Comparative effects of insulin pump and injection on gestational diabetes mellitus pregnancy outcomes and serum biomarkers

Abstract

BACKGROUND

Insulin injection is the basic daily drug treatment for diabetic patients.

AIM

To evaluate the comparative impacts of continuous subcutaneous insulin infusion (CSII).

METHODS

Based on the treatment modality received, the patients were allocated into two cohorts: The CSII group and the multiple daily injections (MDI) group, with each cohort comprising 210 patients. Comparative assessments were made regarding serum levels of serum-secreted frizzled-related protein 5, homocysteine, and C1q/TNF-related protein 9. Furthermore, outcomes such as fasting plasma glucose, 2-hour postprandial glucose levels, pain assessment scores, and the incidence of complications were evaluated post-treatment.

RESULTS

The CSII group displayed notably lower fasting plasma glucose and 2-h postprandial glucose levels in comparison to the MDI group (P < 0.05). Subsequent analysis post-treatment unveiled a significantly higher percentage of patients reporting no pain in the CSII group (60.00%) in contrast to the MDI group (36.19%) (P < 0.05). Additionally, the CSII group exhibited a markedly reduced occurrence of fetal distress and premature rupture of membranes compared to the MDI group (P < 0.05). However, there were no significant variances observed in other pregnancy outcomes between the two groups (P > 0.05). A statistical analysis revealed a significant difference in the incidence of complications between the groups (χ² = 11.631, P = 0.001).

CONCLUSION

The utilization of CSII via an insulin pump, as opposed to MDI, can significantly enhance the management of insulin administration in patients with GDM by diversifying the sites of insulin delivery. This approach not only promotes optimal glycemic control but also regulates metabolic factors linked to blood sugar, reducing the likelihood of adverse pregnancy outcomes and complications. The clinical relevance and importance of CSII in GDM management highlight its wide-ranging clinical usefulness.

Key Words: Continuous subcutaneous insulin infusion, Multiple daily injections, Gestational diabetes mellitus, Pregnancy outcome, Serum biomarkers

Core Tip: This study delineates the comparative efficacy of continuous subcutaneous insulin infusion (CSII) via insulin pumps and multiple daily injections in managing gestational diabetes mellitus (GDM), focusing on pregnancy outcomes and serum biomarkers. It reveals CSII's superior capability in enhancing glycemic control, reducing pain, and decreasing the incidence of fetal distress and premature rupture of membranes, without significantly altering other pregnancy outcomes. Highlighting the novel insight into CSII's role in modulating key metabolic biomarkers, this research contributes to optimizing GDM management strategies, offering a significant leap towards personalized diabetic care in pregnancy.

INTRODUCTION

Diabetes mellitus (DM) is a systemic metabolic disease characterized by hyperglycemia[1-4]. With the development of aging society, the number of diabetic gestational DM (GDM) patients is increasing, but their onset is insidious and difficult to detect[5,6]. Insulin injection is the basic daily drug treatment for diabetic patients[7-9]. It is usually injected subcutaneously at the relaxed part of the skin, and the injection site needs to be changed frequently to reduce pain and adverse reactions of patients. GDM refers to elevated blood sugar or decreased glucose tolerance first detected or occurring during pregnancy, which is a common complication of pregnancy[10,11]. Without effective management, GDM can lead to different degrees of adverse outcomes for mothers and infants. Insulin pump, also known as continuous subcutaneous insulin infusion device, is an insulin injection device controlled by artificial intelligence[12]. It is mainly connected to the human body through infusion pipes and needles buried under the skin to simulate the secretion of human pancreatic beta cells and continuously inject insulin to control blood sugar. The injection methods are divided into continuous basal insulin injection and pre-prandial insulin injection, which are used to control blood glucose at night, fasting, pre-prandial and postprandial respectively. Compared with subcutaneous injection, it has the advantages of faster standard, less blood sugar fluctuation and less insulin consumption[12]. It is commonly used to treat patients with poor blood sugar control, brittle diabetes, perioperative and gestational diabetes. This study aims to compare the effects of insulin pump and insulin subcutaneous injection on pregnancy outcome and serum secreted frizzled-related protein 5 (SFRP5), homocysteine (Hcy), and C1q/TNF-related protein 9 (CTRP9) in patients with GDM.

MATERIALS AND METHODS

General information

We retrospectively analyzed medical records of 420 patients with GDM who received treatment in our hospital from January 2020 to December 2022 and divided into insulin pump group and insulin subcutaneous injection group with 210 cases in each group based on different treatment methods. Inclusion criteria: (1) Meeting the World Health Organization diagnostic criteria for GDM; (2) Can accurately describe and express body feelings; (3) People aged 20-40 years old; (4) Patients diagnosed as needing long-term insulin injection; and (5) There were no adverse skin and limb conditions before joining the study. Exclusion criteria for patients: (1) Have language barriers difficult to communicate; (2) Patients with severe liver and kidney diseases; and (3) People unable to take care of themselves. This study was approved by the Ethics Committee of Xi'an Central Hospital. There was no significant difference between the two groups (P > 0.05; Table 1).

Table 1 Comparison of basic clinical data of two groups.

Group	n	Sex		Age (yr)	Course of disease (yr)	Educational background (n)
		Male	Female			Junior high school or below	High school	Above high school
Insulin pump group	210	114	96	32.65 ± 9.14	12.45 ± 2.16	50	88	72
Insulin subcutaneous injection group	210	110	100	33.01 ± 9.53	13.04 ± 2.58	46	90	74
Statistical value	-	0.085		0.395	2.541	0.9198
P value	-	0.770		0.693	0.011	0.6313

Treatment methods

The procedure of using insulin pump is as follows: First, choose the site of infusion and implantation, the abdomen is the first choice, followed by the upper arm, the outside of the thigh, the back and the buttocks, etc.; Second, to install the insulin pump, you should follow the instructions of the selected insulin pump, which usually include the following operating steps: Prepare medicines and materials, clean hands to prevent infection, extract insulin to fill the medicine storage device and remove bubbles, connect the infusion tube, install, fill and bury the subcutaneous input device, and turn on the insulin pump. If dynamic glucose monitoring is possible at the same time, the probe should be prepared and installed, and then the Continuous glucose monitoring should be turned on. After the initial 2 h, the blood glucose value of the finger should be injected for calibration.

The methods of insulin subcutaneous injection are as follows: (1) Self preparation, clean hands before injection, determine the time to eat, prepare insulin, prepare corresponding items, such as 75% medical alcohol and medical cotton swabs. (2) Select the injection site. The suitable sites for subcutaneous insulin injection are the abdomen, the outer thigh, the outer arm and the buttocks; (3) Install the needle, disinfect the rubber film at the front end of the pen lead with 75% alcohol, take out the special needle for insulin injection, open the package, tighten the needle clockwise, and the installation is completed; (4) Exhaust, adjust the dose, and then disinfect the skin, choose 75% alcohol or disinfection cotton tablets, such as alcohol volatilization after injection; and (5) The injection should be carried out subcutaneously to avoid entering the muscle layer. After the rapid injection, the thumb should press the injection key, slowly and evenly inject the liquid, and then the needle should be pulled out to press the injection site, and the eye of the needle should be pressed with a dry cotton swab for more than 30 s.

Sample collection and quantitative analysis

The 5 mL fasting venous blood was collected from all pregnant women, the serum was separated after standing, and then sent to the laboratory for detection of fasting serum SFRP5, Hcy, and CTRP9 Levels. The detection instrument was automatic biochemical analyzer (Beckmann AU5800), and the kit was Beckmann's original kit. The operation was completed by laboratory physicians with inspection qualifications and rich detection experience.

Efficacy evaluation criteria

All patients were evaluated after 50 injections. After treatment, fasting blood glucose and 2 h postprandial blood glucose of the two groups were measured respectively. The fasting blood glucose was 5.0 to 7.0 mmol/L, and the postprandial blood glucose was 5.0 to 10.0 mmol/L. Before the study, all patients were informed of the pain criteria, that is, 0 score for no pain at all, 1 score for mild pain, 2 score for moderate pain, 3 score for severe pain, and 4 score for unbearable pain. After treatment, all patients were given pain score statistics. The complications such as skin swelling, muscle atrophy and subcutaneous hard mass were analyzed and compared between the two groups.

Statistical analysis

SPSS 19.0 statistical software was used to analyze all the data. Continuous variables are expressed as mean ± SD. Independent sample t test was used to compare the measurement data between the insulin pump group and the insulin subcutaneous injection group. The count data was expressed as rate (%) and Chi-square test was used. P < 0.05 meant the difference was statistically significant.

RESULTS

Comparison of blood glucose in two groups after treatment

After treatment, blood glucose tests were carried out in the two groups to determine fasting and 2 h postprandial blood glucose respectively, as shown in Table 2. The results showed that the fasting blood glucose levels and 2-h postprandial blood glucose levels in the insulin pump group were 5.67 ± 1.58 and 8.41 ± 1.27, respectively, while the fasting blood glucose levels and 2-h postprandial blood glucose levels in the insulin subcutaneous injection group were 6.58 ± 1.07 and 9.35 ± 1.59, respectively. Therefore, the fasting blood glucose and 2 h postprandial blood glucose in the insulin pump group were significantly lower than those in the subcutaneous insulin injection group, and the data difference between the two groups was statistically significant (P < 0.05).

Table 2 Comparison of levels of blood sugar after treatment in two groups of patients.

Group	n	Fasting blood glucose	2 h postprandial blood glucose
Insulin pump group	210	5.67 ± 1.58	8.41 ± 1.27
Insulin subcutaneous injection group	210	6.58 ± 1.07	9.35 ± 1.59
Statistical value	-	6.910	6.694
P value	-	< 0.001	< 0.001

Comparison of pain after injection between the two groups

After treatment, all patients were asked to score their pain, as shown in Table 3. Our study found that the number of painless patients in the insulin pump group accounted for 60.00% (126/210), significantly higher than 36.19% (76/210) in the insulin subcutaneous injection group, and the difference in the number of painless patients between the two groups was statistically significant (P < 0.05). A total of 40 patients with pain scores of 2 or above in the insulin pump group and 56 patients in the subcutaneous injection group had statistical significance between the two groups (P < 0.05).

Table 3 Comparison of pain scores of two groups.

Group	n	0	1	2	3	4
Insulin pump group	210	126	44	34	6	0
Insulin subcutaneous injection group	210	76	78	42	12	2
Statistical value	-	23.844
P value	-	< 0.001

Comparison of pregnancy complications and pregnancy outcomes between the two groups

This section of the experiment compared the pregnancy complications and pregnancy outcomes of two groups of subjects. The results showed that there were 2 cases of premature rupture of embryos in the insulin pump group, while there were 26 cases of premature rupture of embryos in the insulin subcutaneous injection group. The difference between the two is significant and statistically significant (P < 0.05). Meanwhile, the results showed that there were 2 cases of fetal distress in the insulin pump group, while there were 16 cases of premature rupture of embryos in the insulin subcutaneous injection group. The difference between the two is significant and statistically significant (P < 0.05). In addition, there was no statistically significant difference in pregnancy outcomes between the two groups of patients, including amniotic fluid contamination, oligohydramnios, preeclampsia, and macrosomia (P > 0.05; Table 4).

Table 4 Comparison of pregnancy complications and pregnancy outcomes between the two groups.

Group	n	Amniotic fluid contamination	Oligohydramnios	Preeclampsia	Premature rupture of membranes	Macrosomia	Fetal distress
Insulin pump group	210	8	6	6	2	2	2
Insulin subcutaneous injection group	210	14	10	8	26	4	16
Statistical value	-	1.727	1.04	0.296	22.041	0.676	11.376
P value	-	0.189	0.308	0.586	< 0.001	0.411	0.001

Comparison of complications between the two groups

The incidence of complications in the two groups was analyzed, including skin redness, muscle atrophy, subcutaneous hard mass. The results showed that in the insulin pump group, there were 2 case of skin redness and swelling, 4 cases of subcutaneous hard mass, a total of 6 cases, accounting for 2.86%. In the subcutaneous injection group, there were 8 cases of skin redness, 6 cases of muscle atrophy and 10 cases of subcutaneous hard mass, accounting for a total of 24 cases (11.43%). The incidence of complications was statistically significant between the two groups (χ² = 11.631, P = 0.001).

Comparison of SFRP5, Hcy, and CTRP9 Levels between the two groups

This section compares the levels of SFRP5, Hcy, and CTRP9 between two groups of patients. The results showed that the levels of SFRP5 and CTRP9 in the insulin pump group were 6.72 ± 1.05 mmol/L and 46.28 ± 8.15 mmol/L, respectively, while the levels of SFRP5 and CTRP9 in the insulin subcutaneous injection group were 6.08 ± 1.26 and 38.86 ± 6.54 mmol/L, respectively, with significant differences and statistical significance (P < 0.05). In addition, the Hcy level in the insulin pump group was 5.27 ± 2.02 mmol/L, while the Hcy level in the insulin subcutaneous injection group was 7.04 ± 1.48 mmol/L, with a significant and statistically significant difference between the two groups (P < 0.05; Table 5).

Table 5 Comparison of levels of insulin pump group, subcutaneous injection group, secreted frizzled-related protein 5, homocysteine and C1q/TNF-related protein 9.

Variable	Insulin pump group (n = 210)	Insulin subcutaneous injection group (n = 210)	t/χ2	P value
SFRP5 (mmol/L)	6.72 ± 1.05	6.08 ± 1.26	5.655	< 0.001
Hcy (mmol/L)	5.27 ± 2.02	7.04 ± 1.48	10.243	< 0.001
CTRP9 (mmol/L)	46.28 ± 8.15	38.86 ± 6.54	10.290	< 0.001

Hcy: Homocysteine; SFRP5: Secreted frizzled-related protein 5; CTRP9: C1q/TNF-related protein 9.

DISCUSSION

At present, insulin injection is one of the commonly used and effective means for daily treatment of diabetes patients[7]. Clinical research results have shown that compared to subcutaneous injection of insulin, the use of insulin pumping can more effectively and stably control the blood glucose levels of patients with diabetes[13-15]. Our above research results show that the fasting blood glucose and 2-h postprandial blood glucose levels in the insulin pump group after treatment are significantly lower than those in the subcutaneous insulin injection group, which further indicates that the injection method used in the insulin pump group can significantly alleviate and further alleviate the pain caused by subcutaneous insulin injection. Meanwhile, our research findings also indicate that the use of insulin pumps can reduce pain caused by multiple frequent injections of the same site, and has better practicality compared to randomly rotating the site. Once again, our research results have also confirmed that the positioning ruler can really help pregnant women with diabetes remember the injection site and assist in insulin injection for treatment. In addition, Statistics of the complications of the two groups showed that the complication rate of the insulin pump group was lower, only 5.00%, which was significantly lower than the 20.00% of the insulin subcutaneous injection group. This is inseparable from the fact that the positioning ruler can effectively help the elderly to carry out injections in different parts, which can effectively relieve the adverse reactions such as skin redness and swelling, subcutaneous hard lumps and reduce the occurrence of complications in patients.

Clinical research results show that Hcy is a specific indicator of vascular endothelial damage in vivo, and its level rise is closely related to the occurrence and development of diabetes in pregnancy[16-18]. Hcy, as a metabolite of methionine and cysteine, can produce reactive oxidants, promote the production of hydrogen peroxide and oxygen free radicals, and thus damage the vascular wall. It is a multifunctional injury factor[19]. Meanwhile, studies have shown that the metabolism of this multifunctional loss factor in vivo is mainly through the extracellular fluid pathway, participating in the folate methionine cycle, etc[20]. In addition, clinical studies have shown that Hcy can promote the proliferation of vascular smooth muscle cells, causing endothelial abnormalities, microfiber loss and aggregation disorders, leading to thickening of vascular walls, decreased vasodilation ability, increased blood circulation resistance, elevated blood pressure, impaired endothelial cell function, and exacerbating vascular damage caused by hyperlipidemia through various pathways[21]. It leads to the increase of incidence rate of diabetes in pregnancy. Therefore, it is of high clinical value and significance to measure the serum Hcy level of pregnant women with diabetes.

SFRP5 is a novel anti-inflammatory adipokine, which belongs to the SFRP family[22,23]. Because SRRP5 can competitively bind to the Wnt5a protein, inhibit the Wnt signaling pathway, and inhibit the activation of key inflammatory cells (mainly macrophages in adipose tissue), reducing the secretion of inflammatory cytokines[24]. SFRP5 acts as a link between obesity and other metabolic diseases. In-depth study of the interaction between the transduction molecules in the SFRP5 and Wnt signaling pathways may open up new opportunities to develop treatments for obesity-related metabolic diseases. Some studies have mentioned that CTRP9 plays an important role in glucose metabolism in rats, and is closely related to obesity and T2DM, but the specific mechanism is still unclear[25]. Other studies have shown that abnormally elevated levels can improve insulin resistance and significantly lower serum insulin levels[26]. In our study, the levels of SFRP5 and CTRP9 in the insulin pump group were 6.72 ± 1.05 mmol/L and 46.28 ± 8.15 mmol/L, respectively, while the levels of SFRP5 and CTRP9 in the insulin subcutaneous injection group were 6.08 ± 1.26 and 38.86 ± 6.54 mmol/L, respectively, with significant differences and statistical significance (P < 0.05). This result suggests that the level of SFRP5 and CTRP9 in patients with gestational diabetes can be effectively increased by means of insulin pumping.

CONCLUSION

To sum up, compared with subcutaneous injection of insulin, the insulin pumping method can effectively assist pregnant women with diabetes to release insulin at different parts of the body, disperse the drug delivery sites, and effectively control the blood sugar level of the patients. In addition, this method can effectively regulate the blood glucose related metabolic factors in the patient's body to a certain extent, thereby reducing the incidence of complications. Therefore, this method has high clinical application value.