Influence of nutritional intervention on children with type 1 diabetes mellitus and DPP-4 in serum.

The level of dipeptidyl peptidase-4 (DPP-4) of children with type 1 diabetes mellitus (T1DM) was observed to evaluate the improvement in function of the nutritional intervention. In total, 132 children with T1DM (T1DM group) and 132 healthy children (NC group) based on physical examination admitted to our hospital from September 2014 to June 2015 and were studied. General data of the two groups as well as the concentration of DPP-4 and various biochemical criterion in peripheral serum were collected and analyzed. Compared with NC group, DPP-4 level of T1DM group was obviously increased (P<0.05); after insulin treatment, the serum level of DPP-4 of T1DM group decreased, but was still significantly higher than that of NC group (P<0.05). After 3 months of clinical nutritional intervention, body mass index (BMI) of children with T1DM was significantly reduced compared with data before the treatment (P<0.05). However, the level of DPP-4 appeared unchanged (P>0.05). Pearson's correlation analysis showed that the level of DPP-4 had a positive correlation with diabetic duration, BMI and gamma (γ)-glutamyl transpeptidase for children suffering TIDM (P<0.05). Multiple linear regression analysis showed that BMI may be a factor influencing DPP-4 level in serum of T1DM children. In conclusion, the level of DPP-4 in serum increased, and insulin treatment was able to decrease DPP-4 level in T1DM children. However, clinical nutritional intervention could not improve the level of DPP-4 and BMI may be an influental factor of the DPP-4 level.

Introduction

Type 1 diabetes mellitus (T1DM) of children is a congenital and chronical metabolic disease, which is caused by the absolute shortage of insulin secretion. All patients with T1DM depend on insulin treatment. Unfortunately, the treatment that is not on time may cause the death of child patients (1,2). Dipeptidyl peptidase-4 (DPP-4) is a kind of biology active enzyme, and the substrate glucagon-like peptide-1 (GLP-1) which actes by DPP-4 has the function of regulating blood sugar in human body (3,4). In clinic, DPP-4 inhibitor is often applied to cure T2DM, but the research on T1DM is, however, sparse (5–8). Therefore, based on previous studies, our study compared DPP-4 level in healthy children and those suffering T1DM before and after insulin treatment, under clinical nutritional intervention. Characteristic changes of DPP-4 level were observed in order to provide help for T1DM treatment.

Patients and methods

General data

The related content and methods of our study was approved by Ethics Department of People's Hospital of Rizhao. The family of patients in the two groups signed the informed consent after they were told intervention-related situation and state of the illness.

One hundred thirty-two children suffering T1DM (T1DM group) and 132 healthy children (NC group) admitted to our hospital from September 2014 to June 2015 were selected as research subjects. T1DM group contained 72 males and 60 females, with age of 1.5–10.0 years and an average age of 3.75±0.85 years, whose course of disease was 3 months to 9 years, with average course of disease of 1.24±0.31 years. The child patients in the group met the child T1DM-related diagnostic criteria, excluding the patients with complicated malignant tumors, various organic pathologic changes and previous hypoglycemia. The NC group contained 57 males and 75 females, with age of 0.5–14 years and average age of 4.65±1.75 years. The results of physical examination did not show fasting blood-glucose (FBG) increase and/or other organic or functional disease. This study was approved by the Ethics Committee of People's Hospital of Rizhao. Signed written informed consents were obtained from guardians of all participants before the study.

Methods

The general data of the children were collected, including gender, age, duration of diabetes, and blood pressure, height, weight and body mass index (BMI) were measured. Portable glucometer (Medtronic, Inc., Minneapolis, MN, USA) was used to detect FPG. Peripheral venous blood of 4 ml was extracted from the patients, then measured by DPP-4 detection kit, and the serum concentration of DPP-4 was recorded. The biochemical indexes such as blood fat and transaminase were tested by Roche Modular Fully Automatic Biochemical Analyzer (Roche Diagnostics, Indianapolis, IN, USA). Based on the insulin intervention treatment, 3 months of medical nutritional intervention strategy was carried out. Medical nutritional therapy and education group trained the parents (the daily caregiver of child patients), to teach them carbohydrate calculation method, food exchange portion and glucose resultant index, lasting for 3 days and 2 h per day. During everyday training, the nutritionist demonstrated the choice, collocation and cooking of meal on site. After all parents in research group finished the training, they provided meals for the children according to the requirement and measured blood glucose at least 7 times per day.

Statistical analysis

Software SPSS 20.0 (IBM SPSS, Armonk, NY, USA) was used to analyze data. P<0.05 was considered to indicate a statistically significant difference. Experiment data that conformed to normal distribution was presented by mean ± standard deviation (mean ± SD), which was tested by t-test or one-way analysis of variance. DPP-4 level and clinical characteristic data were processed by Pearson's correlation analysis and multiple linear regression analysis.

Results

Comparison of clinical characteristics between two groups

Compared with NC group, BMI, FPG and HbA1c from T1DM group were obviously higher than those of control group (P<0.01). Level of DPP-4 in T1DM serum was also significantly higher than in NC group (P<0.05) (Table I).

Table I.

Analysis of clinical features of patients in two groups (mean ± SD).

Groups	Cases (M/F)	Age (years)	Duration of diabetes (months)	SBP (mmHg)	DBP (mmHg)	BMI (kg/m2)	AST (U/1)	ALT (U/1)
NC	132 (57/75)	3.65±0.87	–	118.5±30.5	70.4±22.8	19.7±2.4	17.2±2.1	12.7±3.6
T1DM	132 (72/60)	3.27±1.24	10.78±6.51	102.4±23.7	67.4±34.7	23.6±1.8	16.5±2.4	3.2±4.9
t-test	–	0.68	–	0.17	0.45	1.32	0.78	0.44
P-value	–	>0.05	–	>0.05	>0.05	<0.05	>0.05	>0.05
Groups	GGT (U/1)	FPG (mmol/1)	HbA1C (%)	TC (mmol/l)	HDL-C (mmol/l)	LDL-C (mmol/l)	DPP-4 (mmol/l)
NC	18.6±2.2	4.37±0.85	4.70±0.43	185.4±20.6	67.5±13.5	98.5±10.2	2.63±0.38
T1DM	17.3±3.6	8.24±3.36	7.82±1.03	177.3±21.2	68.4±11.8	102.3±21.6	5.83±2.31
t-test	0.67	1.79	1.56	0.75	0.52	0.63	2.35
P-value	>0.05	<0.05	<0.05	>0.05	>0.05	>0.05	<0.05

NC, normal children group; T1DM, type 1 diabetes mellitus; M, male; F, female; BMI, body mass index; DDP-4, dipeptidyl peptidase-4.

Comparison of FPG and DPP-4 level of T1DM group before and after treatment

Insulin was applied in T1DM group and FPG was recorded during treatment every day. It was found that, compared with the state before the treatment, FPG level of T1DM group decreased after the treatment. concomitantly, the level of DPP-4 increased, but was still higher than that in NC group (P<0.05) (Table II).

Table II.

Comparison of FPG and DPP-4 level of T1DM group before and after insulin treatment (mean ± SD).

Groups	Cases (n)	FPG (mmol/l)	DPP-4 (mmol/l)
NC	132	4.28±0.49	2.72±0.58
T1DM
Before treatment	132	8.24±3.36	5.83±2.31
After treatment	132	5.37±0.76	4.24±1.28
F-value		1.20	2.73
P-value		<0.05	<0.05

DPP-4, dipeptidyl peptidase-4; T1DM, type 1 diabetes mellitus; NC, normal children group.

Influence of medical nutritional intervention on the level of DPP-4 in children suffering T1DM

After receiving medical nutritional intervention treatment, FPG, BMI, LDL-L and TG level in children suffering T1DM decreased (P<0.05), while the level of DPP-4 did not change obviously (P>0.05) (Table III).

Table III.

Influence of nutrition intervention on BMI and DPP-4 level of children with T1DM (mean ± SD).

Groups	Cases (n)	FPG (mmol/l)	BMI (kg/m2)	LDL-C (mmol/l)	TC (mmol/l)	DPP-4 (mmol/l)
Before	132	8.24±3.36	23.6±1.8	102.3±21.6	185.4±20.6	5.83±2.31
After	132	7.27±1.36	20.7±3.3	87.4±12.6	157.3±20.8	5.74±1.66
F-value	–	1.20	1.74	2.37	4.38	0.46
P-value	–	<0.05	<0.05	<0.05	<0.05	>0.05

BMI, body mass index; DPP-4, dipeptidyl peptidase-4; T1DM, type 1 diabetes mellitus.

Correlation analysis between DPP-4 level in serum and other factors of children patients with T1DM

Pearson's correlation analysis showed that DPP-4 level had a positive correlation with diabetic duration, BMI and gamma (γ)-glutamyl transpeptidase (GGT) for the children with TIDM (P<0.05) (Table IV). DPP-4 level was taken as a dependent variable, and gender, age, duration of diabetes, SBP, DBP and other indexes were taken as independent variable, to analyze by multiple linear regression analysis. Multiple linear regression analysis showed that BMI may be a factor influencing the level of DPP-4 in the serum of T1DM children (P<0.05) (Table V).

Table IV.

Correlation analysis between DPP-4 and clinical detection index (r).

Index	Gender	Age (years)	Duration of diabetes (months)	SBP (mmHg)	DBP (mmHg)	AST (U/l)	ALT (U/l)	logGGT (U/l)	FPG (mmol/l)	BMI (kg/m2)
DPP-4
r	0.02	0.35	0.17	0.16	0.28	0.24	0.15	0.06	0.38	0.14
P-value	>0.05	>0.05	<0.05	>0.05	>0.05	>0.05	>0.05	<0.05	>0.05	<0.05

DDP-4, dipeptidyl peptidase-4; BMI, body mass index.

Table V.

Multiple linear regression analysis of DPP-4 level of factors for child patients with T1DM.

						(95% CI)
Variables	β	SE	β′	t	P-value	Upper limit	Lower limit
Duration of diabetes	0.531	0.14	0.764	0.412	>0.05	0.26	0.81
logGGT	0.581	0.10	0.642	0.652	>0.05	0.39	0.78
BMI	0.768	0.08	0.871	0.981	<0.05	0.61	0.92

DDP-4, dipeptidyl peptidase-4; T1DM, type 1 diabetes mellitus; BMI, body mass index.

Discussion

From previous studies of T2DM, it was found that DPP-4 is an intestinal enzyme, also named as ferment, playing a role in the small intestine and that was involved in the decomposition of protein within human body (9–11). Among them, GLP-1, a protein that is decomposed by DPP-4, is also called insulinotropic harmonic polypeptide-1, which is a hormone material secreted by intestinal cells. The physiological function of GLP-1 is complicated. It is thought to reduce blood glucose by stimulating insulin, controlling glucagon, inhibiting gastric emptying and promoting islet cell regeneration (12–14). GLP-1 can also secrete glucagon and the decomposition of hepatic glycogen by reducing pancreas cell function to promote blood glucose into liver and skeletal muscle, thereby compounding glycogen that is reserved for blood glucose regulation (15,16). DPP-4 inhibitor has been applied to clinic for T2DM, but for the patients with T1DM, we have not found a favorable ancillary drug (17). From the comparison of DPP-4 level between child patients and normal children, it was found that DPP-4 level of child patients with T1DM significantly increased, according to the feature of insulin absolute shortage for T1DM. In addition, after the treatment with insulin, the DPP-4 level of children with T1DM decreased obviously, so we speculated that it may depend on the function characteristics of DPP-4, which mainly included (18–20): i) The function of regulating pancreas β cells and secrete insulin; ii) the unique insulin dependence feature of secreting and regulating blood glucose when glucose is increasing in human body. Therefore, it has a defensive function for pancreas β cells, which can significantly reduce the apoptosis of pancreas β cells and prolong the life span of islet cells (8). Due to the insulin dependence feature of GLP-1, insulin absolute shortage can lead to the increase of GLP-1 level for child patients with T1DM, then DPP-4 level will increase as well. In a previous study conducted by Lamers et al (9) reported that among the patients with T1DM in Japan, DPP-4 level in serum was higher than that of healthy people. So hoping to find a substitution or partial substitution of insulin to cure T1DM. Nevertheless, for the children with T1DM, the research of this kind still lack sufficient evidence.

Our study also found that DPP-4 level had a positive correlation with duration of diabetes, BMI and GGT among the child patients with diabetes; multiple linear regression analysis showed that DPP-4 was influenced by BMI mostly. By this token, for the child patients with T1DM, it is necessary to adopt targeted treatment strategy of nutrition intervention, so as to improve DPP-4 level by controlling BMI. The study of DPP-4 originated from 30- or 40-year age groups. The scientists discovered incretin in the first place, with a releasing feature of secreting by enteroendocrine cells in small intestine after eating. Moreover, one study (10) pointed out a case report of combination of insulin and DPP-4 inhibitor during the treatment of T1DM (10). This type of research is absent among Han ethnicity child patients with T1DM. From our results, in previous studies, DPP-4 level was influenced by the interactions of many factors so that the relation among these confounding factors was not explained clearly. The present study analyzed the relation between these confounding factors and DPP-4 by multiple linear regression analysis and found BMI as the breakthrough. Therefore, we hold that reasonable nutrition ingestion and control can improve the dietary nutrition of child patients, which is of great benefit for the control of T1DM and pancreas islet function.

Furthermore, we designed a clinical experiment of nutrition intervention, and it was found that after 3 months of clinical nutritional intervention, BMI of children with T1DM significantly improved (P<0.05); however, DPP-4 level did not appear obviously changed compared with that of prior treatment (P>0.05). Based on this result, we concluded that nutrition intervention could not improve insulin level in human body directly and could not directly improve DPP-4 level either. However, BMI may be one of the important factors influencing DPP-4 level, but the influence and time require further research.

In conclusion, DPP-4 level increased obviously among the child patients with T1DM. The aim of this study was to reach an accurate understanding of DPP-4 level in serum of Han ethnicity children with T1DM. Therefore, we can adopt nutritional intervention with pertinence to improve the condition of the child patients by controlling BMI.