Professor Timothy Barrett explains that, although rare, type 2 diabetes in children is potentially life threatening and requires very prompt referral to secondary care
  • Childhood type 2 diabetes is rare, and often associated with obesity and ethnic minority populations, or with a family history of type 2 diabetes or cardiovascular disease
  • Children with diabetes need an accurate diagnosis and will die if left untreated. Any child or young person (up to 17 completed years) diagnosed with diabetes mellitus needs a same-day referral to secondary paediatric care
  • The cornerstone of management is lifestyle advice—this works best if it involves the whole family
  • Metformin and insulin are currently the only medicines licensed for use in children
  • Children with type 2 diabetes usually have coexisting morbidities; it is important to screen for hypertension, microalbuminuria, retinopathy, and dyslipidaemia.

In paediatric practice, type 1 diabetes accounts for about 96% of all affected children (approximately 25,000 individuals)1 and is characterised by an absolute insulin deficiency as a result of autoimmune destruction of insulin-producing beta cells in the pancreas. These children will die unless insulin therapy is instituted. By contrast, type 2 diabetes affects fewer than 500 children in the UK,1 and is characterised by insulin resistance secondary to obesity.2

Pathogenesis

Type 2 diabetes in children is frequently associated with other features of insulin resistance or metabolic syndrome, including obesity, dyslipidaemia, hypertension, albuminuria, ovarian hyperandrogenism, non-alcoholic fatty liver disease (NAFLD), and obstructive sleep apnoea.3 The natural history of type 2 diabetes in childhood starts with fasting hyperinsulinaemia, followed by postprandial hyperglycaemia. Owing to a combination of lipid and glucose toxicity on beta cells, which increases tissue insulin resistance and hepatic glucose output, fasting hyperglycaemia follows. In the liver, this impaired insulin-related inhibition of hepatic gluconeogenesis results in increased hepatic glucose output. In muscle, reduced transport of carbohydrates, combined with lipid deposition in muscle cells, leads to impaired exercise ability and increased tiredness with exercise. In fat tissue, there is impaired insulin-mediated inhibition of hormone-dependent lipase, with breakdown of lipids to free fatty acids and glycerol, contributing to the dyslipidaemia.

Current trends in the management of diabetes in children and young people

The management of children and young people with type 2 diabetes is a specialist area currently delivered in secondary care. This is because childhood diabetes is rare, with a prevalence rate of fewer than one affected child per average-sized practice.1

Moreover, many children require insulin treatment that needs adjusting with growth, and most will have additional complications of obesity that require specialist screening and treatment. NICE recommends that children and young people with diabetes should be offered an ongoing integrated package of care by a multidisciplinary paediatric diabetes care team.4 The important aspects for community services are correct diagnosis and awareness of complications when young people present with other acute or chronic problems.

Relevant guidance

NICE Clinical Guideline 15 on Type 1 diabetes: diagnosis and management of type 1 diabetes mellitus in children and young people4 (CG15: see publications.nice.org.uk/type-1-diabetes-cg15) is being revised and the updated document will include a section on management of type 2 diabetes in childhood (see www.nice.org.uk/guidance/CG/WaveR/118/Development). A useful review on type 2 diabetes and children and adolescents was published by The International Society for Paediatric and Adolescent Diabetes, and has informed this article.3

Signs and symptoms

Diabetes is diagnosed according to World Health Organization (WHO) criteria (see Box 1, above).5 Currently this requires a fasting, random capillary, or venous glucose estimation. However, recently revised American Diabetes Association (ADA) criteria have allowed the use of haemoglobin A1c (HbA1c) levels to be equal to or greater than 6.5% for diagnosis of diabetes. These criteria have been reviewed recently: a series of paediatric studies seem to show that HbA1c has lower sensitivity than a fasting plasma glucose or oral glucose tolerance test.6

The classic features of type 2 diabetes in childhood are listed in Box 2. Type 2 diabetes also disproportionately affects families of lower socio-economic status.

It is not unusual for children with type 2 diabetes to be identified coincidentally, even though they appear asymptomatic when screened either in primary care or on a glucose meter belonging to another family member with diabetes. However, a minority present with metabolic decompensation and diabetic ketoacidosis. A further group may present with severe hyperosmolar non-ketotic dehydration, which carries a high risk for fatality.7

It cannot be stressed strongly enough that if diabetes is suspected, then it is much safer to refer the same day to secondary care than to wait for metabolic decompensation, which could result in death from lack of treatment.

A capillary or laboratory plasma or venous glucose is necessary to make the diagnosis of diabetes mellitus. In addition to routine measurements of height, weight, and blood pressure, other investigations at the point of diagnosis should include an assessment of blood ketones. Hypertension is present in over 10% of children at diagnosis of diabetes, and the presence of diabetes doubles the risk for developing hypertension.8

Box 1: Diagnosis of diabetes according to the WHO criteria

  • Diabetes is diagnosed when:4
  • a fasting plasma glucose is equal to or greater than 7.0 mmol/L (126 mg/dL) OR
  • a random (post prandial) plasma glucose is equal to or greater than 11.1 mmol/L (200 mg/dL) OR
  • there are symptoms of thirst, polyuria, tiredness, and weight loss and a random plasma glucose equal to or greater than 11.1 mmol/L (200 mg/dL). This can be performed at any time of the day regardless of the time of the last meal
  • An oral glucose tolerance test should not be undertaken in primary care. This is a specialist investigation in childhood, which is potentially dangerous in an insulin dependent person with diabetes, and requires glucose load adjustment for body mass. Impaired fasting glycaemia and impaired glucose tolerance are intermediate stages in the pathogenesis of disordered carbohydrate metabolism, but are not diabetes mellitus.2

Box 2: Common presenting features of type 2 diabetes in children2

  • Aged 11–16 years—mean age of diagnosis is around 13 years
  • Overweight (South Asian UK children) or overweight or obese (S Asian, White UK, African-Caribbean children)
  • Ethnic minority origin, particularly as described above, but also Arabic, mixed race, or Chinese
  • Family history of type 2 diabetes or cardiovascular disease in siblings, parents, or more than one grandparent—found in approximately 85% of children with type 2 diabetes2
  • Presentation with pigmented thickening of the skin in the neck, axillae, or groin (acanthosis nigricans)
  • Superficial skin or soft tissue infections
  • Symptoms of thirst, polyuria, or thrush.

Management approaches

The main emphasis in the management of type 2 diabetes is on lifestyle modification. The overall management goals are to achieve weight loss and an increase in exercise capacity.3 The risk of microvascular and macrovascular complications increases in children, young people and adults with both the duration of diabetes and lack of glycaemic control,9 so it is vital that metabolic control is achieved and sustained through:

  • normalisation of glycaemia
  • control of co-morbidities including hypertension, dyslipidaemia, nephropathy, and NAFLD.3

Education around lifestyle modification involves not just the child but also his/her family. The whole family may need education to understand the principles of treatment for type 2 diabetes and the critical importance of lifestyle changes if chronic complications are to be prevented.3 The family should be encouraged to change its diet consistent with healthy eating recommendations, including individualised counselling for weight reduction, reduced total and saturated fat intake, and increased fibre intake. The key areas that have been found to be important in children include:

  • the elimination of sugar-containing soft drinks and juice
  • taking meals on schedule, in one place in the absence of other activities (e.g. TV), and ideally as a family group
  • portion control by reducing portion sizes
  • limiting high-fat, high-calorie food in the home.3

Exercise management means developing individual exercise programmes that are enjoyable, affordable for the family, and participated in by at least one other family member. Families should be encouraged to develop an achievable daily exercise programme, including reduced sedentary time. Opportunities may include:3

  • using stairs instead of elevators
  • walking part of the way to school
  • using an exercise machine or exercise DVDs at home
  • walking with a family member after school.

The UK guideline10 recommendation of at least 1 hour a day of exercise that makes one out of breath is not usually achievable for children with type 2 diabetes, at least initially. Any exercise is beneficial, and promoting achievable targets with a gradual build up may avoid disillusionment.

Pharmacological interventions

First-line pharmacological therapy should always be metformin as there is a reasonable evidence base for its use and a good safety profile, without risk of hypoglycaemia. It is standard UK practice to start therapy with metformin from diagnosis, alongside diet, exercise, and lifestyle modification.3 Metformin:

  • belongs to a class of drugs called biguanides
  • acts on insulin receptors in fat, muscle, and the liver
  • reduces hepatic glucose production by decreasing gluconeogenesis
  • increases insulin-stimulated glucose uptake
  • may have some effect on reducing appetite
  • can reduce HbA1c by 1–2%.11

A recent large, randomised, controlled trial comparing three treatment regimens found that monotherapy with metformin alone was associated with durable glycaemic control in about one-half of children and adolescents with type 2 diabetes.12 It can, however, have intestinal side-effects including transient abdominal pain, diarrhoea, and nausea. The usual starting dose is 500 mg once a day, increasing over 3–4 weeks to the maximum tolerated dose, or 2 g/day, in two divided doses.3 However, there is a liquid preparation available (250 mg/5 ml) which will allow a slower titration of dose; or alternatively, an extended-release preparation. There is also the advantage that for girls with the complication of polycystic ovarian syndrome, metformin may normalise ovulatory abnormalities. This may of course increase the risk of pregnancy and girls need to be counselled about this.13

The use of insulin in children with type 2 diabetes is a specialist area and treatment should be managed in secondary care.

All other pharmacological agents are not currently approved for use in children and young people under 18 years of age. Bariatric surgery may in future be considered for adolescents with obesity- related complications, including type 2 diabetes.3

Monitoring of blood glucose

Self-monitoring of capillary blood glucose is very important in childhood diabetes to detect hyperglycaemia and its response to interventions. This should be undertaken regularly and include a combination of fasting and postprandial (taken approximately 1.5 hours after meals) glucose checks. Once glycaemic goals have been met the frequency of monitoring (based on the author’s experience) may be reduced to 2–3 fasting and 2–3 postprandial capillary checks per week. Testing should be undertaken more frequently during intercurrent illness. Clearly, children on insulin therapy should be undertaking more frequent testing. Glycated haemoglobin should be assessed every 3 months if the individual is receiving insulin treatment.4

When to refer for specialist advice

All children in whom a diagnosis of diabetes mellitus is made should be referred to secondary care the same day. Children and young people with either type 1 and type 2 diabetes can decompensate much faster than adults and progress to diabetic ketoacidosis with reduced consciousness in hours, not days. It is essential that a same-day referral is made by telephone to a secondary care paediatric unit. Children need urgent assessment for circulation status, ketoacidosis, and insulin requirement.4

Prevention of type 2 diabetes in children

The UK has not seen the rapid rise of childhood type 2 diabetes expected 10 years ago. However, the large numbers of children with obesity and impaired glucose tolerance suggest that there is still potential for increasing numbers of children to develop type 2 diabetes. Prevention of childhood-onset type 2 diabetes requires prevention of obesity, particularly in at-risk groups such as children from ethnic minorities. Primary prevention of type 2 diabetes involves the reversal of eating and entertainment trends in homes, schools, and communities that lead to excess calorie intake and decreased energy expenditure. This is an issue for the whole of society; as healthcare professionals, our role is to promote healthy lifestyle messages in all our interactions with the general public.

Commissioning

For the purposes of the current NHS England Best Practice Tariff, children with type 2 diabetes are treated as if they had type 1 diabetes.14 Currently, care for children with type 2 diabetes is commissioned in the same way as for children with type 1 diabetes.

Conclusion

It is important to raise awareness that:

  • type 2 diabetes does occur in childhood
  • type 2 diabetes is potentially as serious as type 1 diabetes in children
  • children with type 2 diabetes can undergo rapid metabolic decompensation.

The key priority is to make the diagnosis of diabetes correctly and then to ensure a same-day referral to secondary paediatric care. The ongoing priority is to promote healthy lifestyle choices to children and their families.

  • Type 2 diabetes is such a rare condition in children that each CCG is likely to be responsible for commissioning services for fewer than five patients
  • CCGs, particularly those with high populations of non-Europeans, might consider prevention and awareness programmes for obesity and type 2 diabetes in children
  • Such programmes would be best coordinated through Health and Wellbeing Boards, with links to education services
  • Simple awareness programmes on the recognition of diabetes in children for primary care clinicians could include reference to type 2 diabetes and emphasise the need for same-day referral to specialist services when diabetes is suspected
  • The best-practice tariff for paediatric diabetes does cover type 2 diabetes and is payable when strict criteria for a specialist service are met—CCGs should agree these with local trusts
  • Tariff costs = £2764 for 1 year of outpatient care.a

CCG=clinical commissioning group
www.gov.uk/government/publications/payment-by-results-pbr-operational-guidance-and-tariffs

  1. Royal College of Paediatrics and Child Health. Growing up with diabetes: children and young people with diabetes in England. RCPCH publications, March 2009. Available at:
    www.rcpch.ac.uk/system/files/protected/news/FINAL_CYP_Diabetes_Survey_Report_(3)[1].pdf.
  2. Haines L, Wan K, Lynn R et al. Rising incidence of type 2 diabetes in children in the United Kingdom. Diabetes Care 2007; 30: 1097–1100.
  3. Rosenbloom A, Silverstein J, Amemiya S et al. Type 2 diabetes in children and adolescents. Pediatric Diabetes 2009; 10 (Suppl 12): 17–32.
  4. NICE. Type 1 diabetes: diagnosis and management of type 1 diabetes in children, young people and adults. Clinical Guideline 15. London: NICE, 2004. Available at: www.nice.org.uk/cg15
  5. World Health Organization, International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Geneva: WHO, 2006. Available at: www.diabetes.org.uk/Documents/Professionals/Definition_and_diagnosis1111.pdf
  6. Kapadia C. Are the ADA hemoglobin A(1c) criteria relevant for the diagnosis of type 2 diabetes in youth? Curr Diab Rep 2013; 13 (1): 51–55.
  7. Morales A, Rosenbloom A. Death caused by hyperglycaemic hyperosmolar state at the onset of type 2 diabetes. J Pediatr 2004; 144: 270–273.
  8. Eppens M, Craig M, Jones T et al on behalf of The International Diabetes Federation Western Pacific Region Steering Committee. Type 2 diabetes in youth from the Western Pacific Region: glycaemic control, diabetes care and complications. Curr Med Res Opinion 2006; 22: 1013–1020.
  9. [No authors listed]. Intensive glucose control with sulphonylureas of insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) group. Lancet 1998; 352 (9131): 837–853.
  10. Department of Health. Physical activity guidelines for children and young people (5–18 years). Fact sheet 3, 2011. Available at: www.gov.uk/government/uploads/system/uploads/attachment_data/file/135115/dh_128144.pdf
  11. TODAY study group. A clinical trial to maintain glycaemic control in youth with type 2 diabetes. N Eng J Med 2012; 366 (24): 2247–2256. Available at: www.nejm.org/doi/full/10.1056/NEJMoa1109333
  12. Jones K, Arslanian S, Peterokova V et al. Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Diabetes Care 2002; 25 (1): 89–94.
  13. Heard M, Pierce A, Carson S, Buster J. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril 2002; 77 (4): 669–673.
  14. Randell T. Paediatric diabetes best practice tariff criteria. NHS Diabetes, 2012. Available at: www.diabetes.nhs.uk/networks/paediatric_network/best_practice_tariff_for_paediatric_diabetes/# G