Neutral protamine hagedorn/regular insulin in the treatment of inpatient hyperglycemia: Comparison of 3 basal-bolus regimens

Table 1 Baseline clinical characteristics

	NPH × 1	NPH × 2	NPH × 3	P
n	30	40	35
Age (yr, X ± DS)	60 ± 15	58 ± 15	54 ± 14	0.39
Gender (% female)	12 (40)	20 (50)	22 (63)	0.18
Unknown history of T2DM, n (%)	12 (40.0)	4 (10.0)	4 (11.4)	0.01
Duration of T2DM (yr), med (min-max)	5 (0-30)	15 (0-30)	10 (0-25)	0.01
Prior T2DM therapy, n (%)				0.02
None	17 (56.7)	7 (17.5)	9 (25.7)
Oral antidiabetics	9 (30.0)	20 (50.0)	15 (42.9)
Insulin	4 (13.3)	21 (52.5)	15 (42.9)
Insulin + oral antidiabetics	-	8 (20.0)	4 (11.4)
Charlson score, med (min-max)	3 (1-9)	3 (1-5)	3 (1-7)	0.14
Hospitalization diagnosis, n (%)
Coronary artery disease	7 (23.3)	13 (32.5)	11 (31.4)	0.69
Infectious disease	5 (16.7)	13 (32.5)	9 (25.7)	0.35
Neoplasm	7 (23.3)	3 (7.5)	2 (5.7)	0.051
Dysrhythmias	4 (13.3)	1 (2.5)	2 (5.7)	0.23
Gastrointestinal hemorrhage	4 (13.3)	1 (2.5)	3 (8.6)	0.24
Pancreatitis	2 (6.7)	1 (2.5)	1 (2.9)	0.68
Stroke	-	2 (5.0)	1 (2.9)	0.78
Other	1 (3.3)	6 (15.0)	6 (15.0)	0.88
Hypertension, n (%)	8 (26.7)	12 (31.6)	15 (42.9)	0.33
Body mass index (kg/m2), X ± DS	26.4 ± 5.2	27.5 ± 5.6	27.5 ± 5.3	0.65
HbA1c (%), X ± DS	9.5 ± 2.4	10.2 ± 2.4	10.4 ± 2.8	0.45
HbA1c (mmol/mol)	80 ± 26	88 ± 26	90 ± 30
Admission blood glucose (mg/dL), X ± DS	272 ± 84	308 ± 62	306 ± 70	0.08
Glomerular filtration rate1 (mL/min), X ± DS	77.3 ± 32.9	86.9 ± 30.1	92.4 ± 23.4	0.13
Treatment follow-up (d), med (min-max)	6 (2-14)	6 (2-14)	7 (2-14)	0.41
Hospital stay (d), med (min-max)	8 (4-31)	8 (2-28)	10 (4-36)	0.39

¹Calculated with Chronic Kidney Disease Epidemiology Collaboration. T2DM: Type 2 diabetes mellitus; HbA1c: Glycosylated hemoglobin.

Table 2 Glycemic control and insulin dose¹

	NPH × 1, n = 30	NPH × 2, n = 40	NPH × 3, n = 35	P
Mean glucose (mg/dL)	160.3 ± 36.4	190.4 ± 48.0	178.7 ± 44.2	0.02
Fasting glucose (mg/dL)	149.2 ± 36.5	175.9 ± 54.6	169.5 ± 43.2	0.054
Random glucose (mg/dL)	164.4 ± 38.2	198.9 ± 53.2	181.0 ± 47.8	0.013
Glycemic control (%)	58.3 ± 25.3	42.4 ± 24.3	48.9 ± 24.1	0.031
Fasting glucose (%)	47.0 ± 35.0	34.0 ± 30.8	42.5 ± 32.3	0.253
Random glucose (%)	62.8 ± 25.9	45.5 ± 25.2	52.8 ± 26.6	0.024
50% daily glucoses within target range (%)	53.0 ± 29.4	43.8 ± 29.5	48.1 ± 30.6	0.455
Time to achieve 50% of daily glucoses within target range (h)	48.9 ± 27.8	61.2 ± 33.9	59.6 ± 47.0	0.438
75% daily glucoses within target range (%)	27.4 ± 26.5	14.3 ± 21.1	21.8 ± 25.5	0.069
Time to achieve 75% of daily glucoses within target range (h)	76.8 ± 48.4	84.8 ± 57.3	99.8 ± 85.1	0.904
Insulin dose (UI/kg)
Basal	0.44 ± 0.13	0.51 ± 0.18	0.52 ± 0.15	0.1
At discharge	0.48 ± 0.14	0.69 ± 0.28	0.65 ± 0.20	< 0.001
Δ Insulin dose	0.04 ± 0.10	0.19 ± 0.22	0.13 ± 0.18	0.004

¹Data are expressed as X ± SD.

Table 3 Glycemic control among subgroups

	NPH × 1, n = 30, (%)	NPH × 2, n = 40, (%)	NPH × 3, n = 35, (%)	P
DM ≤ 10 yr
Overall	62.1 ± 24.8	47.3 ± 25.6	50.4 ± 23.4	0.17
Fasting glucose	53.7 ± 31.9	35.2 ± 30.5	42.1 ± 32.0	0.03
Random glucose	65.9 ± 24.9	51.1 ± 27.2	55.8 ± 28.2	0.25
Pre-hospital insulin
Overall	77.5 ± 12.4	37.6 ± 23.9	37.7 ± 26.1	0.012
Fasting glucose	39.5 ± 35.5	29.7 ± 27.5	24.1 ± 25.1	0.59
Random glucose	91.8 ± 7.5	41.0 ± 26.1	46.0 ± 31.2	0.01
Baseline glucose > 300 mg/dL
Overall	52.9 ± 24.5	37.7 ± 26.9	40.8 ± 20.0	0.36
Fasting glucose	38.1 ± 35.6	33.6 ± 34.8	36.0 ± 26.7	0.94
Random glucose	57.4 ± 22.4	38.7 ± 26.1	42.7 ± 22.5	0.21
HbA1c > 9% (75 mmol/mol)
Overall	55.2 ± 24.0	33.7 ± 22.6	45.8 ± 28.1	0.06
Fasting glucose	43.0 ± 33.9	25.5 ± 27.3	40.4 ± 31.0	0.18
Random glucose	60.0 ± 22.3	36.6 ± 23.1	48.2 ± 28.3	0.04
Absence of infectious disease
Overall	61.0 ± 24.1	39.8 ± 25.1	50.9 ± 25.6	0.01
Fasting glucose	50.8 ± 34.0	34.2 ± 32.8	44.1 ± 35.8	0.22
Random glucose	65.4 ± 25.4	41.8 ± 25.3	54.3 ± 26.5	0.01
Glomerular filtration rate < 60 mL/min
Overall	62.8 ± 25.3	42.0 ± 29.7	45.2 ± 16.7	0.20
Fasting glucose	40.0 ± 34.7	35.1 ± 32.8	31.2 ± 20.3	0.87
Random glucose	71.9 ± 27.3	44.4 ± 30.4	55.4 ± 29.5	0.14
Body mass index, dex ± 29.52
Overall	63.4 ± 22.8	44.1 ± 25.2	48.0 ± 23.3	0.03
Fasting glucose	47.1 ± 35.0	39.9 ± 34.0	42.1 ± 30.4	0.78
Random glucose	69.9 ± 23.1	45.6 ± 25.1	50.8 ± 23.9	0.01

Proportion of patients that achieved glycemic targets during the whole follow up. Data are expressed as X ± SD. DM: Diabetes mellitus; HbA1c: Glycosylated hemoglobin.

Table 4 Rate of hypoglycemia among the study groups during the hospitalization

	NPH × 1, n = 30	NPH × 2, n = 40	NPH × 3, n = 35	P
Hypoglycemic events (n)	13	8	16
Severe hypoglycemia	–	1	–	0.45
Rate of hypoglycemia (%), (X ± SD)1	2.0 ± 3.8	0.7 ± 2.3	1.2 ± 3.1	0.21
Time to the first episode (d), (X ± SD)	6.2 ± 4.0	7.1 ± 1.2	8.2 ± 1.2	0.14
Insulin dose at event (IU/kg), (X ± SD)	0.38 ± 0.13	0.67 ± 0.17	0.94 ± 0.48	< 0.001
Time of presentation, n (%)
Before breakfast	5 (38.5)	2 (25.0)	1 (6.2)	0.11
Before supper	3 (23.1)	3 (37.5)	2 (12.5)	0.37
Before dinner	2 (15.4)	–	7 (43.8)	0.04
Bedtime	3 (23.1)	3 (37.5)	6 (37.5)	0.43

¹Data are expressed as proportion of events/total glucoses.