Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines

GRADE definition and NHMRC levels of evidence

A

B

C

D

Excellent

Good

Satisfactory

Poor

Definition

Body of evidence can be trusted to guide practice

Body of evidence can be trusted to guide practice in most situations

Body of evidence provides some support for recommendations but care should be taken in its application

Body of evidence is weak and recommendation should be applied with caution

Evidence base

Several level I or II studies with low risk of bias

One or more level II studies with low risk of bias

Level III studies with low risk of bias, or level II studies with moderate risk of bias

Level IV studies or level I to III with high risk of bias

Consistency

All studies consistent

Most studies consistent and inconsistencies may be explained

Some inconsistency reflecting genuine uncertainty around clinical question

Evidence is inconsistent

Clinical impact

Very large

Substantial

Moderate

Slight or restricted

Generalisability

Populations studied in body of evidence are the same as the target population for the guideline

Populations studied in body of evidence are similar to the target population for the guideline

Populations studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population

Populations studied in body of evidence differ from target population and it is hard to judge whether it is sensible to generalise to target population

Applicability

Directly applicable to Australian health care context

Applicable to Australian health care context with few caveats

Probably applicable to Australian health care context with some caveats

Not applicable to Australia health care context

GRADE quality of evidence and definition

High quality. Further research is unlikely to change our confidence in the estimate of effect

Moderate quality. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate

Low quality. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate

Very low quality. Any estimate of effect is very uncertain

Guidelines sections and subsections

Recommendations

GRADE category

Screening diagnosis

• maternal history of diabetes, including gestational diabetes during the child's gestation;
• first degree relative with type 2 diabetes;
• race or ethnicity (South Asian, South East Asian, Middle Eastern, North African and Latino) — for Indigenous populations: Aboriginal, Torres Strait Islander, Māori and Pacific Islander (see section below on considerations for children and adolescents of Indigenous backgrounds in Australasia);
• signs of insulin resistance (acanthosis nigricans);
• other conditions associated with obesity and metabolic syndrome (ie, hypertension, dyslipidaemia, fatty liver disease, polycystic ovary syndrome, small for gestational age); and
• use of psychotropic medications

B

Diagnosis of type 2 diabetes can be made using fasting glucose, 2‐hour glucose level from oral glucose tolerance or HbA_1c tests

B

Diabetes autoantibodies testing (glutamic acid decarboxylase and islet tyrosine phosphatase 2) should be considered in all children and adolescents with clinical phenotype of type 2 diabetes due to higher prevalence of type 1 diabetes mellitus in this age group

B

Genetic testing for monogenic diabetes should be considered if diabetes is present in two or more consecutive generations and diabetes autoantibodies are negative

B

Diabetes education

All children and adolescents with type 2 diabetes need comprehensive and specific diabetes self‐management education that is family‐centred, individualised, and developmentally and culturally appropriate

B

Education should be delivered by a specialised multidisciplinary team with expertise in managing paediatric type 2 diabetes

C

Monitoring glycaemia

Self‐monitoring of blood glucose needs to be individualised according to treatment type and need to improve glycaemia

D

Aim for blood glucose levels 4–6 mmol/L (fasting) and 4–8 mmol/L (2 hours postprandial)

D

Target HbA_1c levels should be ≤ 48 mmol/mol (≤ 6.5%) given the significant morbidity and mortality, but without causing hypoglycaemia and/or undue treatment burden

C

HbA_1c should be assessed every 3 months

D

Healthy lifestyle

Weight management and multicomponent approach to lifestyle modification is required at diagnosis and ongoing

C

    Weight management

Optimise weight management

B

    Diet

Aim for healthy eating: eliminate sugar‐sweetened beverages, reduce calorie‐dense and nutrient‐poor foods, provide education regarding carbohydrates (role, sources, portion control and, if appropriate, counting of carbohydrates) and ensure adequate intake of nutrient‐dense and low glycaemic index foods

B

Reduce total energy intake to achieve ≥ 7% decrease in excess weight

B

    Physical activity

Aim for at least 60 min/day of moderate to vigorous physical activity to improve body composition, glucose management and insulin sensitivity

B

Exercise programs should include resistance activities to increase muscle mass, contributing to improved blood glucose management

B

    Sedentary behaviour

Recreational screen time should be limited to ≤ 2 hours a day

C

    Sleep

Encourage quality sleep of 8–11 hours duration according to age, with consistent bed and wake‐up times and reduction of electronic media use in the evening

C

Considerations for children and adolescents of Indigenous backgrounds in Australasia (Aboriginal, Torres Strait Islander, Māori and Pacific Islander)

Consider point‐of‐care HbA_1c screening in all Aboriginal and Torres Strait Islander children from 10 years of age (or at onset of puberty, whichever occurs earlier) who have one or more risk factors:

• overweight or obesity (BMI ≥ 85th or ≥ 95th percentile respectively, and/or waist circumference to height ratio > 0.5);
• maternal history of diabetes or gestational diabetes during the child's gestation;
• first degree relative with type 2 diabetes;
• signs of insulin resistance (acanthosis nigricans);
• other conditions associated with obesity and metabolic syndrome (ie, hypertension, dyslipidaemia, fatty liver disease, polycystic ovary syndrome, small for gestational age); and
• use of psychotropic medications

C

Consider provision of health services using non‐traditional locations or structures, with opportunities for young people and families to meet each other and improving engagement with health care professionals*

C

Identify the priorities of the adolescent, avoid blame and stigmatising language, and individualise health messages, empowering adolescents to manage their risk*

C

Pharmacotherapy

Metformin up to 2 g per day should be used as the first line medication in patients presenting with mild symptoms or in those who are diagnosed after screening

A

Insulin should be the first line treatment for patients who present with diabetes ketoacidosis, hyperglycaemic hyperosmolar state or ketosis, and should be added to metformin where glycaemic targets have not been achieved or maintained with metformin monotherapy

B

If glycaemic targets are not achieved with metformin (with or without insulin), other glucose‐lowering medications approved for adults should be considered. Such medications should only be prescribed under the guidance of a paediatric endocrinologist, given limited evidence for safety and efficacy in children and adolescents

D

Complications and comorbidities

Screen for all complications and comorbidities soon after diagnosis of type 2 diabetes to establish prompt management and ongoing assessment and management^†

A

    Retinopathy

Assess retina using dilated pupil exam or retinal photography by an optometrist or ophthalmologist at diagnosis and yearly unless abnormal^†

A

    Nephropathy

Assess early morning urine albumin to creatinine ratio at diagnosis and yearly unless abnormal^†

A

    Neuropathy

Foot examination at diagnosis and yearly unless abnormal^†

C

    Overweight/obesity

Optimise weight management as well as glycaemia to reduce risk of comorbidities and complications^†

B

Consider bariatric surgery for selected post‐pubertal adolescents with type 2 diabetes with severe obesity, taking into account special considerations in relation to consent, procedure, family support and availability of adequate services^†

C

    Psychosocial

Quick screening tools for psychosocial comorbidities and diabetes distress should be used regularly after diagnosis^†

B

Consider screening for disordered eating behaviour^†

D

    Reproductive health

For adolescent girls, a review of menstrual cycle regularity, symptoms and signs of hyperandrogenism, and need of contraception should be done at every visit, especially if the HbA_1c level is above target or the patient is using teratogenic medications^†

B

    Liver disease

Assess liver function test (aspartate aminotransferase and alanine aminotransferase) at diagnosis and yearly unless abnormal^†

B

    Obstructive sleep apnoea

Evaluate symptoms of obstructive sleep apnoea in children and adolescents with obesity*

C

    Hypertension

Assess blood pressure using appropriate cuff at every visit^†

A

    Lipids

Assess lipid profile when glycaemic targets have been achieved after diagnosis and yearly unless abnormal^†

B

Transition

Transition to adult endocrinologist within a multidisciplinary team due to the severity of disease progression and higher risk of diabetes complications

C

Recommendations

Population (non‐Indigenous children and adolescents)

• maternal history of diabetes or gestational diabetes mellitus during the child's gestation;
• family history of type 2 diabetes in first degree relative;
• race and ethnicity (South Asian, South East Asian, Middle Eastern, North African and Latino);
• signs of insulin resistance (acanthosis nigricans);
• conditions associated with obesity and metabolic syndrome (hypertension, dyslipidaemia, fatty liver disease, polycystic ovary syndrome, or small for gestational age); and
• use of psychotropic medications

Screening method

HbA_1c or OGTT

Screening frequency

Every 2–3 years or earlier if excessive weight gain

Clinical presentation

Percentage of patients

Symptoms, signs and investigations

Asymptomatic

33%

• Boils, thrush
• Positive screening or random testing

Symptomatic

67%

• Polyuria
• Polydipsia
• Weight loss
• Fatigue
• Absent to mild ketosis

Diabetic ketoacidosis

11%

• Kussmaul breathing, vomiting, abdominal pain, drowsiness
• Plasma glucose > 11 mmol/L
• Venous pH < 7.3
• Serum bicarbonate > 15 mmol/L
• Ketosis

Hyperglycaemic hyperosmolar state

2%

• Altered consciousness, seizures
• Plasma glucose > 33.3 mmol/L
• Venous pH > 7.25
• Serum bicarbonate > 15 mmol/L
• Absent to mild ketosis
• Effective serum osmolality > 320 mOsm/kg

Criteria

Diagnosis (glucose measurements)

• Classic symptoms of diabetes or hyperglycaemic crisis and random plasma glucose ≥ 11.1 mmol/L,* or
• Fasting^† plasma glucose ≥ 7.0 mmol/L, or
• 2‐hour plasma glucose ≥ 11.1 mmol during an OGTT,^‡ or
• HbA_1c ≥ 48 mmol/mol (≥ 6.5%)^§

Other investigations at diagnosis

• Consider diabetes autoantibody testing in all paediatric patients with the clinical phenotype of type 2 diabetes due to higher prevalence of type 1 diabetes — GAD and IA2 are the most commonly available. Insulin antibodies and zinc transporter 8 antibodies can also be measured if negative GAD and IA2, and type 1 diabetes is suspected
• Insulin and C‐peptide measurements are not recommended as glucotoxicity and lipotoxicity can acutely affect insulin secretion

Type 1 diabetes

Monogenic diabetes

Key points

Most common cause of diabetes in white children from Australia or New Zealand

Up to 8% of children with type 2 diabetes phenotype have monogenic diabetes13

• population frequency of obesity;
• absence of acanthosis nigricans with or without other characteristics of metabolic syndrome;
• ketosis or DKA at diagnosis in ≥ 25% of cases;
• positive type 1 diabetes autoantibodies (> 90%);^†
• family history of type 1 diabetes in up to 4%^‡,12

• population frequency of obesity;
• absence of acanthosis nigricans with or without other characteristics of metabolic syndrome;
• ketosis in neonatal diabetes, rare in other forms;
• negative diabetes autoantibodies;
• family history of diabetes in 90% of individuals
• mild fasting hyperglycaemia occurs in some forms (eg, MODY2)

Investigations

• GAD and IA2 are the most commonly available
• Insulin antibodies and zinc transporter 8 antibodies can also be measured

• Genetic testing: all children with diabetes diagnosed under 6 months of age or diagnosed at 6–12 months of age with negative autoantibodies
• Paired C‐peptide and glucose 2–5 years after diagnosis may be useful to distinguish MODY from type 1 diabetes and type 2 diabetes

Targets*

Frequency

HbA_1c

≤ 48 mmol/mol (≤ 6.5%)

Every 3 months

Self‐monitoring blood glucose

• Fasting blood glucose levels: 4–6 mmol/L
• 2‐Hour postprandial blood glucose levels: 4–8 mmol/L

• if receiving lifestyle management and/or metformin: fasting, before and 2 hours after a main meal three times a week, unless HbA_1c is unreliable or target HbA_1c is not achieved;
• if taking basal insulin or oral agent with hypoglycaemia risks: fasting and bedtime;
• if receiving multiple daily injections, initiating or changing treatment, or treatment goals not met: at least three times a day (fasting, before and 2 hours after a main meal)
• if unwell: four times a day (fasting, before and 2 hours after one main meal and overnight)
• if showing symptoms of hyper‐ or hypoglycaemia

Ketones testing

Negative in urine or capillary blood (β‐hydroxybutyrate)

If unwell, if showing symptoms or signs of ketosis or DKA, or if there is a history of DKA at diagnosis

Evidence

Dietary interventions

Features

GRADE category

Interventions supported by some evidence

Healthy eating advice with appropriate portions and calories

• Based on the Australian Guide to Healthy Eating and the New Zealand Food and Nutrition Guidelines for Healthy Children and Young People22,23 (aged 2–18 years) with age‐specific dietary recommendations
• Foods are categorised as low, moderate and high calorie to guide intake frequency
• Demonstrated effective modest weight loss in adolescents in the short to medium term

B

Lower GI

• Higher GI foods are replaced with nutritious and lower GI foods (GI < 55) to reduce glycaemic load alongside appropriate total energy intake
• It has demonstrated significant reductions in waist circumference, BMI z‐score, and insulin resistance if combined with appropriate total energy intake
• A lower‐GI diet alone significantly reduces insulin resistance

C

Interventions requiring further evidence regarding long term outcomes

Very low carbohydrate diet

• Typically 20–50 g/day or 5–15% of total calories
• Improves hyperinsulinaemia in adolescents with obesity

C

Very low energy diet

• Typically < 800 kcal and < 50 g carbohydrate per day, aiming to induce ketosis
• Recommended only for short periods (8–12 weeks)
• Can achieve short term rapid weight loss while preserving lean body mass, decreasing BMI and improving HbA_1c levels in adolescents with obesity
• A modified approach, closely supervised by a qualified dietitian, is required to ensure adequate provision of micronutrients
• Prior screening for disordered eating using an age‐appropriate validated tool should be considered

D

Intermittent modified fasting

• Carbohydrate is moderately restricted overall to account for 26–44% of total calories
• Effective in the adult population in terms of weight loss, reduced body fat, improved insulin sensitivity and other risk factors
• Limited evidence is available regarding the use of this strategy in adolescents

D

Strategy

Specific issues to consider

Reasons

Engagement of adolescents, families and communities

Utilise Indigenous/cultural (diabetes) health workers and/or practitioners who are well educated on local cultural knowledge, and ideally also include Indigenous/cultural community members to deliver DSME

Mistrust of non‐Indigenous health workers relates to lack of understanding of the culture and the assignment of blame

Use a yarning approach involving a holistic family‐centred discussion about diabetes using pictures, manikins and collaborative goal setting

Overcome literacy issues and encourage family support

Deliver DSME to all family members within the home, community centre and/or non‐clinical settings

Encourage family and community support

Explain causes of diabetes and how to access safe spaces for physical activity and food security

Decrease guilt and stigma

Connect adolescents with peers

Alleviate the stigma, embarrassment and isolation associated with type 2 diabetes

Identify barriers and empowering factors to self‐management at each visit

Improve engagement

Understand reasons for non‐attendance to clinics and keep working on engagement with increased social and family support

Non‐attendance may not represent lack of concern

Language considerations

Avoid a language of blame and shame when discussing type 2 diabetes

Adolescents from high risk populations, where multiple family members have type 2 diabetes and associated complications, may be ambivalent or apathetic, feeling that having diabetes is inevitable and that little can be done

Keep messages positive, simple, easily understood and targeted to the adolescents and their family, acknowledging their priorities, fears, misconceptions, preferences and beliefs

Low literacy, low health literacy and need of different types of communication. Explanations are needed to overcome myths and misconceptions (eg, insulin use causes kidney failure and need for dialysis)

Use of an interpreter if required but need to maintain confidentiality and ensure all the concerns are raised and addressed appropriately

Overcome language barriers if English is not first language

Whole family approach

Engaging the whole family

Increase the likelihood of the adolescent being able to modify behaviour, and reduce unhelpful reactions of isolation, blame or guilt. It may also benefit the health of the whole family

Social support, particularly from other family members with type 2 diabetes who may influence health advocacy, beliefs and behaviour

Other family members with type 2 diabetes may hinder or help the adolescent

Psychosocial health

Screen for psychosocial health; HEEADDSS framework approach exploring the many domains of young people's lives

Adolescents with type 2 diabetes are at higher risk of mental health issues; these are important in their own right but also associated with increased risk of renal complications

Access to Indigenous/cultural health workers or health professionals from relevant ethnic and community groups

There may be fear of disclosure due to mental health stigma

Food security

Social programs and locally developed cooking and nutrition programs can be useful, illustrating foods that can be prepared from the local store, and at a lower cost than highly processed, energy‐dense and low nutritional value foods

There is limited access to affordable, fresh and healthy food choices in rural or remote settings. Less than 10% of housing in remote Indigenous Australian communities have functioning food preparation space, storage facilities and cooking equipment, limiting capacity for healthy lifestyle management of type 2 diabetes

Social welfare

Offer free transport to appointments and subsidise medications using schemes such as Closing the Gap

This may assist with attendance to appointments and achieve treatment outcomes

Complication/comorbidity

Evaluation at diagnosis and yearly unless abnormal or specified*

Treatment

Treatment goals

Other considerations

Retinopathy

• Dilated pupil exam or retinal photograph with a non‐mydriatic camera by an optometrist or ophthalmologist
• Early stages are asymptomatic

• According to retinal findings by ophthalmologist

• Reduce/stop progression of proliferative retinopathy
• Preservation of vision

• Optimise diabetes and weight management and treatment of dyslipidaemia/hypertension, if present

Nephropathy microalbuminuria

• Proper collection of three early morning urine samples for albumin to creatinine ratio (random samples if unable to do it in the morning)
• Review if any interference with urine sample (contamination, menstruation, prior exercise, orthostatic proteinuria, or infections)
• Renal function assessed by eGFR
• Early stages are asymptomatic

• ACE inhibitors after confirming two urine samples > 30 mg/g (microalbuminuria)
• Refer to renal specialist if significant albuminuria (> 300 mg/g; macroalbuminuria) or hypertension to evaluate different aetiologies

• Maintain normal renal function, urine albumin to creatinine ratio, and blood pressure

• Optimise diabetes and weight management and treatment of dyslipidaemia/hypertension, if present
• Consider other causes of nephropathy

Peripheral neuropathy

• Foot examination, ankle reflexes, vibration sensation testing using 128 Hz tuning fork, pin prick sensation, and 10 g monofilament pressure (distal plantar aspect of great toes and metatarsal joints)

• Foot care education
• Refer to neurologist for further evaluation if abnormal neurological signs

• Individualised according to symptoms and signs

• Optimise diabetes and weight management and treatment of dyslipidaemia/hypertension, if present

Overweight and obesity

• Family history of obesity and other modifiable risk factors including environment
• Plot BMI according to age and gender (overweight, BMI 85th–95th percentile; obesity, BMI > 95th percentile)*
• Identify other comorbidities related to obesity*

• Healthy lifestyle and family involvement
• Reinforce adherence to metformin
• If taking insulin, optimise management to avoid further weight gain
• Treat other obesity comorbidities

• Small changes in BMI can improve comorbidities and are easier to achieve
• BMI closer to healthy range is ideal, as weight has impact on other comorbidities

• Possible use of newer treatments for type 2 diabetes that improve weight
• Bariatric surgery in selected cases with special considerations

Psychosocial: depression, high risk behaviour, eating disorders

• Quick screening tools for depression and/or referral for formal evaluation, if suspected, using PHQ‐2 or HEEADDSS assessment for adolescents
• Evaluation in every visit according to general impression on review*

• Early referral to mental health professionals
• School counselling
• Discuss involvement with peer support groups

• Should be individualised but aiming to improve general emotional wellbeing and social functioning (school/family)

• Presence of psychosocial disorders affects medication taking and increases overall morbidity

Reproductive health Menstrual cycle irregularities (PCOS)

• Menstrual cycle regularity*
• Presence of hyperandrogenism (hirsutism using the Ferriman–Gallwey scale and/or moderate to severe acne, and/or androgenic alopecia)
• Testosterone levels, Free Androgen Index, and sex hormone binding globulin if menstrual irregularities are present

• Treat according to symptoms and recent international evidence‐based guidelines for PCOS
• Combined oral contraceptive if irregular menstrual cycles and/or hirsutism
• Cosmetic therapies for treating hirsutism

• Individualised according to main complaining symptoms

• Discuss/educate about contraception, especially if sexually active and HbA_1c level is above target due to the high risks of hyperglycaemia in unplanned pregnancies
• Contraception is also required if taking teratogenic medications (ACE inhibitors, statins, newer oral/injectable agents
• Weight management

Liver disease

• Assess liver enzymes (aspartate aminotransferase and alanine aminotransferase)

• Refer to gastroenterologist if liver enzymes persist over three times the upper limit of the reference interval after 6 months despite weight loss and improved glycaemic control with treatment, or if there is further deterioration in liver enzymes

• Individualised according to liver enzymes results

• Optimise diabetes and weight management

Obstructive sleep apnoea

• Evaluate symptoms of obstructive sleep apnoea (snoring, morning sleepiness and stop breathing episodes)*

• Refer to a pulmonary physician for oximetry and/or sleep study

• Individualised according to sleep study results

• Weight management
• Sleep apnoea is associated with dyslipidaemia, hypertension and insulin resistance

Hypertension

• BP using appropriate cuff*
• Plot BP in percentiles charts for age, gender and height*
  • pre‐hypertension: BP, > 90th to < 95th or 120/80–129/80 mmHg
  • hypertension: BP ≥ 95th or 130/80 mmHg
• Ambulatory 24‐hour BP monitors can be useful if available

• Healthy lifestyle and family involvement if BP > 90 to < 95th or 120/80–129/80 mmHg
• ACE inhibitors if BP ≥ 95th or 130/80 mmHg after 6 months of improved lifestyle, and start at lower dose ARB as alternative if not tolerating ACE

• BP < 90th percentile for age and gender

• Weight management
• Renal referral if other pathology is suspected and/or treatment goals are hard to achieve
• Review other risk factors for cardiovascular disease and manage accordingly

Dyslipidaemia: high LDL cholesterol, low HDL cholesterol, high triglycerides

• Family history of dyslipidaemia
• Lipid profile (LDL, > 3.36 mmol/L; HDL, < 0.9 mmol/L; and triglycerides, > 1.7 mmol/L) ideally fasting and when lower HbA_1c level is achieved

• Healthy lifestyle and family involvement
• Reduce total dietary fat < 35% and saturated fat < 7% of total energy intake
• No trans fat intake
• Statins if high LDL cholesterol in spite of improved lifestyle for 6 months
• Fish oil/fibrates if high triglycerides

• LDL cholesterol < 2.6 mmol/L
• HDL cholesterol > 0.9 mmol/L
• Triglycerides < 1.7 mmol/L

• Weight management
• Review other risk factors for cardiovascular disease and manage accordingly