bubble_chart Overview

Diabetes in childhood refers to diabetes that occurs before the age of 15 or 20, previously collectively referred to as juvenile diabetes. Since the causes of diabetes in childhood vary, leading to differences in clinical presentation, treatment, and prognosis, the term "childhood diabetes" has been abandoned due to its unclear definition. This article focuses on type 1 diabetes, which is more prevalent among children and adolescents.

bubble_chart Epidemiology

The incidence of IDDM varies significantly depending on factors such as region and ethnicity. In European and American countries with the highest prevalence rates, it can reach 100–200 per 100,000 population. A 1980 survey of 140,000 children under the age of 14 across 14 provinces and cities in China found a diabetes prevalence rate of 5 per 100,000. IDDM can occur at any age before 30, with the youngest confirmed case we observed being a 10-month-old infant. There is no gender difference. In recent years, occasional cases of children diagnosed with NIDDM have been reported. Moreover, with the increasing number of obese children in China, those with impaired glucose tolerance should be monitored for early diagnosis of NIDDM.

bubble_chart Etiology

The widely accepted view is that IDDM occurs on the basis of genetic susceptibility genes, leading to injury and destruction of B cells, ultimately resulting in the failure of pancreatic islet B-cell function. However, there are still many unresolved issues among the aforementioned factors. Based on current research findings, the following is an overview:

1. Genetic Factors The heritability of IDDM and NIDDM differs. Studies on monozygotic twins have shown that the concordance rate for NIDDM is 100%, while for IDDM it is only 50%, indicating that IDDM is a polygenic genetic disorder influenced by environmental factors in addition to genetic predisposition.

2. Environmental Factors Over the years, numerous reports have linked the onset of IDDM to infections by various viruses, such as rubella virus, mumps virus, coxsackievirus, and encephalomyocarditis virus. Animal experiments also provide insufficient evidence that viral infections or chemical toxins like streptozotocin and alloxan can directly damage pancreatic islet B cells and cause diabetes. Genetically susceptible animals can develop diabetes simply through dietary methods. In summary, environmental factors may include viral infections, chemical toxins in the environment, and certain nutritional components, all of which may exert cytotoxic effects on B cells in individuals with susceptibility genes, triggering changes in immune function and ultimately leading to IDDM. Environmental factors are highly complex and likely play a significant role in the varying incidence rates of IDDM across different regions and ethnic groups. Additionally, severe mental and physical stress, infections, and stress can significantly worsen the metabolic state in IDDM, leading to insulin resistance and elevated blood sugar levels, which may cause ketoacidosis in susceptible individuals.

3. Immunological Factors Early postmortem examinations of newly diagnosed IDDM patients revealed acute and chronic lymphocytic infiltration in the pancreatic islets, a condition known as insulitis. Subsequent studies found various autoantibodies in the blood of IDDM patients, such as islet cell antibodies (ICA), islet cell surface antibodies (ICSA), and anti-insulin antibodies. It is now believed that ICA and similar antibodies are the result of islet cell destruction. Additionally, it was discovered that lymphocytes from patients can inhibit insulin release from B cells. There is an increased ratio of helper T cells to suppressor T cells, as well as an increase in killer (K) cells. Furthermore, it has been demonstrated that T lymphocytes in patients exhibit a series of functional receptors on their surfaces, along with an increase in Ia antigen-bearing T cells and other immune function alterations. Various theories have been proposed to explain the mechanisms behind these immune changes. In summary, alterations in immune function are a critical component in the pathogenesis of IDDM.

Based on different disease causes, diabetes in childhood can be classified as follows:

1. Insulin-Dependent Diabetes Mellitus (IDDM), also known as Type 1 diabetes. It is further divided into two subtypes: Type 1A and Type 1B. Type 1A refers to IDDM caused by the combined involvement of genetic, immune, and environmental factors and is representative of IDDM. Type 1B refers to IDDM occurring within familial autoimmune diseases, representing a component of autoimmune disorders. This article focuses primarily on Type 1A IDDM (hereinafter referred to as IDDM).

2. Non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes, is further divided into obesity type and severe obesity type. In the past, when NIDDM occurred in childhood, it was referred to as maturity-onset diabetes mellitus of the young (MODY). The term MODY has not been entirely abandoned. This condition is inherited in an autosomal dominant manner. However, there are also sporadic cases of type II diabetes in childhood.

3. Malnutrition-related diabetes mellitus (MRDM) can present with pancreatic fibrosis and calcification or islet calcification, along with a history of protein deficiency.

4. Other types include diabetes caused by pancreatic diseases, endocrine disorders, drugs or chemicals, as well as diabetes resulting from certain genetic syndromes or insulin receptor abnormalities.

5. Impaired glucose tolerance (IGT) The vast majority (over 90%) of diabetes cases in childhood are insulin-dependent diabetes mellitus type IA (IDDM, type IA). Type IA dependence means that patients must receive insulin injections to prevent diabetic ketoacidosis, unconsciousness, and death.

bubble_chart Pathogenesis

In IDDM, the destruction of pancreatic beta cells leads to reduced insulin secretion, causing metabolic disturbances. Insulin has extensive effects on energy metabolism, activating target cell surface receptors, promoting intracellular glucose transport, directly supplying energy or converting glucose into glycogen, enhancing fat synthesis, and inhibiting fat breakdown. Insulin also strengthens protein synthesis, promoting cell growth and differentiation, and stimulates glycolysis while inhibiting gluconeogenesis. In IDDM patients, insulin deficiency results in the absence of postprandial insulin secretion increase, leading to persistently elevated blood glucose levels after meals. When hyperglycemia exceeds the renal threshold, glycosuria occurs, causing energy loss in the body and increased mobilization of fat breakdown metabolism, leading to elevated ketone body production. Due to insulin deficiency, growth may be impaired, and weight loss can occur before symptoms like polyuria and polydipsia appear.

Additionally, in diabetes, counter-regulatory hormones such as glucagon, adrenaline, cortisol, and growth hormone increase, exacerbating metabolic disturbances and pushing diabetes into a decompensated state. These counter-regulatory hormones promote glycogenolysis, increase gluconeogenesis, and enhance fat breakdown, producing various intermediate fat metabolites and ketone bodies. Hyperglycemia, hyperlipidemia, and hyperketonemia cause osmotic diuresis, leading to polyuria, dehydration, and acidosis. Increased plasma osmolality results in thirst (polydipsia) and significant weight loss.

During ketoacidosis, brain function is injured, oxygen utilization decreases, and symptoms such as drowsiness, impaired consciousness, and eventual unconsciousness gradually appear. In severe acidosis, CO₂

retention occurs, and to expel excess CO₂, the respiratory center is stimulated, causing irregular deep and rapid breathing (Kussmaul respiration). The acetone in the breath produces a distinctive odor (rotten fruit smell).

bubble_chart Clinical Manifestations

IDDM often has a relatively acute onset, with most patients developing symptoms due to triggers such as infection, emotional agitation, or improper diet. The symptoms include polydipsia, polyuria, polyphagia, and weight loss, collectively referred to as the "three excesses and one deficiency" symptoms of IDDM. However, in infants, polyuria and polydipsia are not easily noticeable, and dehydration and ketoacidosis can occur rapidly. Young children may experience enuresis due to increased nocturia. Polyphagia is not necessarily present in all patients, as some children may have normal or reduced appetite. Rapid weight loss or emaciation, fatigue, and lethargy are also common. If polydipsia and polyuria are accompanied by symptoms such as vomiting, nausea, anorexia, abdominal pain, diarrhea, or leg pain, diabetic ketoacidosis should be considered. Respiratory infections like fever and cough, skin infections, vaginal itching, and subcutaneous nodules may coexist with diabetes.

During physical examination, aside from weight loss and emaciation, there are generally no positive signs. In ketoacidosis, deep breathing with a ketotic odor, signs of dehydration, and altered consciousness may appear. Prolonged poor diabetes control can lead to growth retardation, short stature, delayed intellectual development, and hepatomegaly, known as diabetic dwarfism (Mauhiac syndrome). In advanced stages, internal visual obstruction, visual impairment, retinal lesions, or even blindness may occur. Other complications include proteinuria, hypertension (diabetic nephropathy), and eventually renal failure.

Natural course: The progression of IDDM follows a certain pattern. The time from symptom onset to clinical diagnosis is usually within three months. This period, marked by various symptoms, is called the acute metabolic disturbance phase. About 20% of cases present with diabetic ketoacidosis, 20–40% with diabetic ketosis without acidosis, and the remainder with only hyperglycemia and glycosuria. All patients require insulin therapy. After treatment, symptoms disappear, blood glucose levels drop, and glycosuria decreases (from "+" to "-"), marking the onset of the remission stage, during which insulin requirements decrease. This stage lasts from several weeks to over a year, though it may be less noticeable in some patients. After the remission stage, patients gradually enter the intensification phase, where insulin dosage becomes relatively stable, marking the permanent diabetes phase. During adolescence, due to increased sex hormones and insulin resistance, insulin requirements rise again, and the condition becomes less stable. After adolescence, insulin needs decrease, and the condition stabilizes once more. Infections or stress can rapidly worsen the condition.

bubble_chart Auxiliary Examination

1. Glycosuria Qualitative glycosuria is usually frequently positive. In recent years, urine glucose test strips have been used to measure glycosuria by comparing it with standard colors. When test strips are unavailable, the Benedict's test is still employed: 9 drops of copper sulfate reducing reagent (Benedict's solution) are added to 1 drop of fresh urine and boiled. The results are interpreted as follows: blue indicates (-), green (+), yellow (++), orange-red (+++), and brick-red (++++). At the start of treatment, urine glucose should be measured four times daily—before breakfast, lunch, dinner, and bedtime. Each time, the bladder should be emptied 30 minutes before collecting urine for testing. Urine glucose reflects blood glucose levels during the interval between collections. During acute metabolic disturbances, four timed urine collections are also required: post-breakfast to pre-lunch, post-lunch to pre-dinner, post-dinner to bedtime, and overnight to pre-breakfast the next day. Each collection should record urine volume and test for glycosuria and ketonuria. Combining the results of these four collections provides a 24-hour urine volume and glycosuria measurement, offering a detailed basis for insulin adjustment. Additionally, 24-hour quantitative glycosuria should be measured periodically (every 2–4 weeks).

In diabetic ketoacidosis or ketosis, urine ketones are positive, and sometimes urine protein may also be positive.

2. Blood Routine blood tests are normal, but total white blood cell count increases during ketoacidosis. In untreated IDDM, random blood glucose levels are often >11 mmol/L (>200 mg/dL), while mild cases may show fasting blood glucose >6.7 mmol/L (120 mg/dL). Various blood lipid components are elevated when blood glucose is uncontrolled.

3. Glucose Tolerance Test If glycosuria is positive and fasting blood glucose is elevated, diabetes can be diagnosed without a glucose tolerance test. This test is used for patients with normal or borderline fasting blood glucose, elevated postprandial blood glucose, or occasional glycosuria who cannot be definitively diagnosed. The method involves fasting for 8–16 hours, followed by a fasting blood glucose measurement. The patient then orally ingests glucose (1.75 g/kg, up to a maximum of 75 g), dissolved in 2.5 mL of water per gram, consumed within 3 minutes (may be mixed with sugar-free juice for tolerance). Blood glucose is measured at ½, 1, 2, and 3 hours post-ingestion, with urine collected for glycosuria testing before each blood draw. Results: Normal fasting blood glucose is 4.4–6.7 mmol/L (80–120 mg/dL). At ½–1 hour post-glucose, levels are 8.4–10.08 mmol/L (150–180 mg/dL), returning to fasting levels by 2 hours, and potentially dropping below fasting levels by 3 hours while remaining within the normal range. All urine glucose tests should be negative. Impaired glucose tolerance (IGT) (previously called a diabetic curve) is defined as fasting blood glucose >6.7 mmol/L (120 mg/dL), 1-hour ≥10.08 mmol/L (180 mg/dL), 2-hour ≥7.8 mmol/L (140 mg/dL), or any single value above normal. For three days prior to the test, carbohydrate intake should not be less than 150 g/day. Avoid strenuous exercise, stress, and discontinue medications like hydrochlorothiazide and salicylates that affect glucose metabolism.

4. Glycosylated Hemoglobin Hemoglobin in red blood cells non-enzymatically binds with blood glucose or phosphorylated glucose to form glycosylated hemoglobin (HbA₁), with HbA_1c as its main component, primarily bound to glucose. Normal HbA_1c levels are 4–6%. In untreated diabetics, levels are often doubled, exceeding 12%. For treated IDDM patients, levels should ideally be <9% and no higher than 10%.

bubble_chart Diagnosis

1. Clinical Manifestations

(1) The onset is relatively acute. About one-third of children have a history of fever and infections of the upper respiratory tract, digestive tract, urinary tract, or skin before the onset.

(2) Polydipsia, polyuria, polyphagia with easy hunger, but weight loss, obvious emaciation, fatigue, and listlessness. Enuresis in young children after they have gained control of urination is often an early symptom of diabetes.

(3) Susceptibility to various infections, especially respiratory and skin infections. Female infants may also develop fungal vulvitis, with perineal irritation as a prominent symptom.

(4) Children with long-term unsatisfactory blood sugar control may develop internal visual obstruction within 1 to 2 years. In advanced stages, microvascular lesions can lead to retinal membrane damage and renal impairment.

2. Laboratory Tests

(1) Blood sugar: Fasting blood sugar >6.6mmol/L, 2-hour postprandial blood sugar >11.1mmol/L.

(2) Urine sugar: Pre-meal and bedtime urine samples are collected as "spot urine" (4 spot urines per day), while urine collected between two spot urines is termed "timed urine" (4 timed urines per day). Untreated individuals often test positive for urine sugar, with 24-hour urine sugar >5g.

(3) Glycated hemoglobin: Reflects the comprehensive average blood sugar level over the past two months and is a reliable indicator of long-term blood sugar control in children. >8.5–10% indicates grade I elevation. Untreated individuals or those with unsatisfactory control often exceed 14%.

(4) β-cell function test: During a glucose tolerance test, insulin and C-peptide levels are measured at various time points. Children show a significantly elevated blood sugar peak under glucose load, with no return to baseline levels after 2 hours, while insulin and C-peptide responses are low.

(5) Blood lipids: Untreated individuals exhibit significantly elevated blood lipids.

3. Ketoacidosis: Children may develop ketoacidosis due to acute infections, overeating, delayed diagnosis, or interrupted insulin therapy. The onset is acute, presenting with polydipsia and polyuria, along with anorexia, nausea, vomiting, abdominal pain, and generalized pain. Severe dehydration and metabolic acidosis symptoms include poor skin elasticity, sunken eyes, cherry-red lips, deep breathing, and a vinegar-like ketone odor in exhaled breath. In severe cases, unconsciousness or death may occur. Blood sugar >16.7mmol/L, urine sugar +++ to ++++, blood ketones >1:2 positive, urine ketones positive, blood pH <7.3, HCO₃- significantly reduced.

4. Hyperosmolar nonketotic unconsciousness: Severe hyperglycemia (blood sugar often 41.6–83.3mmol/L), blood sodium >145mmol/L, plasma osmolality >300mosm/kg, dehydration, and unconsciousness. However, blood ketones are not elevated, and urine ketones are negative or weakly positive. Sometimes, diabetic ketoacidosis patients may develop iatrogenic hyperosmolar nonketotic unconsciousness due to excessive glucose-saline infusion during treatment, which should be noted.

5. Hypoglycemic reaction: Children are highly sensitive to insulin and prone to hypoglycemic reactions during treatment, often occurring when insulin is most potent—3–4 hours after regular insulin injection or during the night or early morning before breakfast for intermediate or long-acting insulin. Symptoms include pallor, weakness, fatigue, dizziness, hunger, sweating, palpitations, and even spasms, unconsciousness, or death.

bubble_chart Treatment Measures

IDDM is a lifelong endocrine and metabolic disorder. The treatment of IDDM is comprehensive, including insulin, dietary management, physical adaptability, and should also emphasize psychological and mental therapy.

The goal of IDDM treatment is to help patients achieve the best possible "health" state, bringing their metabolic control close to the upper limit of normal, maintaining fasting blood glucose at 6.7–7.8 mmol/L (120–140 mg/dl), and postprandial 2-hour blood glucose close to ascites levels. Clinically, the following needs must be met: ① Complete elimination of symptoms such as polydipsia and polyuria. ② Prevention of recurrent diabetic ketoacidosis. ③ Avoidance of hypoglycemia. ④ Maintenance of normal growth and pubertal development. ⑤ Prevention of obesity. ⑥ Early diagnosis and timely treatment of concurrent infections and autoimmune sexually transmitted diseases. ⑦ Timely identification of patients' psychological barriers and emotional changes, providing mental support and assistance to resolve these issues. ⑧ Persistent encouragement for patients to maintain good metabolic control, strict adherence to prescribed insulin dosages and dietary arrangements, and a regular lifestyle to prevent or delay the onset of chronic complications. Since IDDM patients have prolonged lifespans after treatment and require lifelong efforts to manage their condition, this effort may cause frustration and resistance in children. Doctors should patiently assist patients and avoid reprimanding them.

During IDDM treatment, regular follow-ups (once every 1–2 weeks after discharge, then once every 2–3 months after stabilization) are necessary. Before follow-ups, patients should test their 2-hour postprandial blood glucose on the day of the visit and collect 24-hour urine for glucose quantification the day before. If possible, glycated hemoglobin (HbA1c or HbA1) should be measured each time, aiming for HbA1 < 10.5% and average blood glucose < 11.2 mmol/L (200 mg/dl). Patients with automatic glucose meters should test their blood glucose four times daily, or at least twice. Those without glucose meters should test urine glucose before each meal and at bedtime, totaling four times daily. Ideal 24-hour urine glucose should be < 5 g/24h, with a maximum of no more than 20 g/24h. Annual lipid profile tests, including cholesterol, triglycerides, HDL, and LDL, should be conducted, with treatment adjustments if lipid levels are elevated. Blood pressure should be measured at each follow-up, and an annual fundus examination is recommended.

Treatment methods for IDDM:

1. Insulin Therapy Insulin is the key to successful IDDM treatment. The type, dose, and injection method of insulin all affect efficacy. In recent years, many new insulin products and injection methods have been developed.

(1) Insulin Preparations and Effects There are dozens of insulin products worldwide, categorized by duration of action into rapid-acting, intermediate-acting, and long-acting types. Based on composition, they include insulin extracted from porcine or bovine pancreas, pure human insulin synthesized via recombinant DNA genetic engineering, semi-synthetic insulin, and modified porcine insulin (by replacing one amino acid in the insulin structure). Currently, China only has short-acting regular insulin (RI) and long-acting protamine zinc insulin (PZI). In recent years, imported intermediate-acting NPH (neutral protamine Hagedorn) and other pure human insulin products have become available. The onset and peak action times of various insulin preparations are shown in Table 31-18.

Insulin preparations also come in different specifications, such as 1ml containing 40u, 80u, and 100u, so attention must be paid to identification during use. When RI is mixed with intermediate-acting insulin (NPH), the solubility of RI decreases, and it should be injected immediately after mixing before administration. The general mixing ratio for the two is approximately RI:NPI at 4:6. When RI is mixed with PZI, the ratio must not be less than 3:1.

(2) Initial dosage and adjustment of insulin therapy. The daily insulin requirement for children with IDDM is generally 0.4u～1.0u/kg/d. On the first day of treatment, a dosage of 0.5u～0.6u/kg is considered safer. The total daily dose is divided equally into 3～4 injections, administered 20～30 minutes before each meal and before the bedtime snack. Using 60% NPH and 40% RI, the dose is divided into two injections: two-thirds of the total daily dose before breakfast and one-third before dinner. The insulin injected before breakfast covers post-breakfast and post-lunch insulin needs, while the insulin injected before dinner covers post-dinner and bedtime snack insulin needs until the next morning. Adjust the next day's insulin based on the blood glucose or urine glucose results from the treatment day. When RI is administered in 3～4 injections, the adjustment of insulin dosage should be based on the first morning urine glucose and pre-lunch urine glucose or blood glucose from the previous day to adjust the next morning's RI dose or breakfast. Adjust the pre-dinner RI dose or dinner based on the post-dinner urine glucose and bedtime urine glucose or blood glucose from the previous day. If fluctuations occur after the condition stabilizes, first investigate potential causes such as diet, infection, climate, and emotional changes before adjusting insulin and treating the underlying disease cause.

When mixing RI with PZI for injection, the maximum PZI dose should not exceed 0.3u/kg, with the remainder given as RI. For three daily injections, a small amount of PZI (2～4u) or one-third of the RI dose can be added before dinner. Be cautious to prevent nocturnal hypoglycemia. When mixing insulin, always draw RI first, followed by NPH or PZI.

Intensive insulin therapy with insulin injection pens or infusion pumps. The insulin injection pen is an improvement over conventional syringes, using nozzle pressure and ultra-fine needles to deliver insulin subcutaneously, reducing skin injury and the psychological stress of injections. This method is convenient and painless, using regular insulin (RI) and long-acting insulin (ultralente) (packaged compatibly with the pen). When switching from a conventional syringe to an insulin pen, the original insulin dosage should be reduced by 15-20%, with careful monitoring of blood and urine glucose for adjustments. Continuous subcutaneous insulin infusion (CSII) involves the continuous delivery of a basal insulin dose via an insulin pump, using RI and NPH for stability, with additional RI administered before each meal. CSII may help maintain blood glucose at normal levels. Initially, hospitalization is required for observation and dose adjustment, with the total dosage generally set at 80% of the usual amount. The basal infusion accounts for 40% of the total, with 20% added before breakfast, 15% each before lunch and dinner, and 10% before bedtime snacks. Pre-meal boluses should be administered 20-30 minutes before eating. Special attention should be paid to monitoring blood glucose at 3 AM and 7 AM to promptly detect the Somogyi phenomenon or dawn phenomenon.

(3) Complications during insulin therapy

① Hypoglycemia Severe hypoglycemia in diabetic patients is very dangerous. The brain primarily relies on glucose oxidation for energy. In diabetes, brain tissue does not utilize ketones for oxidation, so hypoglycemia can lead to permanent brain injury. In mild cases, normal counterregulatory hormones may allow blood sugar to recover naturally. However, in long-term patients, the glucagon response to hypoglycemia is impaired, and the adrenaline response is also reduced, making spontaneous recovery slower and increasing the risk of hypoglycemic seizures. Diabetic patients experiencing hypoglycemia should promptly consume a snack or a sugar-containing beverage.

② Chronic insulin overdose (Somogyi phenomenon) Chronic insulin overdose often causes blood sugar to drop in the early hours of sleep without obvious symptoms. The resulting hypoglycemia triggers increased secretion of counterregulatory hormones, leading to elevated blood sugar by morning. This is known as the "low-high blood sugar reaction" or Somogyi phenomenon. If daytime blood sugar and urine sugar fluctuations are significant, and insulin dosage exceeds 1.5 U/kg/day without adequate control, blood sugar or urine sugar should be measured at 2–3 AM. If hypoglycemia or negative urine sugar is detected, insulin dosage should be reduced.

③ Chronic insulin insufficiency Patients persistently experience high blood sugar, incomplete resolution of diabetic symptoms, 24-hour urine sugar >25 g, slowed growth in children, hepatomegaly, hyperlipidemia, and hyperglycemia, increasing the risk of ketoacidosis. Dietary adjustments and increased insulin dosage should be implemented to control blood sugar within the upper normal range, allowing growth to return to normal.

④ Local or systemic allergic reactions Due to the purification of insulin products, allergic reactions are rare. Local redness, swelling, or urticaria may occur at the injection site. Allergic reactions may resolve with continued use. If persistent, switching to purified human insulin is recommended.

⑤ Insulin resistance When a patient requires >2 U/kg/day of insulin without ketoacidosis and still fails to control hyperglycemia (after excluding the Somogyi phenomenon), it is termed insulin resistance. If possible, measuring blood insulin and insulin antibodies may reveal elevated levels. Adding a small dose of corticosteroids for a few days may improve resistance, or switching to purified human insulin may reduce the required dosage.

⑥ Subcutaneous fat atrophy or hypertrophy at insulin injection sites Rotating injection sites can prevent this issue. Switching to purified human insulin may also reduce subcutaneous fat atrophy.

2. Dietary therapy The goal of dietary therapy for IDDM is to stabilize blood sugar levels close to normal, reducing complications. Diabetic children should follow a structured meal plan.

Total daily calories should consist of 50–55% carbohydrates, 15–20% protein, and 30% fat (calculated in grams). Fats should be vegetable oils (unsaturated fats), avoiding fatty meats and animal fats. Daily calories are divided into three meals and three snacks: breakfast (25% of total calories), lunch (25%), dinner (30%), two snacks between meals (5% each), and a bedtime snack (10%). Carbohydrates in each meal are key in determining blood sugar and insulin requirements. The glycemic index of foods is categorized as low, medium, or high (see table).

Table: Glycemic index of carbohydrate foods

3. Exercise Therapy Exercise is an essential part of normal growth and development for children and holds even greater significance for children with diabetes. Exercise helps maintain caloric balance and control weight, promotes cardiovascular function, improves lipoprotein composition in the blood, and aids in preventing coronary heart disease. During exercise, muscle energy consumption increases 7 to 40 times compared to rest. The energy primarily comes from fat metabolism and the breakdown of muscle glycogen. Exercise enhances muscle sensitivity to insulin, thereby improving glucose utilization and aiding in blood sugar control. The type and intensity of exercise should be tailored to the child's age and physical ability. Some experts recommend that school-aged children with IDDM engage in at least one hour of appropriate exercise daily. Adjustments to insulin dosage and diet must be carefully managed during exercise, such as reducing insulin or adding snacks before physical activity. Diabetic patients should exercise at fixed times daily and understand the relationship between calorie intake, insulin dosage, and exercise intensity.

4. Treatment of Diabetic Ketoacidosis Diabetic ketoacidosis (DKA) is one of the critical emergencies in pediatric clinical practice. Every pediatrician should be familiar with the characteristics of DKA to ensure timely diagnosis and proper treatment.

In IDDM ketoacidosis, clinical symptoms may initially resemble infections such as upper respiratory or urinary tract infections, followed by vomiting, nausea, dehydration, and acidosis. Alternatively, symptoms may begin with excessive thirst and urination, later progressing to reduced urine output or going unnoticed. Other symptoms may include abdominal pain, diarrhea, or joint and muscle pain, followed by lethargy, drowsiness, irregular deep breathing, or even unconsciousness. Blood test changes may reveal hyperglycemia, hyperketonemia, hyperlipidemia, electrolyte imbalances, and potassium deficiency, though serum potassium may appear normal before treatment. Blood pH <7.35, HCO₃- reduction, and other signs of acidosis may also be present.

Physicians should promptly and accurately diagnose DKA. Assessing cardiac and renal function, as well as any history of diabetes or prior episodes of ketoacidosis, is crucial for planning fluid therapy. After obtaining the patient's medical history, blood and urine samples should be collected for necessary tests, and treatment should begin immediately.

Laboratory tests include: blood glucose, blood ketones, blood gas analysis, and electrolytes such as K⁺, Na⁺, Cl^-, CO₂CP, BUN, and a complete blood count. Urine tests for ketones and glucose should also be performed. An ECG may be necessary in some cases.

Management of Ketoacidosis:

(1) Fluid Therapy Fluid therapy aims to correct dehydration, acidosis, and electrolyte imbalances. Intravenous fluids should be administered immediately after initial diagnosis and blood sample collection for lab tests. Until lab results are available to estimate plasma osmolality, fluid administration should be cautious. Typically, start with 20 ml/kg of normal saline infused within one hour. Further fluid composition should be determined after lab results are obtained. If severe dehydration leads to oliguria or anuria, and no urine output is observed after administering 20–40 mg/kg of saline, extreme caution is required. The patient may be in renal anuria or even hyperosmolar unconsciousness, and excessive fluid administration or organ edema should be prevented.

During ketoacidosis, the body excretes excessive glucose and ketones from the blood, along with Na⁺ and K⁺. Osmotic diuresis also leads to the loss of mineral salts such as phosphorus and magnesium.

The total input fluid volume and electrolytes are determined based on the degree of dehydration. In diabetic ketoacidosis, fluid requirements are generally estimated as grade II dehydration, with the total infusion volume calculated at 80–120 ml/(kg·d), plus ongoing fluid losses (urine output) or alternatively calculated as 1500 ml/m² of body surface area. In the first 8 hours after treatment initiation, half of the required fluid volume is administered, with the remaining volume infused over the subsequent 16 hours.

After the initial infusion of normal saline, the next step involves continuing normal saline or switching to half-strength saline based on serum sodium levels. The latter is prepared by adding an equal volume of sterile distilled water to normal saline. Subsequently, the solution can be changed to one-third strength or a maintenance fluid without glucose. Potassium salts (3–6 mmol/kg) can be added once urine output begins during fluid therapy.

Following fluid infusion and insulin administration, ketone metabolism generates HCO₃^-. When blood pH > 7.2, NaHCO₃ is generally unnecessary to correct acidosis, and lactate should not be used. If blood pH < 7.2, isotonic (1.4%) NaHCO₃ must be administered to correct acidosis. The required NaHCO₃ dose is calculated using the following formula:

HCO₃ deficit = (15 - measured HCO₃^-) × body weight (kg) × 0.6.

Initially, half of the calculated dose is administered over 1–2 hours, with slower infusion rates for more severe acidosis. The remaining dose is given only if blood pH remains < 7.2. Generally, NaHCO₃ should not exceed 2–3 mmol/kg every 2 hours. Rapid or excessive NaHCO₃ infusion may cause hypernatremia and alkalosis. Since NaHCO₃ crosses the blood-brain barrier slowly while CO₂ diffuses rapidly, overly rapid correction of acidosis can lead to alkalosis, hypokalemia, and worsened central nervous system acidosis, potentially resulting in death.

(2) Application of Insulin For diabetic ketoacidosis, it is best to use a small dose of insulin administered via continuous intravenous drip. Calculate the insulin dosage for 3-4 hours at 0.1 U/kg/hour, add it to 180–240 mL of normal saline, and administer it through another infusion bottle at a constant rate. An infusion pump can be used to control the infusion speed, maintaining it at 1 mL per minute or ensuring the hourly insulin dosage is delivered. Infants under 4 years old are more sensitive to insulin, so the dosage can be reduced to 0.05 U/kg/hour. If blood glucose exceeds 28 mmol/L (>500 mg/dL), the dosage can be increased to 0.15 U/kg/hour. Alternatively, if blood glucose fails to decrease by more than 20% of the pretreatment level after 2 hours of insulin infusion, the dosage may also be increased to 0.15 U/kg/hour, with blood glucose rechecked after 1 hour. Generally, blood glucose declines at a steady slope after intravenous insulin administration, but the rate of decline varies among individuals. Blood glucose should be monitored every 1–2 hours during insulin infusion. When blood glucose is >14 mmol/L (250 mg/dL), glucose-containing fluids should not be administered. Once blood glucose ≤14 mmol/L (250 mg/dL), glucose solution should be added, with a fixed ratio of 2 U insulin per 5 g glucose, administered separately through two infusion bottles while continuing the insulin drip to maintain blood glucose at 8.4–11.2 mmol/L (150–200 mg/dL). Use 2.5–5% glucose solution, administering 1.5–2.5 U insulin per 5 g glucose to maintain blood glucose at least above 5.6–8.4 mmol/L (100–150 mg/dL). As blood glucose decreases, the insulin infusion rate should be slowed to 0.02–0.06 U/kg/hour, while continuing glucose-containing fluids until ketoacidosis is fully corrected. Before discontinuing the infusion, check blood glucose and administer 0.25 U insulin subcutaneously. After 30 minutes, stop all infusions and provide a meal or beverage.

After the acute phase of ketoacidosis, the patient begins to eat. On the first day, the subcutaneous insulin dose is calculated at 1u/(kg·d), divided into 4 injections administered before breakfast, lunch, dinner, and bedtime snacks. The insulin dose can also be determined based on the blood glucose level after stopping intravenous insulin, with the calculation shown in Table 31-20. The initial subcutaneous insulin dose can also be calculated based on clinical experience and body weight: 20–30 kg: 4u, ~40 kg: 6u, ~50 kg: 8u, and ~60 kg: 10u. The next day's dosage is adjusted based on blood or urine glucose levels. Regular insulin can be administered 3–4 times daily or switched to RI + NPH ₂ injections.

Table 31-20 Calculation of Required Single Insulin Dose Based on Blood Glucose Level

When ketoacidosis is complicated by infection, appropriate antibiotic treatment should be administered based on the infection site and estimated pathogen.

5. Morbid Hyperosmolarity (MH) The definition of increased osmolarity is a serum osmolarity >310 mmol/L. Many children with IDDM experiencing ketoacidosis may have blood glucose levels as high as ≥33.6 mmol/L (600 mg/dl), which may indicate hyperosmolarity, mostly grade I.

Morbid hyperosmolarity (MH) refers to a plasma osmolarity >375 mmol/L and blood glucose >78.4 mmol/L (1400 mg/dl), which is life-threatening with a high mortality rate. In children, MH often occurs after central nervous system injury, leading to irritability and thirst, prompting excessive intake of juice or soda. For such patients suspected of having diabetes, delayed necessary treatment can be fatal.

When a patient only has grade I plasma hyperosmolarity, cerebral hyponatremia may be present. Although blood glucose is not very high, cerebral edema may exist, and such patients should also be managed as morbid hyperosmolarity. For those with cerebral edema but no plasma hyperosmolarity or hyperglycemia, but with a history of excessive water or hypotonic fluid intake, they should also be treated as morbid hyperosmolarity as early as possible. IDDM patients with MH may present with or without ketosis, but the importance of measuring plasma osmolarity should not be overlooked in either case.

The mortality rate of pathological hyperosmolar state is very high, and disseminated intravascular coagulation may occur, making treatment extremely difficult. Due to severe dehydration, acute renal failure may develop, requiring peritoneal dialysis. The mortality rate of hyperosmolar patients with ketoacidosis is lower than that of non-ketotic hyperosmolar patients.

Monitoring of Pathological Hyperosmolar Patients Pathological hyperosmolar patients are often in an unconscious state, indicating central nervous system injury. When serum osmolarity increases, brain cells dehydrate, which can lead to rupture of brain membrane blood vessels, causing subdural hemorrhage, increased blood viscosity, and shock. Additionally, it may result in a stirred pulse and venous thrombosis, with disseminated intravascular coagulation leading to bleeding. Finally, excessive administration of hypotonic fluids and insulin may cause blood glucose and plasma osmolarity to drop too rapidly, leading to brain edema and increased intracranial pressure. Due to the complex and critical nature of pathological hyperosmolar states, intracranial pressure should be clinically monitored. Relying solely on clinical neurological examinations to diagnose brain edema often means the condition is already in an advanced stage. If computer monitoring of extramembrane pressure is used during treatment, although invasive and risky, careful operation minimizes the risk and proves extremely useful for MH.

Assessment of Blood Volume: In the treatment of MH patients, overly rapid volume expansion can cause brain edema, while too slow expansion prolongs the anuric phase in the kidneys and worsens acidosis. Monitoring central venous pressure during volume expansion to reduce shock provides information on fluid status and cardiac function tension, indirectly preventing excessive or insufficient renal fluid administration and guiding appropriate fluid infusion. Central venous pressure measurement is also useful for monitoring blood pressure, both of which are crucial in treating MH patients.

Treatment of Pathological Hyperosmolarity:

(1) The purpose of administering electrolytes and fluids is to revive the patient from shock and ensure adequate perfusion of internal organs.

(2) Gradually restore plasma osmolarity to normal while preventing the onset or worsening of brain edema.

To achieve these goals, careful monitoring of stirred pulse, blood pressure, extradural pressure, and urine output, along with analyzing their interactions, is necessary. Appropriate fluid replacement maintains central venous pressure within the normal range. If treatment causes increased intracranial pressure, measures such as hyperventilation, barbiturate coma, and head elevation should be taken to reduce it.

In treating pathological hyperosmolarity, it is widely agreed that isotonic or hypertonic solutions should be used to dilute blood glucose concentration, avoiding hypotonic solutions, as they can cause severe brain edema when plasma osmolarity becomes hypotonic. The osmolarity of the infused fluid should be no more than 40 mmol/L lower than the patient's plasma osmolarity. For example, if the patient's plasma osmolarity is 370 mmol/L, the infused fluid should be 330 mmol/L. This fluid can be prepared with normal saline plus 20–40 mmol/L KCl and a small amount of 5% NaHCO₄, but alkalosis should be prevented. NaHCO₃ should not be used if there is no acidosis. The infusion volume should meet the needs of adequate perfusion to prevent adverse effects from hypoperfusion, but excessive fluid administration should also be avoided to prevent irreversible brain edema. Recent studies suggest that replenishing losses and maintaining fluids at a total volume of <4 L/m² body surface area over 24 hours, with a 48–72-hour replenishment period, yields better outcomes than completing it within 24 hours.

Application of Insulin in MH During MH, it is necessary to lower blood sugar, but the rate should not be too rapid. If glucose in the blood enters muscle and adipose tissues too quickly due to insulin infusion, it will alter the oncotic pressure gradients. The effect of osmotic pressure reduction mainly occurs in the extracellular fluid space. Under hypotonic conditions, cells will absorb water, leading to central nervous system edema. Since children with MH are often insulin-dependent, insulin must be administered, but the dosage must be minimal. A dose of 0.05 U/kg per hour can be given, while children under 4 years old should receive 0.02 U/kg per hour. If blood sugar drops too rapidly even with this dose, the insulin amount can be further reduced. Some even advocate delaying insulin administration to reduce the risk of cerebral edema. If blood sugar drops sharply below 250 mg/dL due to insulin use, cerebral edema may occur. However, if blood sugar declines gradually and insulin is used appropriately to maintain this level, the likelihood of cerebral edema is lower. There is debate over whether insulin should be used in non-ketotic hyperosmolar states, whereas its use in ketotic hyperosmolar states is universally agreed upon for dose insulin therapy.

bubble_chart Prevention

Due to the immunological characteristics of IDDM, such as its association with HLA susceptibility, the infiltration of insulin-producing cells and the presence of anti-islet cell antibodies at the onset of the disease, as well as abnormalities in T-cell subset ratios, IDDM is considered an autoimmune disorder. For these reasons, immunotherapy is being considered for newly diagnosed patients, especially those who have just begun to experience elevated blood sugar levels. Studies in mice have shown that viral infections can trigger an immune process similar to human IDDM, leading to insulitis. If protection against these viral infections can be provided, animals may avoid developing chronic infections, offering hope for future applications in humans.

bubble_chart Complications

Acute Complications The most common acute complications of IDDM are diabetic ketoacidosis (DKA) and hypoglycemia, the former due to insulin deficiency and the latter to insulin excess. Additionally, various infections can occur at any time.

1. Ketoacidosis IDDM patients may develop ketoacidosis during acute infections, delayed diagnosis, overeating, or interruption of insulin therapy. Clinical manifestations are as described earlier. The incidence of ketoacidosis is higher in younger children. New IDDM patients presenting with ketoacidosis may be misdiagnosed with pneumonia, asthma, sepsis, acute abdomen, or meningitis, and differential diagnosis is necessary. In ketoacidosis, blood glucose may exceed 28.0 mmol/L (500 mg/dl), and blood ketones may exceed 10 mmol/L (200 mg/dl). Blood ketones include not only acetoacetate, β-hydroxybutyrate, and acetone but also various intermediate metabolites of fatty acid metabolism, such as α-valerone, 3-penten-2-one, and larger ketones, as well as fatty acids like adipic acid and sebacic acid, all of which are significantly elevated. The metabolic disturbances of fats in diabetic ketoacidosis are complex. During ketoacidosis, blood pH decreases, HCO₃^- is reduced, and blood sodium, potassium, and chloride levels are also below normal. Some patients may not exhibit low blood potassium before treatment, but potassium levels drop rapidly after insulin therapy. The qualitative test for urinary ketones uses nitroprusside, which reacts with acetoacetate but not with β-hydroxybutyrate or other ketones and fatty acids. Thus, the urinary ketone test may show a weak positive or even negative result. After initial treatment, acetoacetate production increases, and the urinary ketone reaction may strengthen.

2. Hypoglycemia Hypoglycemia in diabetic patients treated with insulin occurs due to excessive insulin dosage or failure to eat on time after insulin injection. Symptoms include palpitation, sweating, hunger, dizziness, and tremor. Severe cases may lead to hypoglycemic unconsciousness or even convulsions; delayed treatment can be fatal. Repeated hypoglycemic episodes may cause brain dysfunction or epilepsy.

3. Infections IDDM is a lifelong disease, and patients are susceptible to various infections at any time, including acute or chronic infections of the respiratory tract, urinary system, and skin. Even a grade I common cold can worsen the condition. Severe infections may lead to toxic shock. If treatment focuses solely on the infection while neglecting diabetes diagnosis and management, serious consequences may ensue, necessitating vigilance.

4. Diabetic Hyperosmolar Nonketotic Unconsciousness This condition is rare in children with IDDM and often occurs in patients with pre-existing neurological disorders. Diagnosis of hyperglycemic nonketotic unconsciousness as diabetic hyperosmolar nonketotic unconsciousness must occur in patients with pre-existing diabetes and should be distinguished from iatrogenic hyperglycemic unconsciousness caused by injections of hypertonic glucose saline. In diabetic hyperosmolar unconsciousness, blood glucose often exceeds 28–54 mmol/L (500–1000 mg/dl), blood sodium >145 mmol/L, and plasma osmolality >310 mmol/L, sometimes exceeding 370 mmol/L. Dehydration and unconsciousness are present, but blood and urinary ketones are not significantly elevated, and there is no acidosis. Treatment requires isotonic or hypotonic fluids (40 mmol/L or 20 mOsm/L below plasma osmolality). If plasma osmolality exceeds 370 mmol/L (370 mOsm/kg), hypertonic fluids >330 mmol/L are used. Insulin dosage should be small, and blood glucose reduction should be gradual to prevent rapid decreases in plasma osmolality, which may cause cerebral edema. This condition has a high mortality rate.