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