The new drug for type 1 diabetes has been approved in the United States, but it has not yet been marketed in China, how to choose the insulin treatment regimen for children in China?

On November 17, 2022, the US FDA approved Tzield (teplizumab) injection for the delayed treatment
of type 1 diabetes mellitus (T1DM) in adults with stage 2 type 1 diabetes and children aged 8 years and older.
However, the drug has not yet been marketed in China, and children with T1DM in China are still
mainly treated with insulin.

Image from the official website of the US Food and Drug Administration

Type 1 diabetes mellitus (T1DM) is a pediatric endocrine disease that seriously endangers children's health, with an incidence of 2/100,000~5/100,000 in China in recent years, and the incidence shows a trend
of younger age.
The earlier the onset of childhood T1DM, the greater the risk of death from chronic complications, so clinicians need to identify, diagnose, and intervene early in childhood T1DM
.

Diagnostic criteria for diabetes mellitus in children

According to the diagnostic criteria for diabetes issued by the World Health Organization (WHO) in 2019, diabetes can be diagnosed if one of the following 4 conditions is met:

1.
Fasting blood glucose≥ 7.
0 mmol/L;

2.
Blood glucose ≥11.
1 mmol/L [glucose 1.
75 g/kg (body weight), maximum glucose 75 g] 2 h after oral glucose tolerance load;

3.
HbA1c≥6.
5%；

4.
Random blood glucose ≥ 11.
1 mmol/L with symptoms and signs
of diabetes.

For those who meet the above criteria but do not have signs or symptoms of diabetes, it is recommended to repeat the test on the following 1 day to confirm the diagnosis
.

Classification of diabetes mellitus in children

According to the new WHO consensus, diabetes can be divided into 6 subtypes, of which T1DM, T2DM, mixed diabetes and other special types of diabetes are mainly 4 subtypes
that are closely related to children.
The specific classification is detailed in the following table:

Insulin therapy for T1DM in children

Patients with T1DM require complete or partial exogenous insulin replacement to maintain the balance and survival
of glucose metabolism in the body due to absolute deficiency of their own insulin secretion.
Therefore, the treatment regimen for children with T1DM is mainly
insulin therapy.

Start time

Children with new-onset T1DM should start insulin therapy as soon as possible, and those with positive urine ketones should use insulin within 6 hours; Insulin
should also be used initially when diabetes is poorly classified, such as DKA, random blood glucose concentration ≥13.
9 mmol/L, and/or HbA1c>8.
5%.

Treatment

At present, the mainstream models are multiple daily injections (MDI) and continuous subcutaneous insulin injection (CSII).

1.
Dose setting: the total daily insulin of new T1DM is generally 0.
5~1.
0 U/(kg·d), but it is recommended to start with 0.
5 U/(kg·d) under 3 years old; The honeymoon phase is usually < 0.
5 U/(kg·d), and before puberty (outside the partial remission period) is 0.
7~1.
0 U/(kg·d); Puberty is 1.
0~1.
5 U/(kg·d), and some can reach 2 U/(kg·d).
<b10> It should be noted that insulin of animal origin and premixed insulin
are not recommended for children.

2.
Dose allocation: Based on the individualized needs of the child's condition, the doctor and parents communicate in detail to help the child choose an individualized treatment plan, from 2 times a day to MDI and CSII treatment
.

(1) 2 times a day program: that is, short-acting or fast-acting + intermediate-acting before breakfast, short-acting or fast-acting + intermediate-acting regimen before dinner, intermediate-acting insulin accounts for 40%~60% of the total amount of 1 day, and the ratio of short-acting or fast-acting to medium-acting for the first time is about 1:2
.
The starting dose is assigned to insulin about 2/3 of the total amount for 1 day before breakfast and about 1/3 before dinner, after which it is added or decreased
according to blood glucose.

(2) MDI program: mealtime + basic program, commonly used 3 meals before short-acting + bedtime short-acting insulin or 3 meals before fast-acting + bedtime long-acting insulin, intermediate-acting or long-acting insulin can be interchanged as appropriate, puberty may need to divide basal insulin into 2 doses before breakfast and
bedtime.

3.
Insulin injection equipment:

(1) Insulin injection needle and pen: commonly used is disposable sterile insulin syringe, injection pen is mainly graduated 1 U or 0.
5 U two
.

(2) Indications for CSII treatment: children with T1DM; Those who fluctuate greatly and use MDI regimens but still cannot be controlled steadily; Dawn phenomenon severely leads to poor overall blood sugar control; Frequent hypoglycemia, especially at night, unperceived hypoglycemia and severe hypoglycemia; Those who have irregular schedules and cannot eat on time; Reluctance to accept MDI options; Children
with gastroparesis or long eating times.

Monitoring of acute complications

hypoglycemia

The blood glucose < 3.
9 mmol/L in children with diabetes is the threshold for clinical intervention, and the blood glucose < 3.
0 mmol/L can cause central nervous system and cognitive dysfunction<b10>.

Treatment:

(1) Blood glucose < 3.
9 mmol/L and conscious mind, give glucose 10~15 g or other equivalent glucose carbohydrates, if it is still hypoglycemic after 15 minutes, the above dose needs to be repeated; Treatment with CSII, such as blood glucose < 2 mmol/L, requires suspension of the insulin pump<b10>.

(2) Severe hypoglycemia without coma, 10% glucose injection 2 ml/kg intravenous bolus, with convulsive coma given 10% glucose 4 ml/kg intravenous bolus; The dose of glucagon is intravenous, intramuscular, or subcutaneous depending on the child's weight, with body weight ≥ 1 mg for 25 kg and 0.
5 mg
for < 25 kg.

(3) Repeated hypoglycemia, 10% glucose 2~5 mg/(kg·min) maintenance, close monitoring of the child's blood glucose and other symptoms
during treatment.

DKA with ketone body monitoring

The incidence of DKA in children with T1DM is 15%~75%, and it is more likely to occur under 5 years old, and the cause of death is cerebral edema
of 60%~90%.
The main component of blood ketone body β-hydroxybutyric acid ≥ 0.
6 mmol/L indicates metabolic decompensation

Treatment:

(1) When blood ketones are 0~0.
6 mmol/L, blood glucose is routinely measured; If blood glucose > 15 mmol/L, add blood ketones
.

(2) When blood ketones are 0.
6~1.
5 mmol/L and blood sugar > 15 mmol/L, blood glucose and blood ketones are rechecked every 2 hours, and if blood ketones do not decrease, consider adjusting the insulin dose
.

(3) When blood ketones are 1.
6~3.
0 mmol/L and blood glucose > 15 mmol/L, it is necessary to evaluate whether DKA is made, and recheck blood glucose and blood ketones every 2 hours;

(4) When blood ketone ≥ 3 mmol/L and blood glucose > 15 mmol/L, it is necessary to evaluate whether DKA is made, and blood glucose and blood ketones
are checked every 1 hour.

brief summary

Children and adolescents with T1DM are different from adults, and their management is more challenging, such as large differences in body size and development, so primary doctors should consider the age and developmental maturity of children, individualized treatment plan, treatment compliance and other issues
when managing T1DM in children.

References:

[1] Endocrinology, Genetics and Metabolism Group, Pediatrics Branch of Chinese Medical Association, Editorial Board of Chinese Journal of Pediatrics.
Expert consensus on standardized diagnosis and treatment of type 1 diabetes mellitus in children in China (2020 edition)[J].
Chinese Journal of Pediatrics,2020,58(6):447-454.
DOI:10.
3760/cma.
j.
cn112140-20200221-00124.

[2] Diabetes Branch of Chinese Medical Association.
Guidelines for the treatment of insulin in type 1 diabetes mellitus in China[J].
Chinese Journal of Practical Rural Doctors,2017,24(8):40-44.
DOI:10.
3969/j.
issn.
1672-7185.
2017.
08.
025.

Choreography: Jiaojiao | Reviewer: Yin

： ，
。   ， ，