.3)	0.103
Sepsis	71 (13.4)	41 (13.7)	30 (13.2)	0.865	48 (16.0)	27 (18.0)	21 (14.0)	0.345
Acute myocardial infarction	77 (14.6)	44 (14.7)	33 (14.5)	0.950	35 (11.7)	19 (12.7)	16 (10.7)	0.590
APACHE II score	15.0 (10.0–22.3)	15.0 (10.0–21.0)	16.0 (10.0–25.5)	0.521	16.0 (10.0–24.0)	16.0 (10.0–22.0)	16.0 (10.0–27.0)	0.177
Laboratory parameters
Routine blood test
White-cell count, ×10^9 /L	10.1 (7.1–14.4)	10.19 (7.2–14.7)	10.0 (6.9–14.2)	0.593	10.1 (6.9–14.7)	10.3 (7.0–15.3)	10.1 (6.8–14.4)	0.680
Neutrophil count, ×10^9 /L	8.4 (5.4–12.5)	8.25 (5.5–12.7)	8.41 (5.3–12.2)	0.613	8.5 (5.2–13.3)	8.6 (5.3–13.8)	8.4 (5.2–12.9)	0.537
Lymphocyte count, ×10^9 /L	1.0 (0.6–1.4)	0.96 (0.6–1.5)	0.95 (0.54–1.39)	0.457	0.9 (0.6–1.4)	0.9 (0.6–1.3)	1.0 (0.6–1.4)	0.406
Monocyte count, ×10^9 /L	0.6 (0.4–0.8)	0.57 (0.3–0.8)	0.5 (0.4–0.8)	0.518	0.5 (0.3–0.8)	0.5 (0.3–0.8)	0.5 (0.4–0.8)	0.522
Platelet count, ×10^9 /L	170.5 (113.8–232.0)	164.0 (105.0–228.0)	179.0 (115.0–238.0)	0.122	170.0 (108.0–235.0)	161.5 (100.8–219.5)	179.0 (112.5–244.0)	0.112
Hemoglobin, g/L	109.54 ± 28.81	113.9 ± 28.3	103.8 ± 28.5	<0.001	108.5 ± 29.5	110.1 ± 30.4	107.0 ± 28.7	0.349
Blood biochemistry
ALT, U/L	21.0 (13.0–38.0)	22.0 (14.0–40.3)	18.0 (11.0–34.8)	0.003	20.0 (12.0–34.8)	22.0 (14.0–35.0)	18.0 (11.0–34.5)	0.279
AST, U/L	29.0 (19.0–55.0)	31.0 (20.0–69.0)	26.0 (18.0–47.0)	0.007	28.0 (19.0–52.0)	29.0 (19.8–60.8)	25.5 (18.0–46.3)	0.100
Albumin, g/L	32.3 ± 7.0	32.5 ± 7.5	32.1 ± 6.3	0.494	31.5 (26.9–36.9)	30.8 (26.3–37.1)	32.1 (27.5–36.5)	0.566
Total cholesterol, mmol/L	3.6 (2.7–4.4)	3.6 (2.7–4.5)	3.5 (2.7–4.4)	0.405	3.5 (2.6–4.3)	3.4 (2.4–4.4)	3.5 (2.6–4.3)	0.770
Triglyceride, mmol/L	1.4 (1.0–2.1)	1.4 (1.0–2.2)	1.3 (1.0–1.9)	0.239	1.4 (1.0–2.1)	1.4 (1.0–2.2)	1.4 (1.0–1.9)	0.258
HDL, mmol/L	0.8 (0.5–1.0)	0.8 (0.5–1.0)	0.8 (0.6–1.0)	0.137	0.7 (0.5–1.0)	0.7 (0.5–1.0)	0.8 (0.5–1.0)	0.455
LDL, mmol/L	1.9 (1.2–2.8)	2.00 (1.18–2.82)	1.8 (1.3–2.5)	0.441	1.8 (1.2–2.7)	1.8 (1.1–2.8)	1.8 (1.3–2.5)	0.759
Creatinine, μmol/L	106.0 (69.0–228.0)	88.0 (63.0–168.0)	134.5 (81.3–298.5)	<0.001	104.0 (67.0–206.0)	95.0 (63.0–188.8)	108.0 (72.0–229.0)	0.085
Blood urea nitrogen, mmol/L	9.5 (6.0–15.7)	8.3 (5.2–13.7)	10.9 (6.9–19.2)	<0.001	9.0 (6.0–15.0)	8.7 (5.5–13.9)	9.0 (6.3–15.3)	0.150
eGFR, mL/min	56.8 (24.0–92.1)	70.3 (33.2–97.9)	42.1 (15.4–75.3)	<0.001	58.2 (25.0–93.4)	63.9 (27.7–98.0)	52.3 (23.3–89.8)	0.085
NT-ProBNP, pg/mL	2486.0 (599.8–9155.8)	1552.0 (388.0–6992.5)	4476.0 (1144.0–15565.5)	<0.001	2211.5 (608.5–7455.3)	1592.5 (465.0–5865.8)	2818.5 (811.0–8921.8)	0.054
cTnI, pg/mL	33.9 (3.2–489.2)	34.7 (3.7–607.4)	33.3 (2.6–475.3)	0.794	30.1 (5.8–404.1)	41.6 (8.2–404.1)	22.7 (2.4–400.9)	0.682
Glucose, mmol/L	12.2 (9.0–16.2)	11.4 (8.8–15.7)	12.8 (10.0–16.5)	0.014	13.1 (10.1–16.6)	12.8 (10.2–17.1)	13.1 (10.1–16.4)	0.672
Lactate, mmol/L	2.2 (1.5–3.5)	2.5 (1.5–3.7)	2.0 (1.5–3.1)	0.085	2.2 (1.4–3.4)	2.1 (1.4–3.5)	2.2 (1.4–3.4)	0.793
HbA1c, %	7.7 (6.6–9.5)	7.8 (6.6–9.6)	7.6 (6.4–9.4)	0.411	7.9 (6.8–9.6)	8.4 (7.0–9.8)	7.5 (6.6–9.4)	0.183
HbA1c, mmol/mol	61.0 (49.0–80.0)	62.0 (49.0–81.0)	59.0 (47.0–79.0)		63.0 (51.0–81.0)	68.0 (53.0–84.0)	58.0 (49.0–79.0)
Potassium (mmol/L)	4.2 (3.7–4.7)	4.1 (3.7–4.6)	4.4 (3.8–4.9)	0.001	4.2 (3.7–4.7)	4.1 (3.7–4.6)	4.3 (3.8–4.7)	0.328
Sodium (mmol/L)	138.5 (135.4–141.6)	138.7 (135.8–142.0)	138.1 (135.0–140.8)	0.082	138.7 (135.6–141.6)	138.8 (135.8–141.9)	138.7 (135.4–140.9)	0.874
Chloride (mmol/L)	100.9 (96.5–104.8)	101.0 (96.7–105.1)	100.60 (96.5–104.0)	0.389	101.1 (97.5–105.3)	101.2 (97.8–105.4)	101.1 (96.8–105.1)	0.978
Calcium (mmol/L)	2.1 (2.0–2.2)	2.12 (1.99–2.25)	2.12 (1.98–2.23)	0.547	2.1 (2.0–2.2)	2.1 (2.0–2.2)	2.1 (2.0–2.2)	0.925
Bicarbonate (mmol/L)	20.8 (17.0–24.0)	21.0 (17.3–24.0)	20.8 (16.7–24.0)	0.831	20.8 (16.9–24.1)	20.7 (17.2–24.1)	21.2 (16.6–24.1)	0.700
Coagulation function
INR	1.2 (1.1–1.4)	1.18 (1.07–1.37)	1.2 (1.1–1.4)	0.815	1.2 (1.1–1.4)	1.2 (1.1–1.4)	1.2 (1.1–1.4)	0.503
APTT, Sec	41.9 (36.9–50.4)	42.0 (36.6–50.8)	41.9 (37.7–49.2)	0.876	41.9 (37.3–50.3)	42.0 (37.0–52.1)	41.9 (37.6–48.0)	0.580
D-dimer, ug/mL	1.9 (0.8–4.7)	2.1 (0.7–5.5)	1.7 (0.8–3.8)	0.180	1.9 (0.8–4.7)	1.2 (1.1–1.4)	1.8 (0.8–4.4)	0.879
Infection-related indices
C-reactive protein, mg/L	57.5 (11.7–143.9)	59.4 (11.7–162.1)	54.8 (12.3–130.3)	0.215	60.3 (12.5–143.7)	57.1 (12.5–165.5)	63.3 (12.0–134.3)	0.220
ESR, mm/H	27.0 (9.8–54.8)	23.0 (7.5–41.0)	37.0 (12.0–64.0)	0.004	27.0 (11.3–58.8)	25.0 (10.5–59.5)	29.0 (12.0–58.0)	0.410
IL-6, pg/mL	65.1 (23.5–161.6)	64.8 (25.2–165.6)	70.3 (22.5–124.0)	0.660	71.5 (25.8–164.1)	64.9 (34.1–166.4)	75.5 (20.2–130.4)	0.551
Clinical treatment
Average daily insulin consumption in ICU (U/day)	23.4 (10.0–42.0)	18.1 (6.3–37.4)	27.0 (14.1–49.1)	<0.001	26.7 (12.5–47.5)	26.3 (11.2–45.7)	27.4 (14.5–47.9)	0.531
CRRT	226 (42.8)	109 (36.3)	117 (51.3)	0.001	137 (45.7)	64 (42.7)	73 (48.7)	0.297
Mechanical ventilation	334 (63.3)	199 (66.3)	135 (59.2)	0.093	198 (66.0)	101 (67.3)	97 (64.7)	0.626
Glucocorticoids	200 (37.9)	113 (37.7)	87 (38.2)	0.908	106 (35.3)	48 (32.0)	58 (38.7)	0.227
Antibacterial treatment	479 (90.7)	270 (90.0)	209 (91.7)	0.513	274 (91.3)	135 (90.0)	139 (92.7)	0.412

Notes: Data were presented as n (%), mean ± SD, and median (interquartile range). P < 0.05 was considered statistically significant. *Age ± 10 years, gender, glucose >10 mmol/L on admission, diabetic nephropathy, chronic kidney disease, coronary heart disease, ALT ≥ 41 U/L on admission were used for matching.

Abbreviations: T2DM, type 2 diabetes mellitus; ICU, intensive care units; COPD, chronic obstructive pulmonary disease; APACHE, Acute Physiology and Chronic Health Evaluation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR, estimated glomerular filtration rate; NT-proBNP, N-terminal pro-B-type natriuretic peptide; cTnI, cardiac troponin I; HbA1c, glycosylated hemoglobin A1C; INR, international normalized ratio; APTT, activated partial thromboplastin time; ESR, erythrocyte sedimentation rate; IL, interleukin; CRRT, continuous renal replacement therapy; NA, not applicable.

Table 2 Comparison of Clinical Outcomes Between Preadmission Insulin-Treated and Preadmission Non-Insulin Treated T2DM Patients in ICU

Clinical Outcomes	Unmatched			P-value	Matched*			P-value
	All Patients (n = 528)	Non-Insulin (n = 300)	Insulin (n = 228)		All Patients (n = 300)	Non-Insulin (n = 150)	Insulin (n = 150)
Hypoglycemia at ICU stay
Blood glucose ≤ 3.9 mmol/L	59 (11.2)	26 (8.7)	33 (14.5)	0.036	39 (13.0)	16 (10.7)	23 (15.3)	0.229
Blood glucose ≤ 3.0 mmol/L	27 (5.1)	14 (4.7)	13 (5.7)	0.593	21 (7.0)	10 (6.7)	11 (7.3)	0.821
Length of ICU stay (days)	9.0 (5.0–15.0)	8.5 (5.0–14.0)	9 (5–15.8)	0.957	9.0 (5.0–15.0)	8.0 (5.0–14.0)	9.0 (5.0–16.3)	0.531
Mortality	116 (22.0)	60 (20.0)	56 (24.6)	0.210	69 (23.0)	24 (16.0)	45 (30.0)	0.004

Notes: Data were presented as n (%) and median (interquartile range). *Age ± 10 years, gender, glucose >10 mmol/L on admission, diabetic nephropathy, chronic kidney disease, coronary heart disease, ALT ≥ 41 U/L on admission were used for matching.

Abbreviations: T2DM, type 2 diabetes mellitus; ICU, intensive care units.

Table 3 Univariable and Multivariable Cox Proportional Hazards Model for 60-Day Mortality of Critically Ill Patients with T2DM in the Matched Cohort

	Crude HR (95 CI)	P-value	Adjusted HR^† (95 CI)	P-value
Preadmission insulin	1.77 (1.10–2.84)	0.020	1.68 (1.01–2.80)	0.045
Age	1.04 (1.02–1.06)	<0.001	1.04 (1.02–1.07)	0.001
Gender, male	1.15 (0.70–1.90)	0.572	1.31 (0.78–2.21)	0.310
Blood glucose >10 mmol/L	1.18 (0.67–2.06)	0.564	1.02 (0.56–1.85)	0.955
Diabetic nephropathy	0.80 (0.36–1.77)	0.583	/	/
Diabetic retinopathy	0.94 (0.30–3.02)	0.923	/	/
Hypertension	0.95 (0.59–1.54)	0.843	/	/
Coronary heart disease	1.11 (0.66–1.88)	0.697	/	/
COPD	1.34 (0.58–3.11)	0.494	/	/
Chronic kidney disease	0.77 (0.38–1.59)	0.483	/	/
Chronic liver disease	0.84 (0.43–1.65)	0.610	/	/
Sepsis	0.71 (0.36–1.39)	0.314	0.77 (0.38–1.57)	0.475
Acute myocardial infarction	1.50 (0.71–3.16)	0.288	2.19 (1.00–4.82)	0.052
CRRT	1.19 (0.74–1.91)	0.479	/	/
Mechanical ventilation	2.90 (1.44–5.86)	0.003	3.47 (1.67–7.22)	0.001
Glucocorticoids	1.64 (1.01–2.67)	0.046	1.41 (0.85–2.32)	0.180

Notes: ^†The variables with a P value <0.05 in the univariable Cox models, and variables including gender, blood glucose >10 mmol/L on admission, sepsis, acute myocardial infarction were included into the multivariable analysis.

Abbreviations: T2DM, type 2 diabetes mellitus; ICU, intensive care units; COPD, chronic obstructive pulmonary disease; CRRT, continuous renal replacement therapy.

Figure 2 Kaplan–Meier survival curve for the matched cohort of preadmission insulin-treated T2DM patients and preadmission non-insulin-treated T2DM patients in ICU.The adjusted variables included age and gender.

Figure 3 The relationship between mortality and preadmission insulin-treated T2DM patients varied among subgroups divided according to gender, age, blood glucose on ICU admission, and original comorbidities. The final model was adjusted for age, gender, blood glucose >10 mmol/l on admission, sepsis, acute myocardial infarction, except for the stratifying variable.

Table 4 Comparison of Characteristics at ICU Admission and Treatments During ICU Stay Between T2DM Patients Treated Without Insulin Before and After ICU Admission with Preadmission Non-Insulin-Treated and Preadmission Insulin-Treated T2DM Patients

Variable	Unmatched			Group N-N Matched with Preadmission Non-Insulin-Treated Patients^‡		P-value	Group N-N Matched with Preadmission Insulin-Treated Patients^§		P-value
	N-N (n = 50)	P-value (vs N-I)	P-value (vs I–I)	N-N (n = 44)	N-I (n = 44)		N-N (n = 28)	I–I (n = 28)
Baseline characteristics
Age	63.0 (54.8–67.3)	0.491	0.239	63.0 (54.8–67.3)	62.0 (57.0–68.0)	0.519	64.0 (60.3–69.8)	63.0 (58.3–66.0)	0.178
Age range (≥ 60 years)	30 (60.0)	0.894	0.676	28 (63.6)	26 (59.1)	0.661	22 (78.6)	20 (71.4)	0.537
Gender, male	41 (82.0)	0.010	0.007	8 (18.2)	8 (18.2)	1.000	4 (14.3)	4 (14.3)	1.000
Blood glucose >10 mmol/L	26 (52.0)	0.212	0.002	22 (50.0)	22 (50.0)	1.000	18 (64.3)	18 (64.3)	1.000
Diabetic nephropathy	2 (4.0)	0.282	<0.001	1 (2.3)	1 (2.3)	1.000	2 (7.1)	2 (7.1)	1.000
Diabetic retinopathy	0 (0.0)	0.369	0.217	0 (0.0)	3 (6.8)	0.241	0 (0.0)	0 (0.0)	NA
Hypertension	33 (66.0)	0.287	0.705	27 (61.4)	26 (59.1)	0.828	15 (53.6)	13 (46.4)	0.593
Coronary heart disease	42 (84.0)	<0.001	<0.001	36 (81.8)	36 (81.8)	1.000	22 (78.6)	22 (78.6)	1.000
COPD	1 (2.0)	0.485	0.322	1 (2.3)	2 (4.5)	1.000	1 (3.6)	1 (3.6)	1.000
Chronic kidney disease	4 (8.0)	0.096	<0.001	2 (4.5)	2 (4.5)	1.000	3 (10.7)	3 (10.7)	1.000
Chronic liver disease	11 (22.0)	0.237	0.110	9 (20.5)	7 (15.9)	0.580	5 (17.9)	2 (7.1)	0.422
Sepsis	1 (2.0)	0.019	0.023	1 (2.3)	1 (2.3)	1.000	0 (0.0)	0 (0.0)	NA
Acute myocardial infarction	26 (52.0)	<0.001	<0.001	21 (47.7)	21 (47.7)	1.000	10 (35.7)	10 (35.7)	1.000
APACHE II score	6.0 (5.0–8.0)	<0.001	<0.001	6.0 (5.0–8.0)	11.0 (5.0–14.0)	0.115	6.0 (4.8–7.5)	14.5 (7.3–26.8)	0.144
Laboratory parameters
Routine blood test
White-cell count, ×10^9 /L	9.1 (7.6–12.3)	0.331	0.522	9.1 (7.6–12.3)	8.6 (6.7–11.2)	0.172	8.6 (7.6–10.8)	8.2 (6.9–11.8)	0.633
Neutrophil count, ×10^9 /L	7.1 (5.5–10.2)	0.086	0.159	7.1 (5.5–10.2)	6.3 (4.4–8.6)	0.462	6.2 (5.4–8.6)	6.8 (5.0–10.3)	0.387
Lymphocyte count, ×10^9 /L	1.3 (0.9–1.9)	<0.001	<0.001	1.3 (0.9–1.9)	1.2 (0.8–1.7)	0.160	1.4 (1.0–2.0)	1.3 (0.5–1.6)	0.064
Monocyte count, ×10^9 /L	0.6 (0.4–0.8)	0.302	0.179	0.6 (0.4–0.8)	0.6 (0.3–0.8)	0.587	0.6 (0.4–0.8)	0.5 (0.3–0.7)	0.259
Platelet count, ×10^9 /L	217.0 (184.3–268.3)	<0.001	0.001	217.0 (184.3–268.3)	165.0 (101.3–222.3)	0.002	215.0 (180.5–266.8)	223.0 (132.3–307.5)	0.829
Hemoglobin, g/L	132.0 (118.5–139.5)	<0.001	<0.001	132.0 (118.5–139.5)	130.5 (106.3–145.0)	0.503	130.0 (113.5–139.0)	117.5 (96.5–137.8)	0.127
Blood biochemistry
ALT, U/L	29.5 (18.8–48.0)	0.065	0.001	29.5 (18.8–48.0)	22.0 (15.3–44.8.0)	0.517	23.0 (15.8–34.3)	21.5 (13.0–37.8)	0.564
AST, U/L	35.5 (22.5–150.0)	0.090	0.002	35.5 (22.5–150.0)	37.5 (20.5–95.8)	0.378	25.5 (16.5–51.3)	33.5 (18.0–59.5)	0.452
Albumin, g/L	41.0 (38.1–43.4)	<0.001	<0.001	41.0 (38.1–43.4)	37.5 (33.4–42.2)	0.011	41.6 (38.0–43.5)	33.5 (29.4–40.1)	<0.001
Total cholesterol, mmol/L	4.1 (3.4–4.8)	0.008	0.001	4.1 (3.4–4.8)	4.0 (3.3–5.1)	0.642	4.0 (3.4–4.5)	3.6 (2.7–4.4)	0.374
Triglyceride, mmol/L	1.2 (0.8–1.7)	0.046	0.188	1.2 (0.8–1.7)	1.7 (1.0–3.4)	0.035	1.3 (0.9–1.7)	1.2 (0.9–1.4)	0.192
HDL, mmol/L	1.0 (0.8–1.2)	<0.001	0.002	1.0 (0.8–1.2)	0.9 (0.6–1.1)	0.057	0.9 (0.8–1.2)	0.9 (0.7–1.0)	0.140
LDL, mmol/L	2.6 (2.1–3.4)	<0.001	<0.001	2.6 (2.1–3.4)	2.4 (1.7–2.8)	0.215	2.6 (2.1–3.1)	2.3 (1.2–3.0)	0.390
Creatinine, μmol/L	76.5 (64.8–97.3)	0.023	<0.001	76.5 (64.8–97.3)	83.0 (72.0–109.0)	0.051	79.0 (70.8–94.8)	102.0 (72.8–138.8)	0.011
Blood urea nitrogen, mmol/L	5.2 (4.4–6.0)	<0.001	<0.001	5.2 (4.4–6.0)	6.6 (4.8–8.2)	0.019	5.1 (4.4–6.0)	7.2 (5.5–13.0)	0.002
eGFR mL/min	91.0 (73.0–97.9)	0.007	<0.001	91.0 (73.0–97.9)	84.2 (57.3–94.3)	0.073	85.6 (71.7–94.2)	71.1 (40.3–92.2)	0.046
NT-ProBNP, pg/mL	620.5 (158.5–2258.3)	0.003	<0.001	620.5 (158.5–2258.3)	764.0 (282.0–3477.5)	0.437	509.0 (159.5–1737.0)	3453.0 (1069.3–7003.3)	<0.001
cTnI, pg/mL	2649.0 (20.3–41559.2)	<0.001	<0.001	2649.0 (20.3–41559.2)	1129.2 (11.2–5415.2)	0.013	175.5 (14.7–16156.3)	40.5 (5.7–2137.9)	0.030
Glucose, mmol/L	10.1 (8.6–11.5)	0.009	<0.001	10.1 (8.6–11.5)	10.1 (7.6–16.6)	0.012	10.7 (9.0–11.6)	11.2 (8.6–16.0)	0.017
Lactate, mmol/L	1.0 (0.8–7.3)	0.091	0.184	1.0 (0.8–7.3)	2.8 (1.6–3.6)	0.180	0.7 (0.7–0.70)/n = 1	3.4 (1.7–5.6)	NA
HbA1c, %	6.9 (6.3–8.0)	0.005	0.059	6.9 (6.3–8.0)	7.8 (6.4–9.6)	0.024	6.9 (6.3–7.8)	7.5 (6.5–9.4)	0.169
HbA1c, mmol/mol	52.0 (45.0–64.0)			52.0 (45.0–64.0)	62.0 (46.0–81.0)		52.0 (45.0–62.0)	58.0 (48.0–79.0)
Potassium (mmol/L)	4.0 (3.7–4.2)	0.092	<0.001	4.0 (3.7–4.2)	4.0 (3.7–4.3)	0.823	4.0 (3.9–4.1)	4.2 (3.7–4.6)	0.090
Sodium (mmol/L)	138.6 (136.4–140.7)	0.561	0.487	138.6 (136.4–140.7)	139.3 (135.7–140.8)	0.458	138.7 (137.4–141.0)	138.8 (135.7–141.1)	0.674
Chloride (mmol/L)	99.9 (98.0–102.5)	0.195	0.553	99.9 (98.0–102.5)	100.6 (95.1–103.1)	0.815	99.8 (98.2–103.3)	100.6 (97.2–101.9)	0.909
Calcium (mmol/L)	2.2 (2.2–2.3)	<0.001	<0.001	2.2 (2.2–2.3)	2.2 (2.1–2.3)	0.352	2.3 (2.2–2.3)	2.1 (2.0–2.3)	0.009
Bicarbonate (mmol/L)	23.2 (20.7–25.7)	<0.001	0.001	23.2 (20.7–25.7)	21.6 (19.2–24.2)	0.031	24.0 (22.7–26.5)	22.9 (19.0–24.9)	0.102
Coagulation function
INR	1.1 (1.0–1.2)	<0.001	<0.001	1.1 (1.0–1.2)	1.1 (1.0–1.3)	0.097	1.1 (1.0–1.2)	1.1 (1.0–1.3)	0.036
APTT, Sec	40.5 (35.8–172.2)	0.430	0.589	40.5 (35.8–172.2)	39.9 (35.6–48.9)	0.107	39.8 (36.2–56.8)	42.9 (38.6–57.4)	0.773
D-dimer, ug/mL	0.4 (0.3–0.8)	<0.001	<0.001	0.4 (0.3–0.8)	0.9 (0.4–5.2)	0.004	0.4 (0.3–0.8)	1.3 (0.4–5.2)	<0.001
Infection-related indices
C-reactive protein, mg/L	6.7 (2.1–17.5)	<0.001	<0.001	6.7 (2.1–17.5)	47.1 (3.9–104.3)	<0.001	5.7 (2.6–16.2)	21.4 (3.6–122.0)	0.048
ESR, mm/H	10.0 (4.0–19.5)	0.001	<0.001	10.0 (4.0–19.5)	11.0 (5.8–30.3)	0.056	14.0 (6.0–33.5)	8.0 (5.0–53.0)	0.208
IL-6, pg/mL	14.9 (9.7–33.6)	0.011	0.015	14.9 (9.7–33.6)	104.9 (36.0–316.3)	0.010	6.3 (6.3–6.3)/n = 1	/	NA
Clinical treatment
Average daily insulin consumption in ICU (U/day)	/	NA	NA	/	22.6 (5.0–49.5)	NA	/	21.8 (13.8–48.0)	NA
CRRT	1 (2.0)	<0.001	<0.001	1 (2.3)	6 (13.6)	0.110	0 (0.0)	8 (28.6)	0.004
Mechanical ventilation	2 (4.0)	<0.001	<0.001	1 (2.3)	20 (45.5)	<0.001	0 (0.0)	11 (39.3)	<0.001
Glucocorticoids	8 (16.0)	0.003	0.003	7 (15.9)	11 (25.0)	0.290	5 (17.9)	15 (53.6)	0.005
Antibacterial treatment	26 (52.0)	<0.001	<0.001	23 (52.3)	28 (63.6)	0.280	15 (53.6)	24 (85.7)	0.009

Notes: Data were presented as n (%) and median (interquartile range). Group N-N was composed of T2DM patients treated without insulin before and after ICU admission. Group N-I was composed of patients who received treatment without insulin before ICU admission but received insulin treatment after ICU admission, which also referred to preadmission non-insulin treated T2DM patients. Group I-I was composed of patients who received insulin treatment before and after ICU admission, which also referred to preadmission insulin-treated T2DM patients. P < 0.05 was considered statistically significant. ^‡And ^§Age ± 10 years, gender, blood glucose >10 mmol/L on admission, diabetic nephropathy, chronic kidney disease, coronary heart disease, sepsis, acute myocardial infarction on admission were used for matching.

Abbreviations: T2DM, type 2 diabetes mellitus; ICU, intensive care units; COPD, chronic obstructive pulmonary disease; APACHE, Acute Physiology and Chronic Health Evaluation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR, estimated glomerular filtration rate; NT-proBNP, N-terminal pro-B-type natriuretic peptide; cTnI, cardiac troponin I; HbA1c, glycosylated hemoglobin A1C; INR, international normalized ratio; APTT, activated partial thromboplastin time; ESR, erythrocyte sedimentation rate; IL, interleukin; CRRT, continuous renal replacement therapy; NA, not applicable.

Table 5 Comparison of Clinical Outcomes Between T2DM Patients Treated Without Insulin Before and After ICU Admission with Readmission Non-Insulin-Treated and Preadmission Insulin-Treated T2DM Patients

Clinical Outcomes	Unmatched			Group N-N Matched with Preadmission Non-Insulin-Treated Patients^‡		P-value	Group N-N Matched with Preadmission Insulin-Treated Patients^§		P-value
	N-N (n = 50)	P- value vs N-I	P-value vs I–I	N-N (n = 44)	N-I (n = 44)		N-N (n = 28)	I–I (n = 28)
Hypoglycemia at ICU stay
Blood glucose ≤ 3.9 mmol/L	1 (2.0)	0.149	0.015	1 (2.3)	3 (6.8)	0.616	1 (3.6)	5 (17.9)	0.193
Blood glucose ≤ 3.0 mmol/L	0 (0.0)	0.234	0.134	0 (0.0)	2 (4.5)	0.494	0 (0.0)	4 (14.3)	0.111
Length of ICU stay (days)	6.0 (4.0–8.0)	<0.001	<0.001	6.0 (4.0–8.0)	8.0 (5.0–11.0)	0.210	5.0 (4.0–8.0)	9.5 (5.3–17.0)	0.030
Mortality	0 (0.0)	0.001	<0.001	0 (0.0)	4 (9.1)	0.116	0 (0.0)	11 (39.3)	<0.001

Notes: Data were presented as n (%) and median (interquartile range). Group N-N was composed of T2DM patients treated without insulin before and after ICU admission. Group N-I was composed of patients who received treatment without insulin before ICU admission but received insulin treatment after ICU admission, which also referred to preadmission non-insulin treated T2DM patients. Group I-I was composed of patients who received insulin treatment before and after ICU admission, which also referred to preadmission insulin-treated T2DM patients. ^‡And ^§Age ± 10 years, gender, blood glucose >10 mmol/L on admission, diabetic nephropathy, chronic kidney disease, coronary heart disease, sepsis, acute myocardial infarction on admission were used for matching.

Abbreviation: ICU, intensive care units.