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Table 2 Screening, diagnostic criteria and management recommendations for pediatric type 2 diabetes

From: The quality of clinical practice guidelines for management of pediatric type 2 diabetes mellitus: a systematic review using the AGREE II instrument

Guideline characteristics

Treatment recommendations

Organization

Year

Country

Criteria for screening

Frequency of screening

Recommended screening tests

Diagnostic criteria

Recommendation of healthcare delivery

Brazilian Diabetes Society

2015/2016

Brazil

The diagnosis of T2DM in childhood should be made taking into account clinical criteria such as age and sex of the patient, obesity and positive family history for T2DM. Following these criteria, doubtful cases, especially those with initial ketoacidosis should be evaluated further. Due to high miscegenation in Brazil, there are no data to consider race as a risk factor. However, this guideline also lists the ADA recommendations: Screening for DM2 in childhood, should include every obese child with BMI greater than the 85th percentile for age and gender, or weight greater than 120% of the ideal weight for height, presenting with two or more of the following risk factors: (1) positive family history for DM2 in first or second degree relatives; (2) Certain ethnic backgrounds (American Indians, African Americans, Hispanics, Asian/ Pacific Islander); (3) IR signals or conditions associated with IR (AN, hypertension, dyslipidemia, Polycystic ovary syndrome.

Every 2 years, beginning after the age of 10

-RPG, FPG, OGTT

-Evaluation of beta cell function by C-peptide

-The detection of markers of pancreatic islet autoimmunity using autoantibodies including anti-GAD, Anti-IA2, ICA and IAA.

Consider the diagnosis of T2DM in 10–18 year old patients with the following criteria:

• Overweight or obesity (respectively for gender and age with BMI percentile ≥ 85th percentile)

• Strong family history of T2DM

• Substantial residual capacity of insulin secretion

Diagnosis (proven by normal or high concentration of

insulin and C-peptide)

• Insidious onset of disease

• IR (clinical evidence of PCOS and NAFLD)

• Exclusion of autoimmune diabetes (autoantibodies typically associated with type 1 diabetes are not detected).

• the diagnosis is defined biochemically as:

-Fasting glycemia (defined as absence of caloric intake during a minimum period of 8 h) ≥ 126 mg/ dL (≥ 7.0 mmol/L)

• Plasma glucose on OGTT at 2 h post challenge of ≥200 mg / dL (≥ 11.1 mmol/L), and the test is carried out in accordance with WHO recommendation, using Glucose solution containing 75 g of anhydrous glucose Diluted in water

• Random plasma glucose ≥ 200 mg /dL (≥ 11.1 mmol/L), with typical symptoms of hyperglycemia (polyuria, polydipsia, loss of weight).

Physical activity: Children and adolescents with T2DM Should be encouraged to perform moderate to intense physical activity for at least 60 min daily.

Diet: In the diet recommendation for children with T2DM, or at the time of or during treatment, using recommendations of the Academy of Nutrition Pediatric Weight Management Practice Guidelines

Screen time: Non-academic (e.g., television, video games) is limited to 2 h/day

Addressing psychosocial needs: Not reported

Medical and surgical therapies: Metformin should be the drug of first choice for young people and adolescents at the time of diagnosis and beyond, but to be combined with lifestyle modification, including nutritional guidance and physical activity. Introduction of insulin treatment should be done in children and adolescents who have ketosis or diabetic ketoacidosis, in patients in whom distinction between type 1 diabetes versus T2DM is not clear, and where T2DM patients present with random plasma glucose or venous value ≥ 250 mg/dL (> 13.9 mmol/L) or

HbA1c > 9%.

Target HbA1c: < 7%; if not obtained, it is recommended to intensify the treatment.

Diabetes Canada

2018

Canada

Risk factors for the development of type 2 diabetes in children

include a history of type 2 diabetes in a first- or second-degree relative, being a member of a high-risk population (e.g., people of African, Arab, Asian, Hispanic, Indigenous or South Asian descent), obesity, impaired glucose tolerance, polycystic ovary syndrome (PCOS), exposure to diabetes in utero, acanthosis nigricans, hypertension, dyslipidemia, and NAFLD.

Every 2 years

(In Indigenous children, this should begin at 10 years of age or with puberty, whichever sooner)

Use a combination of an A1C and a FPG or random plasma glucose in children and adolescents with any of the following conditions

(three or more risk factors in non-pubertal or two or more risk factors in pubertal children):

• Obesity (BMI ≥ 95th percentile for age and gender)

• Member of a high-risk ethnic group (e.g., African, Arab, Asian, Hispanic, Indigenous or South Asian descent)

• Family history of T2DM and/or exposure to hyperglycemia in utero

• Signs or symptoms of IR(including acanthosis nigricans, hypertension, dyslipidemia, PCOS and NAFLD [ALT >3× upper limit of normal or fatty liver on ultrasound))

• Impaired fasting glucose or impaired glucose tolerance

• Use of atypical antipsychotic medications

If there is a discrepancy between the A1C and FPG or random plasma glucose, testing may be repeated or a 2-h OGTT (1.75 g/kg; maximum 75 g) may be performed

-OGTT (1.75 g/kg anhydrous glucose; maximum 75 g) may be used as a screening test in very obese children (BMI ≥99th percentile for age and gender) or those with multiple risk factors

-Fasting glycemia defined as FPG of ≥ 126 mg/dL (≥  7.0 mmol/L)

-Plasma glucose on OGTT at 2 h post challenge of ≥  200 mg/dL (≥ 11.1 mmol/L),

-Random plasma glucose ≥ 200 mg/ dL (≥ 11.1 mmol/L) with typical symptoms of hyperglycemia (polyuria, polydipsia, Loss of weight).

Physical activity: Recommend (in the absence of direct evidence for this population) that children strive to achieve the same activity level recommended for children in general: 60 min daily of moderate-to vigorous physical activity

Diet: Not reported

Screen time: Limiting screen time to 2 h/day

Psychosocial issues: Psychological issues, such as depression, binge eating and smoking cessation, need to be addressed and interventions offered.

Medical and surgical therapies: Insulin is required in those with severe metabolic decompensation at diagnosis (e.g., DKA, HbA1c of ≥ 9.0%, symptoms of hyperglycemia) but may be successfully weaned once glycemic targets are achieved, particularly if lifestyle changes are effectively adopted. Metformin has been shown to be safe in adolescents for up to 16 weeks, reducing HbA1c by 1.0–2.0% and lowering FPG. Side effects are similar to those seen in adults. Glimepiride has also been shown to be safe and effective in adolescents for up to 24 weeks. The experience of bariatric surgery in adolescents with type 2 diabetes is very limited with specific eligibility criteria (BMI > 35 kg/m2, Tanner stage IV-V, and skeletal maturity).

Target HbA1c: ≤ 7%

German Diabetes Association (Deutsche Diabetes Gesellschaft)

2015

Germany

All overweight children (BMI > 90th percentile) age 10 years or older who have two or more risk factors:

• A close blood relation has type 2 diabetes

• Membership of a group with elevated risk (e. g. East Asians, Afro-Americans, Hispanics)

• Extreme obesity (BMI > 99.5th Percentile)

• Signs of IR or of changes associated with it (arterial hypertension, dyslipidemia, elevated transaminases, PCOS, AN).

Not reported

FPG, RPG, OGTT

-Fasting glucose: ≥126 mg/dL (≥ 7.0 mmol/L),

-OGTT: 2-h level ≥ 200 mg/dL (≥11.1 mmol/L). if patient asymptomatic, repeat the test

-Indications for distinguishing between type 2 and type 1 diabetes can improve by the following additional laboratory tests:

• C-peptide

• Autoantibodies (GAD, IA2, ICA, IAA)

Physical activity: Not reported

Diet: Not reported

Screen time: Not reported

Psychosocial issues: Particularly in adolescents, to look for signs of eating disorders and affective disorders (anxiety, depression). If there is a psychiatric disorder, a psychiatrist or psychologist should be consulted

Medical and surgical therapies:

If initial HbA1c is ≥9% with blood glucose ≥250 mg/dL (≥13.9 mmol/L) and if signs of absolute insulin deficiency, initial insulin therapy is recommended.

-Oral hypoglycemic agents have to be used when glycemic control by lifestyle intervention proves to be insufficient. Metformin ± insulin is needed.

Target HbA1c: < 7%.

In addition, treatment aim is to achieve a fasting glucose level under 126 mg/dL (< 7.0 mmol/L)

Hellenic Diabetes Federation

2013

Greece

Not reported for children. Some criteria that may apply to children:

• Waist circumference ≥ 102 cm (male) and ≥ 88 cm (female)

• Body mass index ≥ 30 kg/m2

• Family history of diabetes in parents, siblings, children

• History of hypertension

• History of gestational diabetes

• Polycystic ovarian syndrome

Not reported for children. For adults, if normal FPG, recheck every 3 years

FPG, RPG, OGTT

FPG of ≥126 mg/dL (≥ 7.0 mmol/L)

-Plasma glucose on OGTT at 2 h post challenge of ≥ 200 mg/dL (≥ 11.1 mmol/L),

-Random plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) with symptoms

Physical activity: 30 min of exercise 5 times a week

Diet: Managing carbohydrate intake

Screen time: Not reported

Psychosocial issues: Not reported

Medical and surgical therapies:

Immediate initiation of insulin if there is significant hyperglycemia, metabolic deregulation, and hyperketonemia.

• Metformin

• Sulfonylureas in teens may be tried if metformin is not effective

Target HbA1c: < 7.5% in children, ≤ 7.0% in teens

Associazione Medici Diabetologi/Societa Italiana di Diabetologia

2016

Italy

-At-risk children with BMI between the 85th–95th percentile:

-Positive family history of T2DM -Early cardiovascular disease in family

-AN

-Hypertension

-Dyslipidemia

-PCOS

-Children with BMI ≥ 95th percentile

Distinction between type 1 versus type 2 diabetes can be difficult and may need to be based on the presence of autoantibodies,

C-peptide and insulin levels

Not reported

- FPG, RPG, OGTT

-HbA1c recommended, however the screening section is not reporting on the non-use of HbA1c in pediatric populations

-Fasting glycemia defined as FPG of ≥ 126 mg/dL (≥ 7.0 mmol/L)

-Plasma glucose on OGTT at 2 h post challenge of ≥ 200 mg/ dL (≥ 11.1 mmol/L),

-Random plasma glucose ≥ 200 mg/ dL (≥ 11.1 mmol/L) with typical symptoms of hyperglycemia. If asymptomatic, to repeat testing on a separate day

Using ADA recommendations for lifestyle management

Medical and surgical therapies: Metformin is the drug of choice for diabetes type 2 without ketosis in diabetic adolescents. Insulin therapy should be initiated in case of marked hyperglycemia with ketosis. There is no indication for the use of sulfonylureas in pediatric patients.

Target HbA1c: Not specifically reported, assumed to follow ADA recommendations

Japan Diabetes Society

2013

Japan

Not reported

Not reported

-FPG, RPG, OGTT

-HbA1c recommended, however the screening section is not reporting on the non-use of HbA1c in pediatric populations

Fasting glycemia defined as FPG of ≥ 126 mg/dL (≥ 7.0 mmol/L)

-Plasma glucose on OGTT at 2 h post challenge of ≥ 200 mg/ dL (≥ 11.1 mmol/L),

-Random plasma glucose ≥ 200 mg/ dL (≥ 11.1 mmol/L) with typical symptoms of hyperglycemia

Physical activity: Every effort should be made to increase physical activity levels and energy expenditure in pediatric/adolescent patients to improve IR.

Diet: Recommendations are aimed at providing patients with necessary and sufficient energy for normal development and growth, adjusted by age and sex. In obese patients, the amount of energy intake should be adjusted to 90–95% of the energy required for ideal body weight.

Screen time: Not reported

Psychosocial issues: Not reported

Medical and surgical therapies: In patients who are not insulin-dependent and whose glycemic goals cannot be achieved with diet/exercise therapy alone within 2–3 months, oral glucose-lowering agents should be initiated. In patients with ketoacidosis or those in whose adequate glycemic control cannot be achieved with oral hypoglycemic agents, insulin therapy should be used. Patients should also be treated for hypertension, dyslipidemia and other comorbidities

Target HbA1c: < 7%

Latvijas Diabēta Asociācija/Latvijas Endokrinologu Asociācija

2007

Latvia

BMI with regards to age and gender is > 85% and two of the following risk factors:

-Family history of first or second degree relatives with T2DM

-Populations with increased risk (e.g., African-Americans, American Indians, Asian and Pacific Islander population)

-Any of the following symptoms of IR: AN, dyslipidemia, or PCOS

10 years or at the beginning of puberty whichever sooner, then every 2 years

FPG, RPG, OGTT.

Diagnosis of T2DM if random glucose ≥11.1 mmol/l or glucose level 2 h post OGTT ≥ 11.1 mmol/l.

If fasting blood glucose on two repeat tests ≥7.0 mmol/l

Physical activity: At least 15–30 min a day.

Diet: Total daily caloric based the age and body weight

Screen time: Not reported

Psychosocial issues: Not reported

Medical and surgical therapies:

• Metformin is the first drug of choice (maximum dose of 2000 mg/day)

• Insulin therapy, using appropriate insulin regimen.

• If the fasting glucose > 270 mg/dL (> 15 mmol/L), ketosis or ketoacidosis, and HbA1c > 9%, then use insulin ± metformin.

• If there is diabetic ketosis, but HbA1c 7–9%, then treatment with metformin and suggest to follow diet recommendations as well as regular physical activity. Recommend clinic visits every 3 months to determine the HbA1c. If HbA1c is > 7% after 6 months of treatment, to begin insulin therapy.

• If HbA1c is < 7%, then suggest to follow diet and physical activity recommendations. If, after 3 months of non-pharmacological treatment HbA1c > 7%, use metformin.

Target HbA1c: ≤ 7.5% for 6–12 years of age

≤  6.5% in children over 12 years of age

Diabetasgaires

2014

Lithuania

Reference criteria from International Diabetes Federation

Not reported

-Pancreatic autoantibodies should be tested for autoimmunity in suspected cases of T2DM to clarify the diagnosis

-Pancreatic antibodies should be tested for all obese / overweight children > 13 years, when suspicion of clinical type 1 diabetes (weight loss, ketosis / ketoacidosis)

-With T2DM diagnosis, it is recommended to measure blood pressure, fasting lipids, test urine for microalbuminuria and do dilated eye exam to examine the retina. Monitoring and treatment guidelines for hypertension, dyslipidemia, microalbuminuria and retinopathy are the same as type 1 diabetes. Specific problems such as PCOS, and various diseases associated with obesity, such as sleep apnea, NAFLD, Orthopedic complications and psychosocial problems must be also tested for.

Diabetes mellitus is diagnosed by detecting at least one of the criteria:

FPG ≥ 7.0 mmol/L and/or blood glucose 2 h post 75 g of glucose ≥ 200 mg/dL (≥ 11.1 mmol/L). Test for pancreatic antibodies recommended

Physical activity: Recommended lifestyle changes,

no further details

Diet: Recommended lifestyle including nutritional changes, no further details

Screen time: Not reported

Psychosocial issues: Not reported

Medical and surgical therapies: Metabolically stable patients first-line drug is metformin (approved the use for those 10 years and older). If within 3 months failed to reduce or maintain HbA1c < 7% to treat with insulin. In the beginning, in the presence of metabolic instability, it may be necessary to start treatment with insulin

Target HbA1c: < 7%

Malaysian Ministry of Health

2015

Malaysia

-Symptomatic individuals should be screened for diabetes

Asymptomatic individuals should be screened if they are

-Overweight (BMI > 85th percentile for age and sex, or weight > 120% of ideal body weight)

and

Have two or more of the following risk factors:

-Family history of T2DM in first- or second-degree relatives.

-Signs and conditions associated with IR (AN, hypertension, dyslipidemia, PCOS).

-Maternal history of gestational diabetes

Initiated at 10 years of age or at onset of puberty, whichever sooner

Fasting insulin and C-peptide has been used to aid in the diagnosis. However, their measurement should be interpreted with caution due to considerable overlap between type 1 diabetes, T2DM and monogenic diabetes at onset and within 2 years of diagnosis.

FPG, OGTT, Random blood glucose

In symptomatic individual, one abnormal glucose value is diagnostic. In asymptomatic individual, two abnormal glucose values are required.

Diagnostic values: venous blood samples demonstrating

• FPG ≥ 7.0 mmol/L

• Random or 2 h post OGTT plasma glucose ≥ 11.1 mmol/L.

Physical activity: 150 min per week and/or at least 90 min/week of vigorous aerobic plus at least two sessions per week of resistance exercise

Diet: Nutrition recommendations following the adult guidelines:

-Total carbohydrate intake should be measured to help the patient understand content

-Fat content should be 25–35% of daily intake

-Protein intake 15–20% of daily intake

Screen time: Not reported

Psychosocial issues: Regular screening for eating disorders and depression

Medical and surgical therapies: Among all the drugs currently used to treat T2DM in adults, only metformin and insulin are FDA approved for use in adolescents. Metformin should be started with 500 mg daily for 7 days. Gradual dose increment by 500 mg once a week over 3–4 weeks until the maximal dose of 1000 mg twice daily.

Insulin may be required for initial metabolic control. Transition from insulin to metformin can usually be made when metabolic stability is reached. This may take 2–6 weeks. Long-acting or intermediate acting insulin may be added at a dose of 0.5 units/kg/day, but can be increased to achieve glycemic targets.

Target HbA1c: < 6.5%

Netherlands Diabetes Federation

2015

Netherlands

In the Netherlands, no systematic screening is done.

Screening criteria are not applicable since systematic screening is not recommended.

Screening tests are not applicable since systematic screening is not recommended.

Fasting glucose: ≥ 126 mg/dL (≥ 7.0 mmol/L),

-OGTT: 2-h level ≥ 200 mg/dL (≥ 11.1 mmol/L). if patient asymptomatic, repeat the test

Physical activity: Recommend 60 min/day of moderately vigorous physical activity. Intensive lifestyle programs with professional guidance in the areas of nutrition therapy, exercise and behavioral change in the treatment of overweight/obesity is preferred.

Diet: Advise is blended for type 1 and type 2 diabetes.

Counsel patients to reduce the intake of refined carbohydrates and sweetened drinks. Suggest individualized carbohydrate intake, and to avoid elimination of food items to curb the risk of eating disorders.

Fat intake should be defined as per healthy age-based intake recommendations. The use of plant sterols in children over 5 years is acceptable if LDL is elevated.

For children with diabetes, there is not enough evidence to recommend an ideal amount of protein for optimizing glucose and improving cardiovascular risk.

Micronutrients The recommendation for vitamins, minerals and trace elements for children with diabetes is the same as for healthy children. Vitamin D supplementation is necessary in young children

It is recommended that wherever possible, to replace processed products by unprocessed products.

Screen time: Not reported

Psychosocial issues: Not reported specifically, but encourages the focus on a positive body image and to avoid food restrictions to prevent eating disorders. Nutritional advice should be discussed with the whole family and tailored to the child’s cultural and individual needs.

Medical and surgical therapies: lifestyle intervention with insulin therapy

Target HbA1c: ≤ 7%

Polskiego Towarzystwa

Diabetologicznego

2015

Poland

Obese children above 10 years of age or puberty, whichever is earlier (BMI > 95%)

Every 2 years in children > 10 years

Random blood glucose, FPG, or OGTT

• FPG ≥ 7.0 mmol/l; or

• Venous plasma glucose ≥ 11.1 mmol/L (≥ 200 mg/dl) at 2 h after a 75 g OGTT or random measurement

if symptomatic

-If asymptomatic, or symptomatic but blood glucose < 200 mg/dL

(< 11.1 mmol/L) needs two tests to establish the diagnosis at different times

Physical activity: Moderate physical activity > 60 min/day

Diet: Maintain proper balance of calories and gradual reduction of carbohydrates, up to 45–50% daily caloric intake; restrict sugars up to 10% daily caloric requirement

Screen time: Not reported

Psychosocial issues: Provide psychological care with children with diabetes and their families with support; screening for depression and eating disorders should be performed in all patients at 1–2 years intervals

Medical and surgical therapies: Treatment of choice is metformin and/or insulin; if HbA1c < 9, and no symptoms of disease or acidosis, metformin; should be used. If symptomatic, give metformin and basal insulin. If ketotic, start insulin similar to type 1 diabetes (short and intermediate or long acting insulin)

Target HbA1c: ≤6.5%

Scottish Intercollegiate Guidelines Network*

Updated 2017

Scotland

Not reported

Not reported

FPG, OGTT

The clinical diagnosis of diabetes is often indicated by the presence of symptoms such as polyuria, polydipsia, and unexplained weight loss, and is confirmed by measurement of hyperglycemia.

• FPG ≥ 7.0 mmol/l; or

• Venous plasma glucose ≥ 11.1 mmol/L (≥ 200 mg/dl) at 2 h after a 75 g OGTT

Physical activity: People with type 2 diabetes should be encouraged to participate in physical activity or structured exercise to improve glycemic control and cardiovascular risk factors. Exercise and physical activity (involving aerobic and/or resistance exercise) should be performed on a regular basis.

Diet: Structured education program are recommended.

Screen time: Not reported

Psychosocial issues: Children should be offered psychological

interventions (motivational interviewing, goal setting skills and Cognitive Behavioral Therapy) to improve glycemic control

Medical and surgical therapies: Metformin and insulin therapy are the mainstay of treatment.

Target HbA1c: 7% is reasonable to reduce risk of microvascular disease and macrovascular disease; a target of 6.5% may be appropriate at diagnosis

Singapore Ministry of Health

2014

Singapore

Children and adolescents with suspected diabetes; screening for T2DM in asymptomatic children and adolescents is not recommended

Not reported

FPG, Casual plasma glucose, OGTT

Casual plasma glucose of ≥ 200 mg/dL (≥ 11.1 mmol/L); FPG of ≥126 mg/dL (≥ 7 mmol/L); 2 h post challenge plasma glucose ≥200 mg/dL (≥ 11.1 mmol/L)

Physical activity: Children may initially be treated with lifestyle modification (diet and exercise) unless they are symptomatic or severely hyperglycemic; lifestyle changes in diet and exercise should be recommended for all children with type 2 diabetes mellitus and continued, even after addition of pharmacologic therapy

Diet: Not reported specifically for children

Screen time: Not reported

Psychosocial issues: Psychoeducational interventions recommended

Medical and surgical therapies: Metformin may be started as the first-line oral agent if blood glucose targets are not achieved with lifestyle intervention. Insulin should be started if oral agents fail to attain target control. If monotherapy with metformin over 3–6 months has failed, insulin should be added to the treatment

Target HbA1c: < 7.5%

Endodiab

2016

Slovenia

Obese adolescents BMI > 98th percentile; overweight adolescents BMI > 91st percentile with two additional criteria:

-Presence of T2DM in a relative; −Exposure to gestational diabetes

-Belonging to racial/ethnic groups more likely to have T2DM

-Clinical signs of IR

Every 2–3 years

Random blood glucose, fasting insulin and OGTT

Random blood glucose ≥ 200 mg/dL(> 11.1 mmol/L); Symptoms of diabetes (polyuria, polydipsia, unexplained weight loss) and plasma glucose ≥ 200 mg/dL (> 11.1 mmol/L); FPG ≥ 7 mmol/L glucose levels 2 h post OGTT > 11.1 mmol/l

Physical activity: Begin with the implementation of the program for lifestyle changes including addressing the diet and psychologist

Diet: Not reported specifically for children

Screen time: Not reported

Psychosocial issues: Begin with the implementation of the program for lifestyle changes including addressing the diet and psychologist

Medical and surgical therapies: If HbA1c is < 9%, start with lifestyle intervention and add Metformin. Start with a dose of 500 mg/day, increase by 500 mg/week to a maximum dose of 1000 mg two times a day. If within 3–4 months metformin does not lead to HbA1c < 6.5%, add basal insulin.

-If patients are metabolically unstable or HbA1c > 9%, insulin treatment is needed. If not acidotic, insulin and metformin can start simultaneously. After 2–6 weeks can switch to monotherapy with metformin.

-In overweight adolescents with BMI > 40 kg/m2 who are pubertal and > 15 years old, with failed conservative approach of dietary therapy and physical activity and metformin for more than 6 months, possible treatment of bariatric surgery is considered.

Target HbA1c: < 6.5%

Society for Endocrinology, Metabolism and Diabetes of South Africa

2017

South Africa

Little evidence justifies systematic screening of asymptomatic children for T2DM. However, opportunistic testing should be considered in overweight patients (BMI ≥ 85%) who satisfy at least 2 of the following criteria:

-Family history of T2DM in first or second degree relative

-High risk ethnicity

-Signs or conditions associated with IR

-If BMI ≥ 99th percentile

Initial screening may begin at 10 years or at onset of puberty, whichever occurs earlier, and should be performed every 2 years

FPG is preferred, but if borderline do OGTT. Symptoms of diabetes and a fasting or random plasma glucose

OGTT 2 h post-challenge plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L); or FPG ≥ 126 mg/dL (≥ 7.0 mmol/L); or random plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L);

HbA1c ≥ 6.5%

Physical activity: The aim is to increased exercise capacity

Diet: Not reported

Screen time: Not reported

Psychosocial issues: Not reported

Medical and surgical therapies: Treat with insulin if patient presents with ketosis, acidosis and dehydration. Metformin can be added later with a 500 mg daily dose at first, and then increase to a maximum dose of 1000 mg twice daily over 3–4 weeks.

In an otherwise well, less symptomatic child, metformin is the treatment of choice

Target HbA1c: < 7%

Diabetes Association of Thailand

2014

Thailand

Children and adolescents aged 10 years and over who are obese and have 2 risk factors out of the following:

-Have parents or siblings with diabetes

-Have high blood pressure (BP ≥ 130/85 mmHg)

-Acanthosis nigricans

Start screening at ≥ 10 years

FPG, random plasma glucose, OGTT

Symptomatic or asymptomatic blood glucose levels ≥ 200 mg/dL (≥ 11.1 mmol/L); OGTT 2-h plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L); FPG ≥ 126 mg/dL (≥ 7.0 mmol/L)

Physical activity: General recommendation for exercise.

Diet: Determine food and energy requirements by age; food consists 50–60% carbohydrates, 25–30% fat and 15–20% protein; sweetened drinks should be less than 5% and should be consumed with high fiber foods; suggest eating more vegetable fats than animal fat.

Screen time: Not reported

Psychosocial issues: Build understanding and self-care experience; practice and help with psychological adjustment for patients and parents; provide support, adaptation, and family preparedness

Medical and surgical therapies: Aim for weight loss of 5–10%. Insulin therapy if HbA1c is > 9% or blood glucose ≥11.1 mmol/L. with improvement, start metformin 250 mg daily for 3–4 days, then increased within 3–4 weeks, max amount 1000 mg twice per day. Reduce insulin by 10–20% each time metformin was adjusted up to target and then discontinue insulin, most take 2–6 weeks to stop the insulin injection.

Target HbA1c: < 7.5%

National Institute for Health and Care Excellence

Updated 2016

United Kingdom

Consider T2DM in children and young people with the following risk factors:

-Strong family history of type 2 diabetes

-Obese at presentation

-Black or Asian family origin

-Have no insulin requirement, or have an insulin requirement of less than 0.5 units/kg/day after the partial remission phase

-Show evidence of insulin resistance (for example, acanthosis nigricans)

Not reported

Random plasma glucose test, FPG, OGTT

OGTT is not usually necessary or appropriate for children and young people who present with symptoms (thirst, polydipsia (increased drinking), polyuria (increased urine output), recurrent infections and weight loss, hyperglycemia, marked glycosuria and ketonuria).

Random plasma glucose concentration ≥ 200 mg/dL (≥ 11.1 mmol/L); or FPG ≥ 126 mg/dL (≥ 7.0 mmol/L); or random plasma glucose concentration ≥ 200 mg/dL (≥ 11.1 mmol/L) post OGTT

Physical activity: Advise children or young persons who are overweight or obese about the benefits of physical activity and weight loss, and provide support towards achieving this

Diet: Explain to child or young person and their family members or carers how healthy eating can help to reduce hyperglycemia and cardiovascular risk, and promote weight loss; provide dietary advice in a sensitive manner, taking into account the difficulties that many people encounter with weight reduction, and emphasize the advantages of healthy eating for blood glucose control and avoiding complications. To take into account social and cultural considerations when providing advice on dietary management. Encourage people with type 2 diabetes to eat at least 5 portions of fruit and vegetables each day

Screen time: Not reported

Psychosocial issues: Diabetes teams should be aware that children and young people with T2DM have a greater risk of emotional and behavioral difficulties; offer emotional support after diagnosis; offer timely and ongoing access to mental health professionals with an understanding of diabetes because they may experience psychological problems or psychosocial difficulties that can impact the management of diabetes and wellbeing; offer screening for anxiety and depression to children and young people who have persistently suboptimal glycemic control

Medical and surgical therapies: Offer metformin from diagnosis; offer bariatric surgery in centers that have dedicated pediatric facilities for children and young people with diabetes; all centers should have written protocols on safe surgery for children and young people.

Target HbA1c: ≤6.5%

American Diabetes Association

2016

United States

Children and adolescents who are overweight or obese and who have two or more of the following risk factors for diabetes:

-Family history of type 2 diabetes in first- or second-degree relative

-Race/ethnicity (Native American, African American, Latino, Asian American, Pacific Islander)

-Conditions associated with insulin resistance (acanthosis

nigricans, hypertension, dyslipidemia, PCOS, or small-for-gestational age)

-Maternal history of diabetes

3 year intervals beginning at 10 years or onset of puberty, whichever is earlier

Random plasma glucose, FPG and OGTT

Fasting plasma glucose ≥126 mg/dL (≥ 7.0 mmol/L); or 2 h post OGTT plasma glucose ≥200 mg/dL (≥ 11.1 mmol/L); or random plasma glucose ≥200 mg/dL (≥ 11.1 mmol/L)

Physical activity: To exercise regularly and maintain a healthy weight

Diet: Eat a balanced diet; nutrition recommendations should be culturally appropriate and sensitive to family resources

Screen time: Not reported

Psychosocial issues: Not reported

Medical and surgical therapies: Presentation with ketosis or ketoacidosis requires a period of insulin therapy until fasting and postprandial glycemia have been restored to normal or near-normal; insulin is used if HbA1c is > 9% or if blood glucose levels are > 250 mg/dL (13.9 mmol/L). Metformin therapy may be used after resolution of ketosis/ketoacidosis or in stable patients at diagnosis.

Target HbA1c: < 7.5%

American Academy of Pediatrics

2013

United States

Overweight or obesity; strong family history of T2DM; the presence of IR

Not reported

HbA1c test (not alone), fasting plasma glucose test, oral glucose tolerance test, random plasma glucose test

HbA1c ≥6.5%; fasting plasma glucose ≥ 126 mg/dL; or 2 h plasma glucose OGTT ≥ 200 mg/dL (≥ 11.1 mmol/L); or random plasma glucose ≥ 200 mg/dL (≥11.1 mmol/L) with symptoms

Physical activity: Clinicians should initiate a lifestyle modification program, including nutrition and physical activity. Recommend engagement in moderate-to-vigorous exercise for at least 60 min daily

Diet: Not reported

Screen time: Limit non-academic screen time to less than 2 h a day

Psychosocial issues: Not reported

Medical and surgical therapies: Insulin is used if HbA1c is > 9% or if blood glucose levels are > 250 mg/dL (13.9 mmol/L). Start metformin as first-line therapy for children and adolescents at the time of diagnosis with lifestyle intervention.

Target HbA1c: < 7.0%

International Society for Pediatric and Adolescent Diabetes (ISPAD)

2014

International

Obese at-risk youth

Not reported

Tests for fasting plasma glucose, OGTT, or casual plasma glucose

Diagnosis can be made based on fasting glucose, 2-h post challenge glucose, or HbA1c; in the absence of symptoms, testing should be confirmed on a different day; fasting plasma glucose of ≥ 126 mg/dL (≥ 7 mmol/L), or 2 h-post challenge plasma glucose of ≥ 200 mg/dL (11.1 mmol/L); or casual plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L); or HbA1c > 6.5% (not alone, use in diagnosis of T2DM is controversial)

Physical activity: Lifestyle change should be initiated at the time of diagnosis of T2DM; increased physical activity to at least 60 min per day of moderate-to-vigorous activities. Activity prescriptions should be developed and should be sensitive to family environment and resources.

Diet: Reduced carbohydrate and fat intake, increased fruit and vegetable intake, elimination of sugar-sweetened beverages and juice, reduce intake of processed and prepackaged foods, reduce intake of foods with refined sugars, reduce eating out.

Change recommended in eating behaviors.

Screen time: Reduction in sedentary time including TV, computer related activities, texting, and video games, screen time limited to < 2 h/day

Psychosocial issues: Should be assessed for depression; identified patients should be referred to appropriate mental healthcare providers experienced in addressing depression in youth

Medical and surgical therapies: Initial pharmacologic treatment should include metformin and insulin alone or in combination; for metformin, begin with 500 mg daily for 1 week, and titrate by 500 mg once a week over 3–4 week to the maximal dose of 1000 mg twice-daily. Patients who are not metabolically stable require insulin, and if patient fails to reach target HbA1c of < 6.5% within 3–4 months on metformin monotherapy.

Bariatric surgery for those who have been unsuccessful with medical therapy alone, but should be done in centers with expertise in this procedure.

Target HbA1c: < 6.5%

International Diabetes Federation (IDF) & International Society for Pediatric and Adolescent Diabetes (ISPAD)

2011

International

Overweight/obese children > 13 years of age

Not reported

Two abnormal glucose values on OGTT are diagnostic of diabetes on two separate days in asymptomatic individuals

Fasting plasma glucose of ≥126 mg/dL (≥ 7 mmol/L). Casual or 2 h-post challenge plasma glucose of ≥ 200 mg/dL (11.1 mmol/L); or HbA1c > 6.5% (not alone)

Mainly based on ISPAD guidelines

Physical activity: Lifestyle changes in diet and exercise are essential to increase insulin sensitivity

Diet: Plan should be adapted to cognitive and psychological needs of the child as well as the family’s cultural, ethnic and family traditions

Screen time: Not reported

Psychosocial issues: Mental health professionals are needed to support the patient and families.

Medical and surgical therapies: Metformin – begin with 250 mg daily for 3–4 days, if tolerated increase to 250 mg twice a day, titrate up to a maximal dose of 1000 mg twice a day.

Use insulin if needed.

Bariatric surgery for adolescents with obesity related co-morbidities, including type 2 diabetes may be considered. This procedure should be performed in a center with an established program collecting outcome data..

Target HbA1c: < 7%

  1. IR insulin resistance, AN Acanthosis nigricans, BMI Body mass index, ICA Islet cell antibodies, GAD anti Glutamic Acid Decarboxylase antibodies, IA2 Islet Antigen 2 antibodies, ICA Islet Cell Antibodies, IAA Insulin Autoantibodies, RPG Random Plasma Glucose, FPG Fasting Plasma Glucose, PCOS polycystic ovary syndrome, ALT Alanine aminotransferase, HbA1c Glycated hemoglobin, DKA diabetic ketoacidosis, OGTT Oral glucose tolerance test, NAFLD Non-alcoholic fatty liver disease, ADA American Diabetes Association
  2. *While this paper was under review, a new version of SIGN guidelines was published in November 2017. For the sake of completeness, we used this latest version of the guidelines to report here. In addition, SIGN have published another document specifically reporting the pharmacotherapeutic options for treating T2DM that was referenced in the updated guideline. This latter document was consulted while compiling the recommendations for health care delivery