INTRODUCTION — Type 1 diabetes mellitus (T1DM), one of the most common chronic diseases in childhood, is caused by insulin deficiency following destruction of the insulin-producing pancreatic beta cells. It most commonly presents in childhood, but one-fourth of cases are diagnosed in adults. T1DM remains the most common form of diabetes in childhood, accounting for approximately 80 percent of new diagnoses of diabetes in patients ≤19 years of age in the United States, despite the increasing rate of type 2 diabetes mellitus (T2DM) [1,2].

The epidemiology, presentation, and diagnosis of T1DM in children and adolescents are presented here. The pathogenesis of T1DM and the management and complications of childhood T1DM are discussed separately:

●(See "Pathogenesis of type 1 diabetes mellitus".)

●(See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)

●(See "Diabetic ketoacidosis in children: Clinical features and diagnosis".)

●(See "Diabetic ketoacidosis in children: Treatment and complications".)

●(See "Complications and screening in children and adolescents with type 1 diabetes mellitus".)

The assessment and management of individuals presenting during infancy with hyperglycemia also are discussed separately. (See "Neonatal hyperglycemia".)

EPIDEMIOLOGY — The incidence of childhood T1DM varies based upon geography, age, gender, family history, and ethnicity.

Geographical variation — The incidence of childhood T1DM varies worldwide [3].

The highest reported incidences of T1DM occur in Finland and Sardinia (37 to 65 per 100,000 children younger than the age of 15 years) [3,4]. In the United States, the annual incidence of T1DM in children and adolescents is 22.3 per 100,000 overall, with substantial differences between race/ethnic groups (27.3 per 100,000 in non-Hispanic White youth, 20.8 per 100,000 in Black youth, and 16.3 per 1000,000 in Hispanic youth) [5].

Age and gender — The age of presentation of childhood-onset T1DM has a bimodal distribution, with one peak at four to six years of age and a second in early puberty (10 to 14 years of age) (figure 1) [6-8]. Overall, approximately 45 percent of children present before 10 years of age [9].

Although most autoimmune diseases are more common in females, there appears to be no gender difference in the overall incidence of childhood T1DM [1,2]. However, in some studies, T1DM occurs more frequently in males. Globally, the ratio of males to females diagnosed with T1DM in young adulthood is approximately 1.5:1 [10]. The same male to female ratio also was reported in children younger than six years of age in an observational study from Massachusetts [11].

Time trends — Until the early 2000s, the incidence of childhood T1DM was reported to be rising worldwide, with reported increases of 2 to 5 percent per year in Europe, the Middle East, and Australia [4,12-15]. In the United States, the overall incidence of T1DM rose from 1.48 per 1000 in 2001 to 2.15 per 1000 in 2017 (a 45 percent relative increase over 16 years) [2]. Meanwhile, the incidence rose from 19.5 per 100,000 in 2002-2003 to 22.3 in 2014-2015 (annual percent change 1.9 percent) (figure 2) [5]. The reasons for this trend remain unknown.

The time trends within age groups vary among populations. A report using data from 17 European countries between 1989 and 2003 revealed a greater annual increase among younger children (5.4 percent among 0- to 4-year-olds and 4.3 percent among 5- to 9-year-olds) compared with adolescents (2.9 percent among 10- to 14-year-olds) [14]. By contrast, in the United States between 2001 and 2017, the annual change in prevalence slightly decreased for young children (-0.5 percent for 0- to 4-year-olds and -0.2 percent for 5- to 9-year-olds), while increasing for older children (1 percent for 10- to 14-year-olds and 2.5 percent for 15- to 19-year-olds) [2]. Similar decreases in trends among younger children born after 2000 were seen in studies from Sweden [16] and New Zealand [17].

RISK FACTORS — Both genetic and environmental factors contribute to the risk of developing T1DM. (See "Pathogenesis of type 1 diabetes mellitus".)

Genetic susceptibility — The lifetime risk of developing T1DM is significantly increased in close relatives of a patient with T1DM [3,18-20]:

●No family history – 0.4 percent

●Offspring of an affected mother – 1 to 4 percent

●Offspring of an affected father – 3 to 8 percent

●Offspring with both parents affected – Reported as high as 30 percent [21,22]

●Non-twin sibling of affected patient – 3 to 6 percent by age 20 years [19] and 10 percent by 60 years [23]

●Dizygotic twin – 8 percent

●Monozygotic twin – 30 percent within 10 years of diagnosis of the first twin [24] and 65 percent concordance by age 60 years [25]

In the United States, there also are ethnic differences in incidence of T1DM [2]. In a study that sampled several large multiethnic populations in 2017, the highest prevalence was seen in non-Hispanic White youth, followed by Black, Hispanic, Asian or Pacific Islander, and American Indian youth (2.79, 2.18, 1.56, 0.76, and 0.56 cases per 1000 children 0 to 19 years old, respectively) (figure 3) [2].

These observations of familial and ethnic risk factors are most likely the consequences of gene polymorphisms in the major histocompatibility complex or other genetic susceptibility regions [3]. Details regarding genetic susceptibility and the genes that increase the risk of T1DM are presented elsewhere. (See "Pathogenesis of type 1 diabetes mellitus", section on 'Genetic susceptibility'.)

Other risk factors — In genetically susceptible individuals, exposure to one or more environmental agents appears to trigger an immune response that ultimately causes destruction of the insulin-producing pancreatic beta cells. Identification of these factors should lead to a better understanding of the pathogenesis of the disease and aid in developing strategies to prevent T1DM [3]. (See "Pathogenesis of type 1 diabetes mellitus", section on 'Environmental factors' and "Prevention of type 1 diabetes mellitus".)

Reports have linked each of the following factors to an increased risk of T1DM; however, none of these associations have been verified and many have been contradicted by other studies. They include:

●Viral infections, particularly respiratory or enterovirus infections [26,27]

●Immunizations

●Diet

●Higher socioeconomic status

●Obesity [28-31]

●Vitamin D deficiency

●Perinatal factors such as maternal age, history of preeclampsia, and neonatal jaundice

●Low birth weight decreases the risk of developing T1DM, while high birth weight for gestational age and lower gestational age at birth may increase the risk for T1DM [32]

Seasonal variation has been suggested in some studies, with a higher reported incidence of T1DM in colder as compared with warmer months, particularly in children [33-35]. However, another study did not find a seasonal variation in girls and reported a higher incidence in the summer months for boys [36].

A more complete description of environmental factors and their potential link to T1DM is discussed separately. (See "Pathogenesis of type 1 diabetes mellitus", section on 'Environmental factors'.)

CLINICAL PRESENTATION — The stages of T1DM have been redefined as [37,38]:

●Stage 1 – Multiple islet autoantibodies, normal blood glucose, and presymptomatic

●Stage 2 – Multiple islet autoantibodies, raised blood glucose, and presymptomatic

●Stage 3 – Islet autoimmunity, raised blood glucose, and symptomatic

●Stage 4 – Longstanding T1DM

However, for clinical purposes, the usual initial presentations remain [39]:

●Classic new onset of chronic polydipsia, polyuria, and weight loss with hyperglycemia and ketonemia (or ketonuria)

●Diabetic ketoacidosis (DKA)

●Silent (asymptomatic) incidental discovery

Classic new onset — Hyperglycemia without acidosis is the most common presentation of childhood T1DM in most populations. Patients typically present with the following symptoms:

●Polyuria – Polyuria occurs when the serum glucose concentration rises significantly above 180 mg/dL (10 mmol/L), exceeding the renal threshold for glucose, which leads to increased urinary glucose excretion. Glycosuria causes osmotic diuresis (ie, polyuria) and hypovolemia. Polyuria may present as nocturia, bedwetting, or daytime incontinence in a previously continent child. In children who are not toilet trained, parents may note an increased frequency of wet diapers and/or diapers that are unusually heavy (wet).

●Polydipsia – Polydipsia is due to enhanced thirst because of increased serum osmolality from hyperglycemia and hypovolemia. Despite the hypovolemia, patients may not have the classic signs of dry mucus membranes or decreased skin turgor.

●Weight loss – Weight loss is a result of hypovolemia and increased catabolism. Insulin deficiency in diabetic children impairs glucose utilization in skeletal muscle and increases fat and muscle breakdown. Initially, appetite is increased, but over time, children are more thirsty than hungry and ketosis leads to nausea and anorexia, contributing to weight loss.

Patients with these symptoms usually present in the ambulatory setting appearing slightly ill, with vague complaints such as weight loss and lethargy [11]. In a study from Ireland, the mean duration of symptoms before presentation was 10 days [40]. The classic symptoms of polyuria and polydipsia are present in more than 90 percent of patients, but these are not always the initial complaints and may become apparent only after obtaining a careful history (eg, nocturia and bedwetting, increased frequency and/or unusually wet diapers, and persistent thirst). Weight loss is a presenting symptom in approximately one-half of children.

Other presentations include perineal candidiasis, which is a relatively common presenting symptom in young children and in girls [11]. Visual disturbances are common because of alterations in the osmotic milieu of the lens and, to a lesser extent, the aqueous and vitreous humors, leading to changes in refractive index [41]. Children with longstanding hyperglycemia may present with cataracts [42,43]. (See "Cataract in children".)

Diabetic ketoacidosis — DKA (hyperglycemia and ketoacidosis) is the second most common form of presentation for T1DM in most populations. Symptoms are similar but usually more severe than those of patients without acidosis. In addition to polyuria, polydipsia, and weight loss, patients with ketoacidosis may present with a fruity-smelling breath and neurologic findings, including drowsiness and lethargy. DKA can be misinterpreted as an acute vomiting illness because classic pediatric symptoms of dehydration (decreased urination) are masked by the polyuria that is associated with glycosuria. (See "Diabetic ketoacidosis in children: Clinical features and diagnosis", section on 'Signs and symptoms'.)

The reported frequency of DKA as the initial presentation for childhood T1DM is approximately 30 percent but varies from 15 to 67 percent [44-46]. Young children (<6 years of age) or those from an adverse socioeconomic background are more likely to have DKA as their initial presentation of T1DM. Among children younger than age three years, more than one-half had DKA as their initial presentation of T1DM [44]. (See "Diabetic ketoacidosis in children: Clinical features and diagnosis", section on 'Epidemiology'.)

Children with DKA require hospitalization, rehydration, and insulin replacement therapy. (See "Diabetic ketoacidosis in children: Treatment and complications".)

Silent presentation — Some children will be diagnosed with T1DM before the onset of clinical symptoms. This presentation is least common and typically occurs in children who have another close family member with T1DM and are being closely monitored. The diagnosis often is made by either a family member or clinician with a high index of suspicion. Children with an affected close family member also may undergo pancreatic autoantibody screening to assess risk for the disease [47], although this is not a clinical care recommendation (see "Prediction of type 1 diabetes mellitus"). These children may be classified as having stage 1 or stage 2 diabetes, using International Society for Pediatric and Adolescent Diabetes guidelines [37]. The diagnosis of stage 2 diabetes is made based upon an elevated blood glucose concentration using the criteria outlined below. (See 'Diagnosis' below.)

Special populations

Infants — A variety of disorders can cause hyperglycemia during infancy. Although autoimmune classic T1DM can occur in the first year of life, neonatal diabetes is uncommonly, if ever, autoimmune in nature. Neonatal diabetes is a rare disorder caused by one of several genetic defects in pancreatic development or beta cell function. (See 'Differential diagnosis' below and "Neonatal hyperglycemia", section on 'Neonatal diabetes mellitus'.)

Young children — Young children (eg, <5 years of age) are more vulnerable to dehydration compared with older children because they are less able to compensate for pathologic processes by seeking fluids and increasing fluid intake (to replace ongoing urinary losses) [11]. In addition, children younger than six years of age are more likely to present with DKA because health care personnel and families less often suspect diabetes in this age group. This leads to a prolonged duration of illness and more severe metabolic decompensation before diagnosis [11,40,44,48,49].

Children in this age group also have polydipsia and polyuria, but these symptoms are difficult to detect if the child is still in diapers or is nonverbal and unable to communicate thirst. Therefore, it is often difficult to recognize these symptoms of hyperglycemia in young children, especially those younger than two years of age [11]. The history or presence of prolonged or recurrent candidal infection (usually in the diaper area) is an important clue that should raise suspicion about the possibility of diabetes mellitus in young children. Candidal infection was present at diagnosis in a significant proportion of children younger than six years with T1DM and especially in those younger than two years of age [11].

These patients often have been seen by a clinician for nonspecific complaints before the diagnosis [11]. In this vulnerable age group, a high index of suspicion is required for early diagnosis. When a young child presents for evaluation of dehydration, abdominal pain, or fatigue, the clinician should include diabetes in the differential diagnosis and consider measuring serum glucose and testing for glucosuria.

DIAGNOSIS — T1DM is one of several different types of diabetes mellitus. The initial step is to diagnose diabetes. The second step is to differentiate T1DM from other causes of diabetes, based upon the clinical presentation of the patient and laboratory studies. (See 'Type 1 versus type 2 diabetes' below and 'Other causes of diabetes' below.)

Diagnostic criteria for diabetes — Diabetes mellitus is diagnosed based upon one of the following four signs of abnormal glucose metabolism (table 1) [3,50,51]:

●Fasting plasma glucose ≥126 mg/dL (7 mmol/L) on more than one occasion. Fasting is defined as no caloric intake for at least eight hours.

●Random venous plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia.

●Plasma glucose ≥200 mg/dL (11.1 mmol/L) measured two hours after a glucose load of 1.75 g/kg (maximum dose of 75 g) in an oral glucose tolerance test. Most children and adolescents are symptomatic and have plasma glucose concentrations well above ≥200 mg/dL (11.1 mmol/L); thus, an oral glucose tolerance test is seldom necessary to diagnose T1DM.

●Glycated hemoglobin (A1C) ≥6.5 percent (using an assay that is certified by the National Glycohemoglobin Standardization Program). This criterion is more useful to diagnosis of type 2 diabetes mellitus (T2DM) in adults and should be confirmed by hyperglycemia.

Based upon the guidelines of the American Diabetes Association, these diagnostic criteria resemble those used in adults with diabetes. Unless unequivocal symptomatic hyperglycemia is present, the diagnosis should be confirmed by repeat testing. (See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults".)

A1C measures the percent of hemoglobin A bound to glucose via non-enzymatic glycation and indicates the average blood sugar levels for 10 to 12 weeks before the time of measurement. A1C ≥6.5 percent is now an accepted criterion for diagnosis of diabetes in adults [51]. However, the diagnostic utility of A1C for children is less well established than for adults. A1C values ≥6.5 percent are diagnostic of diabetes in adults, but levels <6.5 percent do not exclude diabetes. Of note, in one study from Germany, all children with symptomatic new-onset T1DM had an A1C ≥6.35 percent, whereas those with transient hyperglycemia had A1C values ranging from 4.5 to 6.1 percent [52].

Individuals with abnormal hemoglobins or rapid destruction of red blood cells may have a measured A1C value that does not accurately reflect their average blood sugar values. The accuracy of measurements in individuals with abnormal hemoglobins will improve with the use of improved techniques for assessing A1C and with standardization of A1C measurements. For example, hemoglobin variants and derivatives interfere very minimally with the commercially available boronate affinity chromatography technique [53]. However, rapid turnover of hemoglobin will still affect the reported A1C level. (See "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults", section on 'A1C'.)

Glycosuria is suggestive of diabetes but not diagnostic. For example, patients with renal glucosuria or Fanconi syndrome will present with glycosuria but have normal plasma glucose concentrations. Similarly, the presence of islet-specific autoantibodies supports the diagnosis of T1DM (as discussed in the next section) but is not sufficient to start treatment with insulin in the absence of hyperglycemia.

Type 1 versus type 2 diabetes — T1DM is characterized primarily by insulin deficiency, whereas T2DM is characterized primarily by insulin resistance with relative insulin deficiency. As the incidence of T2DM increases in children and adolescents, it becomes increasingly important to distinguish type 1 from type 2 disease because long-term management differs. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)

No set of criteria or diagnostic test can consistently distinguish between T1DM and T2DM. Therefore, differentiating between the two types is based upon a combination of the clinical presentation and history, often supported by laboratory studies (table 2).

Clinical characteristics:

●Body habitus – Patients with T2DM are usually obese (body mass index ≥95^th percentile for age and gender). In contrast, children with T1DM are usually not obese and often have a recent history of weight loss, although up to 25 percent are overweight (body mass index ≥85^th to 95^th percentile) [54].

●Age – Patients with T2DM generally present after the onset of puberty, whereas those with T1DM often present at an earlier age. Approximately 45 percent of children with T1DM present before 10 years of age [9]. By contrast, almost all cases of T2DM present after 10 years of age (figure 1). (See 'Age and gender' above.)

●Insulin resistance – Patients with T2DM frequently have acanthosis nigricans (a sign of insulin resistance), hypertension, dyslipidemia, and polycystic ovary syndrome (in girls). These findings are less likely in children with T1DM. As an example, in studies in the United States, 50 to 90 percent of youth diagnosed with T2DM have acanthosis nigricans [55,56]. Among those clinically diagnosed with T1DM, up to 25 percent have biochemical evidence of insulin resistance and approximately 12 percent have acanthosis nigricans [56].

●Family history – Up to 10 percent of patients with T1DM have an affected close relative, whereas 75 to 90 percent of those with T2DM have an affected close relative [55,57].

Laboratory testing – The following laboratory tests are often helpful in differentiating between T1DM and T2DM. We suggest including them in the evaluation:

●Antibodies – Although there is no specific test to distinguish between the two types of diabetes, T1DM is suggested by the presence of circulating, islet-specific pancreatic autoantibodies against glutamic acid decarboxylase 65 (GAD65), the 40K fragment of tyrosine phosphatase (IA2), insulin, and/or zinc transporter 8 (ZnT8) [3]. However, the absence of pancreatic autoantibodies does not rule out the possibility of T1DM. Up to 30 percent of individuals with the classical appearance and presentation of T2DM have positive autoantibodies and may have a slowly progressive type of autoimmune diabetes [58]. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)

●Insulin and C-peptide levels – High fasting insulin and C-peptide levels suggest T2DM. Levels are inappropriately low or in the normal range relative to the concomitant plasma glucose concentration in T1DM. At presentation, insulin and C-peptide levels may be suppressed by severe hyperglycemia and illness. It is usually best to assess these levels after the newly diagnosed patient has recovered from acute illness. Ethnicity may modify C-peptide levels in children with new-onset T1DM, with Hispanic (but not African American children) demonstrating higher C-peptide levels than non-Hispanic White children, after controlling for confounders [59].

Insulin deficiency in T1DM most commonly results from autoimmune destruction of pancreatic beta cells and is referred to as type 1A diabetes(figure 4) [56]. A minority of patients with clinical features of T1DM have no detectable autoantibodies and are categorized as having type 1B diabetes. In these patients, there is no evidence of autoimmune beta cell destruction and no other cause has been identified. (See "Classification of diabetes mellitus and genetic diabetic syndromes" and "Pathogenesis of type 1 diabetes mellitus".)

Some patients may have mixed features and are difficult to classify. As an example, in a registry study in the United States, pediatric diabetes was classified based upon the presence or absence of beta cell autoimmunity and the presence or absence of insulin sensitivity [56]. More than 70 percent of patients fell into traditional categories of autoimmune and insulin-sensitive T1DM (55 percent) or nonautoimmune and insulin-resistant T2DM (16 percent). An additional 20 percent had both autoimmunity and insulin resistance, a pattern typical for obese patients with T1DM. The remaining 10 percent of patients were insulin sensitive in the absence of islet cell autoimmunity, most of whom were clinically categorized as T1DM (ie, type 1B diabetes) and the remainder as T2DM (suggesting that these patients need additional evaluation for the possibility of monogenic diabetes, formerly referred to as maturity-onset diabetes of the young [MODY]). (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Distinguishing type 1 from type 2 diabetes' and 'Other causes of diabetes' below.)

DIFFERENTIAL DIAGNOSIS

Other causes of hyperglycemia — In the previously healthy child, diabetes mellitus is by far the most common cause of clinically significant hyperglycemia. Other considerations include:

●Critically ill patients – Patients with septic shock or other critical illnesses often have abnormalities in glycemic control, leading to either hypoglycemia or hyperglycemia. (See "Septic shock in children: Ongoing management after resuscitation", section on 'Manage glucose abnormalities'.)

●Medication – Children receiving intravenous infusions containing glucose, or those who receive acute sympathomimetic agents or high-dose glucocorticoids, may display elevations in blood glucose that revert to normal after treatment is complete.

●Neonatal hyperglycemia – Causes of hyperglycemia in a neonate include excessive glucose infusion, prematurity, stress, sepsis, drugs, and transient or permanent neonatal diabetes mellitus. (See "Neonatal hyperglycemia".)

Other causes of diabetes — T1DM is distinguished from other diseases that cause diabetes by patient characteristics, history, and laboratory studies. This approach is similar to that used to differentiate type 1 from type 2 diabetes, as discussed above. (See 'Type 1 versus type 2 diabetes' above.)

The following diseases that cause diabetes are discussed in greater detail separately. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)

●Diseases of the exocrine system – Cystic fibrosis, hereditary hemochromatosis, and chronic pancreatitis. (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Diseases of the exocrine pancreas'.)

●Endocrine abnormalities in glucose regulation – Cushing syndrome, growth-hormone excess, glucagon-secreting tumors, catecholamine excess in pheochromocytoma. With the exception of Cushing syndrome, these are all extremely rare. This possibility should be evaluated in patients presenting with Cushingoid features (such as central obesity, facial plethora, dorsocervical fat pad, and delayed linear growth). This is usually best accomplished by measuring 24-hour urinary cortisol excretion or salivary cortisol at 11:00 PM or midnight two or more times; additional testing may be required. It is important to recognize that children with Cushing syndrome may not manifest the classic features seen in adults. However, a deceleration of growth velocity despite increasing weight should raise concern for Cushing syndrome in a growing child. It is very rare for a child with Cushing syndrome to present with hyperglycemia, although it is relatively common in adults. (See "Epidemiology and clinical manifestations of Cushing's syndrome", section on 'Glucose intolerance'.)

●Drug-induced diabetes – A number of drugs (eg, glucocorticoids, HIV protease inhibitors, cyclosporine, L-asparaginase, and tacrolimus) and atypical antipsychotic agents can impair glucose tolerance by inhibiting insulin secretion, increasing hepatic glucose production, or causing insulin resistance (table 3). In addition, newer immune checkpoint inhibitors used in the treatment of melanoma and other malignancies have been associated with the development of insulin-deficient diabetes [60]. (See "Pathogenesis of type 2 diabetes mellitus", section on 'Drug-induced hyperglycemia' and "Pathogenesis of type 1 diabetes mellitus", section on 'Treatment with checkpoint inhibitor immunotherapy'.)

●Monogenic diabetes (formerly referred to as maturity-onset diabetes of the young [MODY]) – Monogenic diabetes is a clinically heterogeneous disorder characterized by noninsulin-dependent diabetes presenting at a young age, with autosomal dominant transmission and lack of autoantibodies. Many different genetic abnormalities have been identified, each leading to a different type of disease. Monogenic diabetes should be suspected in a patient presenting with noninsulin-dependent diabetes at a young age (<25 years), with autosomal dominant transmission across three generations, lack of islet autoantibodies, and lack of acanthosis nigricans. The diagnosis of monogenic diabetes is made by performing diagnostic genetic testing through direct sequencing of the gene. (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Monogenic diabetes (formerly called maturity onset diabetes of the young)'.)

●Neonatal diabetes mellitus – Neonatal diabetes is a rare cause of hyperglycemia in infants. It can be transient or permanent and usually is caused by mutations in one of several genes that encode proteins that affect the function of the pancreatic beta cell (eg, proteins that are subunits of the ATP-sensitive potassium channel). Most of the infants are small for gestational age, and they present with weight loss, volume depletion, hyperglycemia, and glucosuria with or without ketonuria and ketoacidosis. The natural history and management of diabetes in these infants depends on the genetic defect, as discussed in a separate topic review. (See "Neonatal hyperglycemia", section on 'Neonatal diabetes mellitus'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Type 1 diabetes (The Basics)" and "Patient education: My child has diabetes: How will we manage? (The Basics)" and "Patient education: Giving your child insulin (The Basics)")

●Beyond the Basics topics (see "Patient education: Type 1 diabetes: Overview (Beyond the Basics)")

SUMMARY — Type 1 diabetes mellitus (T1DM) is the result of insulin deficiency caused by destruction of the pancreatic beta cells. T1DM is one of the most common chronic diseases of childhood. It accounts for approximately two-thirds of all cases of diabetes in patients younger than 19 years of age.

●Epidemiology

•The incidence of childhood T1DM varies worldwide, ranging from 0.1 to 65 per 100,000 children younger than the age of 15 years. The age of presentation has a bimodal distribution, with peaks at four to six years of age and between 10 and 14 years of age (figure 1). In the United States, the incidence of T1DM is 22.3 per 100,000 annually, with the highest rates in non-Hispanic White children and adolescents (figure 3). (See 'Epidemiology' above.)

•Although there appears to be no overall gender difference in the incidence of childhood T1DM, in select populations (eg, European adolescents), there seems to be an increased risk for males (3:2 male to female ratio). (See 'Age and gender' above.)

●Risk factors

•The risk of T1DM is moderately increased in children with an affected close relative, which is most likely due to gene polymorphisms in the major histocompatibility complex and other susceptibility areas. (See 'Genetic susceptibility' above.)

•Although exposure to an environmental agent(s) in genetically susceptible individuals appears to trigger the destruction of the insulin-producing pancreatic beta cell, no factor(s) has been definitively identified. (See 'Risk factors' above and "Pathogenesis of type 1 diabetes mellitus".)

●Clinical presentation – Childhood T1DM usually presents with the classic signs and symptoms resulting from hyperglycemia, including polyuria, polydipsia, weight loss, and lethargy. Diabetic ketoacidosis (DKA) is often the initial presentation for T1DM, especially in children younger than six years of age and in children of all ages with poor access to health care. Children also may be identified by screening for the disease before the onset of symptoms. (See 'Clinical presentation' above and "Prediction of type 1 diabetes mellitus".)

In young children, the diagnosis of T1DM is often missed because it may be difficult to recognize the symptoms of hyperglycemia in this age group. Children younger than two years of age are particularly likely to have a delay in diagnosis. In these patients, a history or presence of prolonged candidal infection should prompt consideration of diabetes mellitus and measurement of blood and urine glucose concentrations. (See 'Young children' above.)

●Diagnosis – The diagnosis of diabetes is based upon any one of four detected abnormalities of glucose metabolism (table 1) (see 'Diagnostic criteria for diabetes' above and "Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults"):

•Fasting plasma glucose ≥126 mg/dL (7 mmol/L) on at least two occasions

•Symptoms of hyperglycemia and a plasma glucose ≥200 mg/dL (11.1 mmol/L)

•Plasma glucose ≥200 mg/dL (11.1 mmol/L) measured two hours after a standard glucose load in an oral glucose tolerance test

•Glycated hemoglobin (A1C) ≥6.5 percent – This criterion is more useful in the diagnosis of type 2 diabetes mellitus (T2DM) in adults and should be confirmed by hyperglycemia

●Differential diagnosis – T1DM often can be distinguished from other causes of diabetes (such as T2DM) by clinical presentation and laboratory studies. Although no one diagnostic test can distinguish between the two types of diabetes, T1DM is suggested by the presence of serum autoantibodies against islet cells, glutamic acid decarboxylase 65 (GAD65), the 40K fragment of tyrosine phosphatase (IA2), insulin, or zinc transporter 8 (ZnT8) and by low or inappropriately normal fasting C-peptide and insulin levels with concomitant hyperglycemia. C-peptide and insulin levels are generally not required to make the diagnosis. (See 'Type 1 versus type 2 diabetes' above and 'Other causes of diabetes' above.)