Comparison of the Efficacy of Different Insulin Administration and Blood Glucose Monitoring Methods in the Treatment of Type 1 Diabetes Mellitus in Children.

Objective: To compare the clinical efficacy of different insulin administration methods and blood glucose monitoring methods in treating type 1 diabetes mellitus in children.
Methods: Patients were divided into four groups: multiple daily injection (MDI) + fingertip blood glucose detection, continuous subcutaneous insulin infusion (CSII) + fingertip blood glucose detection, MDI + continuous glucose monitoring system (CGMS), and CSII + CGMS. After six months of treatment, followed by telephone and at least once a month in an outpatient clinic, insulin doses were adjusted according to the children's blood glucose levels. Blood glucose control and the daily dose of insulin were compared among the four groups after treatment, and the incidence of hypoglycemia in each group was recorded during the treatment. We also compare the incidence of the adverse event among the four groups.
Results: 6 months later, the levels of HbA1c, FBG, and two h PG in each group were lower than those before treatment. There were significant differences in HbA1c, two h PG, and the daily insulin dose among the four groups. There were differences in the frequency of hypoglycemia among all the groups. The frequency of hypoglycemia in groups C and D was lower than in group A. Conclusions: CSII was better than MDI, and the blood glucose monitoring effect of CGMS was better than the fingertip blood glucose detection. The patients treated with CSII combined with CGMS had the best clinical efficacy. The patients treated with CSII combined with CGMS had the lowest adverse events incidence.

1. Introduction

Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by T lymphocyte-mediated directed destruction of islet β cells, which leads to absolute insufficiency of insulin secretion and disorders of glucose, lipid, and protein metabolism [1, 2]. Epidemiological studies have shown that the incidence of T1DM is increasing year-by-year globally, with a trend of younger age [3], and the annual growth rate of T1DM in children <5 years old is 3–4% [4]. Due to poor compliance in children, blood sugar management is significantly different from that of adults. The incidence of T1DM in China is 2/100,000 ∼ 5/100,000, with an increase of about 6,000 cases per year [5, 6]. T1DM cannot be cured completely. Once diagnosed, children need to control their diet, monitor blood glucose, and rely on insulin therapy for life. T1DM has become a chronic lifelong metabolic disease that seriously threatens the health of children and adolescents. Therefore, strengthening the diagnosis, treatment, and long-term care of children with type I diabetes in China is of positive significance.

Children with T1DM are in the continuous growth stage, and insulin might not fully meet the growth needs, so blood glucose is relatively difficult to control. With the acceleration of growth in puberty, the change of secretory hormone is more evident and complex, further interfering with the pancreas. The effect of insulin makes it particularly difficult to control blood glucose during this period. There are two commonly used treatment methods for T1DM in children. One is multiple daily injections (MDI). The other simulates physiological insulin secretion through continuous subcutaneous insulin infusion (CSII), also called an insulin pump. In less developed countries, MDI is frequently used in T1DM to heal children. Nevertheless, there existed several problems in best blood glucose control because children's compliance with MDI is poorer than that of adults; thus, just a minor quantity of sufferers complete the blood glucose aims by MDI. As a substitute for treating MDI, CSII is the most extraordinary insulin remedy in China, more intimately imitating insulin exudation and is described to reach a considerably lesser hazard of hypoglycemic occurrence without diabetic ketoacidosis [7]. In addition to insulin injection, monitoring blood glucose stability to guide treatment is also crucial. Commonly used blood glucose monitoring methods in clinical practice include the measurement of blood glucose on fingertip by the trace glucose meter and continuous glucose monitoring system (CGMS). The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the tremendous clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes [8].

This study retrospectively analyzed the clinical treatment practices of our hospital from May 2018 to October 2020 and compared the effects of different insulin administration methods and blood glucose monitoring methods on the clinical efficacy of children.

2. Materials and Methods

2.1. Research Subjects

This study was a retrospective study, and 134 children with T1DM treated in our hospital's Department of Endocrinology and Rheumatology from May 2018 to October 2020 were selected as the subjects. They were divided into four groups according to insulin administration and blood glucose monitoring methods: group A : MDI + fingertip blood glucose detection; group B : CSII + fingertip blood glucose test; group C : MDI + CGMS; and group D : CSII + CGMS. The inclusion criteria include the following: (1) patients with age <18; (2) patients who met the diagnostic criteria of T1DM in Chinese Guidelines for Diagnosis and Treatment of Type 1 Diabetes Mellitus [9]; (3) patients who met the diagnostic criteria of T1DM by the WTO and American Diabetes Association [10]; (4) patients with perfect clinical data; and (5) patients with their families signed written informed consent. The exclusion criteria include the following: (1) patients with other types of diabetes; (2) patients with a course of disease less than one year; (3) patients with acute or chronic complications of diabetes requiring emergency treatment; (4) patients complicated with the insufficiency of other vital organs (liver and kidney); (5) patients were taking or recently taking drugs that affect insulin sensitivity and hypoglycemic drugs; and (6) patients in a state of disease stress. The Medical Ethics Committee approved this study of Anhui Children's Hospital.

2.2. Methods

2.2.1. Data Collection

General data, such as gender, age, height, weight, course of diabetes, HbA1c level, fasting blood glucose level, liver function, and kidney function, were collected through Anhui Children's Hospital's electronic medical record system, the BMI of patients was calculated.

2.2.2. Therapeutic Methods

All the children received routine treatment, including fluid rehydration treatment, electrolyte balance, acid-base balance, diet control, and strengthening exercise, based on which the insulin therapy was given. The children in groups A and C were given multiple subcutaneous injections, with the total insulin dosage being 0.5∼1 U/(kg·d). Gansulin 30R (SFDA approval number: S20020092) was injected subcutaneously within half an hour before meals. Gansulin N (SFDA approval number: S20020091) was injected subcutaneously before bedtime. The children in groups B and D were injected with the insulin pump. Fornia insulin pump was selected. The needle was connected to the insulin pump through a continuous catheter, and the needle was subcutaneously implanted for 24 h continuous infusion of Gansulin R. The total amount of insulin was 0.5–1 U/(kg·d), 50% of the total daily amount of insulin as the necessary amount, and the remaining 50% as the additional amount based on the feeding situation and blood glucose level of the children. The treatment was pumped within half an hour before meals. Children and their families were taught how to change the insulin pipeline, set large, essential, and large supplemental doses, dispose of various alarms, and suspend the insulin pump. In groups A and B, a blood glucose monitor was used to extract blood from fingertips to measure the blood glucose level, and insulin usage was adjusted according to the blood glucose level. Group C and D were a dynamic blood glucose monitoring system (Medtronic dynamic blood glucose monitor), which closely monitored the continuous blood glucose changes of the children and adjusted the use of insulin according to the blood glucose level.

2.3. Follow-Up and Observation Indicators

All the children were treated for over half a year, followed by telephone and outpatient. All the children underwent various examinations, including HbA1c, fasting blood glucose, liver function, and kidney function, at least once a month in the outpatient department, and the insulin dose was adjusted according to the blood glucose level. Blood glucose control, including fasting blood glucose level, two h postprandial blood glucose level, and HbA1c level, was compared between the four groups after six months of treatment. The daily insulin dose was recorded six months after treatment, and the incidence of hypoglycemia during treatment was recorded. According to the diabetes guidelines updated by the American Diabetes Association in 2020, diabetic patients with blood glucose <3.9 mmol/L are considered hypoglycemia [11].

2.4. Statistical Analysis

SPSS 22.0 software was used for statistical analysis. Counting data were expressed in n (%), and the χ2 test was used to compare the groups. Measuring data conformed to the normal distribution were expressed in ( ± s), and a comparison between the two groups was performed using a t-test of independent samples while that between the three groups using one-way ANOVA. P < 0.05 meant significant difference.

3. Results

3.1. Comparison of General Data

In total, 134 study participants were enrolled in this research. No statistical significance was observed in both the groups' age, gender, and BMI (p > 0.05), as shown in Table 1. In addition, no statistically significant differences were observed among the four groups in the diabetes course, HbA1c, fasting blood glucose, and two h postprandial blood glucose all P < 0.05. Specific data are shown in Table 2.

Table 1

General clinical data of the study participants.

Groups	Group A (n = 28)	Group B (n = 36)	Group C (n = 34)	Group D (n = 36)	F	P
Gender (male/female)	19/9	25/11	22/12	24/12	0.188	0.979
Age (y)	7.26 ± 2.41	7.31 ± 2.16	6.74 ± 2.48	7.15 ± 2.71	1.752	0.160
Weight (kg)	15.45 ± 2.48	16.73 ± 3.29	16.53 ± 2.60	15.42 ± 3.04	0.462	0.324
Height (cm)	70.23 ± 10.02	64.03 ± 5.15	62.78 ± 4.98	65.46 ± 6.99	1.237	0.389
BMI (kg/m2)	18.45 ± 1.40	18.68 ± 1.27	18.59 ± 1.65	18.82 ± 1.34	0.168	0.918

Note: compared with group A, P < 0.05 and P < 0.01; compared with group B, #P < 0.05 and ##P < 0.01; and compared with group C, &P < 0.05 and &&P < 0.01.

Table 2

Comparison of general clinical data of the four groups of children.

Groups	Group A (n = 28)	Group B (n = 36)	Group C (n = 34)	Group D (n = 36)	F	P
The course of the disease (y)	3.14 ± 1.05	4.33 ± 2.07	4.06 ± 0.29	3.57 ± 1.13	1.277	0.285
HbA1c (%)	8.86 ± 2.19	8.75 ± 1.96	8.58 ± 1.86	8.96 ± 1.61	0.225	0.879
Fasting blood glucose (mmol/l)	7.78 ± 3.21	7.69 ± 3.25	7.84 ± 3.26	7.74 ± 3.37	0.468	0.705
2 h postprandial blood glucose (mmol/l)	14.25 ± 1.29	14.13 ± 1.23	14.37 ± 1.16	14.43 ± 1.30	0.677	0.568

Note: compared with group A, P < 0.05 and P < 0.01; compared with group B, #P < 0.05 and ##P < 0.01; and compared with group C, &P < 0.05 and &&P < 0.01.

3.2. Comparison of Blood Glucose Control and Daily Insulin Dosage in the Four Groups after Treatment

After half a year of treatment, HbA1c, fasting blood glucose, and two h postprandial blood glucose levels in each group were lower than before. There were significant differences in HbA1c, 2 h postprandial blood glucose, and daily insulin dosage among the four groups (P < 0.05, P < 0.01, and P < 0.05). Compared with group A, the HbA1c levels in group B and D were significantly lower (P < 0.01 and P < 0.05), the fasting blood glucose levels in group D was significantly lower (P < 0.05), and the 2 h postprandial blood glucose levels in groups B, C, and D were significantly lower (P < 0.05, P < 0.01, and P < 0.01); compared with group B, the HbA1c level in group C was significantly lower (P < 0.05), and the 2h postprandial blood glucose level in group D was significantly lower (P < 0.05); no significant differences were seen in blood glucose control and daily insulin dosage in other intergroup comparisons (all P > 0.05, Table 3).

Table 3

Comparison of blood glucose control and daily insulin dosage in the four groups after treatment.

Groups	Group A (n = 28)	Group B (n = 36)	Group C (n = 34)	Group D (n = 36)	F	P
HbA1c (%)	8.22 ± 2.14	7.72 ± 1.42∗∗	8.06 ± 1.64#	7.61 ± 1.35∗	3.610	0.015
Fasting blood glucose (mmol/l)	7.04 ± 1.25	6.39 ± 1.22	6.25 ± 1.32	6.07 ± 1.14∗	1.445	0.233
2 h postprandial blood glucose (mmol/l)	10.15 ± 1.46	9.96 ± 1.58∗	9.67 ± 2.19∗∗	8.21 ± 1.63∗∗#	7.507	0.000
Daily insulin dosage	0.76 ± 0.11	0.68 ± 0.24	0.70 ± 0.16∗	0.65 ± 0.12∗∗	3.823	0.012

Note: compared with group A, P < 0.05 and P < 0.01; compared with group B, #P < 0.05 and ##P < 0.01; and compared with group C, &P < 0.05 and &&P < 0.01.

3.3. Comparison of Hypoglycemia Incidence among the Four Groups during the Follow-Up

During the treatment, 23 patients in group A, 25 in group B, 26 in group C, and 21 in group D had hypoglycemia, with 82.14%, 69.44%, 76.47%, and 58.33%, respectively. No significant differences were seen between the four groups (P > 0.05) and between every two groups, all P > 0.05. However, the differences in the frequency of hypoglycemia among the groups were statistically significant (P < 0.01). Compared with group A, the frequency of hypoglycemia in groups C and D was markedly lower (P < 0.05 and P < 0.01), while no significant differences were observed between the other in-pair comparisons (all P > 0.05, Table 4).

Table 4

Comparison of hypoglycemia incidence among the four groups during the follow-up.

Groups	Group A (n = 28)	Group B (n = 36)	Group C (n = 34)	Group D (n = 36)	F	P
The number of cases with hypoglycemia	23 (82.14)	25 (69.44)	26 (76.47)	21 (58.33)	0.142	0.085
The number of cases without hypoglycemia	5 (17.86)	11 (30.56)	8 (23.53)	14 (41.66)
Frequency of hypoglycemia	2.28 ± 1.09	1.75 ± 1.31	2.04 ± 1.27∗	1.42 ± 1.36∗∗	4.146	0.008

Note: compared with group A, P < 0.05 and P < 0.01; compared with group B, #P < 0.05 and ##P < 0.01; and compared with group C, &P < 0.05 and &&P < 0.01.

3.4. Comparison of Adverse Events Incidence among the Four Groups during the Follow-Up

Five episodes of diabetic ketoacidosis in group A, three episodes of diabetic ketoacidosis in group B, two episodes of diabetic ketoacidosis in group C, and only one episode of diabetic ketoacidosis in group D were reported. Of 16 episodes of severe hypoglycemia reported, 7 cases were related to the MDI + fingertip blood glucose detection group, 4 cases were related to the CSII + fingertip blood glucose test group, 3 cases were related to the MDI + CGMS group, and 2 cases were related to the MDI + CGMS group, and 1 case was related to CSII + CGMS. Moreover, five episodes of site infections in group A, three episodes in group B, three episodes in group C, and only one episode of site infections in group D were reported. Of 10 episodes of pump failure reported, 4 cases were related to the MDI + fingertip blood glucose detection group, 3 cases were related to the CSII + fingertip blood glucose test group, 1 case was related to the MDI + CGMS group, and 2 cases were related to the MDI + CGMS group, and 1 case was related to CSII + CGMS (Table 5).

Table 5

Comparison of adverse events incidence among the four groups.

Groups	Group A (n = 28)	Group B (n = 36)	Group C (n = 34)	Group D (n = 36)	F	P
Diabetic ketoacidosis	5	3	2	1	1.249	0.112
Severe hypoglycemia	7	4	3	2	2.334	0.056
Site infections	5	3	3	1	1.002	0.395
Insulin administration error	3	2	1	1	1.337	0.150
Pump failure	4	3	1	2	2.003	0.127

Note: compared with group A, P < 0.05 and P < 0.01; compared with group B, #P < 0.05 and ##P < 0.01; and compared with group C, &P < 0.05 and &&P < 0.01.

4. Discussion

T1DM is a chronic disease that seriously threatens the health of children and adolescents. Without timely intervention, it will lead to various complications in children. Children with T1DM must use insulin regularly and need effective blood glucose monitoring due to their young age, difficult diet control, fast physical growth, and a lot of exercises [12]. At present, various glucose-reducing regimens emerge in endlessly. This study retrospectively analyzed the four commonly used hypoglycemic regimens in clinical practice in our hospital and compared the therapeutic effects of different glucose-reducing regimens.

CSII is an effective way to treat T1DM by simulating the insulin secretion function of the human body to control blood glucose stability. Studies have found that CSII can better control blood glucose than MDI [13]. HbA1c is an essential indicator for evaluating blood glucose control and predicting the occurrence and development of chronic complications of diabetes, and it can effectively reflect the average blood glucose level in 2∼3 months [14]. In the present study, the HbA1c level was markedly lower in groups B and D than in group A, indicating the insulin pump's relatively good hypoglycemic effect. Clinical data at home and abroad show that CSII can reduce the insulin dosage. Szypowska et al. [15] found that the insulin dosage used by CSII patients is lower than that of patients receiving MDI treatment. Wang et al. [16] found that the amount of insulin can be effectively reduced after CSII treatment in children with T1DM in Qingdao. In the present study, the daily insulin dosage of groups B and D was lower than that of groups A and C after half a year of treatment, which was consistent with the literature research results, but the differences were not significant.

The benefit of MDI is that the blood glucose level could be rigorously measured by various and self-regulating dose modification; however, the repeated injection might be uncomfortable and disturb children's everyday living. CGMS is a novel blood glucose monitoring method. By monitoring the glucose level of interstitial fluid, it can reflect the blood glucose level and blood glucose fluctuation throughout the day, and it is easier to detect latent hypoglycemia and hyperglycemia [17, 18], which is conducive to personalize adjustment of the insulin dosage and controlling the stability of blood glucose [19]. Hypoglycemia is a major limiting factor for glycemic control in children with T1DM, so reducing the incidence of hypoglycemia is an integral part of glycemic management in T1DM [20]. In the present study, the 2h postprandial blood glucose level in group D was significantly lower than that in group B. The daily dose of insulin in group C was significantly lower than that in group A. During the treatment period, there were significant differences in the frequency of hypoglycemia among the four groups (P < 0.05), and the frequency of hypoglycemia in group C and D was significantly lower than that in group A (P < 0.05). This indicated that CGMS was more comprehensive and accurate in monitoring blood glucose levels than fingertip blood glucose monitoring. Moreover, CSII + CGMS could adjust the insulin dose according to the accurate blood glucose data to avoid blindness, which better controlled the stable blood glucose, reduced the dose of insulin use, and lowered the incidence of hypoglycemia. We also compared the incidence of adverse events among the four groups. The results suggested that the patients treated with CSII combined with CGMS had the lowest adverse event incidence. However, the objective of this study was to evaluate the efficacy of different insulin administration and blood glucose monitoring methods in treating type 1 diabetes mellitus in children, and the follow-up period is not long enough.

In conclusion, for the clinical treatment of children with T1DM, the therapeutic effect of CSII was better than that of MDI, and the therapeutic effect of CGMS was better than that of fingertip blood glucose monitoring. CSII combined with CGMS showed the best clinical efficacy.