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Type 2 diabetes in younger adults: the emerging UK epidemic
  1. Emma G Wilmot1,2,
  2. Melanie J Davies1,2,
  3. Tom Yates1,2,
  4. Katrien Benhalima1,
  5. Ian G Lawrence1,
  6. Kamlesh Khunti3
  1. 1Diabetes Research Department, University Hospitals of Leicester, UK
  2. 2Department of Cardiovascular Sciences, Leicester University, Leicester, UK
  3. 3Department of Health Sciences, Leicester University, Leicester UK
  1. Correspondence to Dr Emma G Wilmot, Diabetes Research Department, Level 1, Knighton St OPD, Leicester Royal Infirmary, Leicester LE1 5WW, UK; emma.wilmot{at}uhl-tr.nhs.uk

Abstract

There is an emerging epidemic of type 2 diabetes (T2DM) in younger adults. They represent an extreme phenotype: likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black or minority ethnic origin, and come from less affluent socioeconomic groups. An accurate diagnosis of T2DM in younger adults, while essential to guide management, can be challenging even for the experienced diabetologist. Comorbidities such as hypertension, nephropathy and hyperlipidaemia are prevalent in this group, and, despite the lack of longitudinal data, they represent a very high risk group, with a need for aggressive management. This focused review of the epidemiology, aetiology, clinical outcomes, comorbidities and management of younger adults with T2DM will provide the non-specialist with up-to-date insight into the UK's emerging epidemic.

  • Diabetes mellitus
  • type 2
  • diabetes mellitus
  • classification
  • type 2 diabetes
  • youth onset
  • type 2 diabetes
  • risk factors
  • diabetes & endocrinology
  • general diabetes
  • diabetes & endocrinology

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Introduction

Until recently type 2 diabetes (T2DM) was considered a disease of older adults, but we are now seeing the condition diagnosed in children, adolescents and young adults under the age of 30.1–4 While type 1 diabetes (T1DM) remains the main form of diabetes in young people, it is expected that T2DM will be the predominant form within 10 years in some ethnic groups.5

The onset of T2DM in younger adults presents a number of problems for both the individual and society. The youth with T2DM represents an extreme phenotype. They are likely to be obese, have a multigenerational family history of T2DM, lead a sedentary lifestyle, be of black or minority ethnic origin, and come from socially deprived groups.6–8 From a societal perspective, the increase in younger adults developing T2DM has substantial implications for future workforce and healthcare systems.

The main objectives of this review are to:

  • Describe the epidemiology of T2DM in younger adults, with particular reference to the UK

  • Describe the typical phenotype of the younger adult with T2DM: the clinical presentation and diagnostic difficulties

  • Outline the complications, comorbidities and management

  • Discuss the impact of T2DM on women of childbearing age

Definition of T2DM in younger adults

T2DM in younger adults has been defined in a variety of ways, often separating the paediatric (<18 years) from the adult (≥18 years) population. However, there is a continuum of risk associated with an earlier diagnosis of T2DM, and this distinction may fail to recognise the potential for poorer outcomes in patients diagnosed in their third and fourth decades of life. For the purpose of this review, T2DM in younger adults will include the high-risk cohort up to and including the age of 45 years. This cut-off has been selected for two reasons: firstly, there is a fourfold increase in the risk of myocardial infarction for those diagnosed with T2DM <45 years compared with those aged ≥45 years9; secondly, the cut-off of <45 years will include women of childbearing age, a cohort that requires special consideration.

Epidemiology

Most of the evidence for an epidemic of T2DM in younger people has come from paediatric data from Japan and the USA. Between 1990 and 2000, New York experienced a 10-fold increase in the prevalence of T2DM in children.10 The SEARCH for Diabetes in Youth Study in America has reported incidence and prevalence rates of 3.7–19/100 000 per year and 0.18–1.06/1000, respectively, with higher rates seen in black and minority ethnic groups.2 11–14 Japan has also experienced a doubling of the incidence of T2DM in children between the late 1980s and early 1990s, and T2DM is now the most likely diagnosis in a child presenting with diabetes in this country.1 T2DM in younger adults has also been reported in China, Mexico, India and Australia.3 15–17 However, reports in the Europe are rarer. A European survey and literature review in 2005 discovered only 184 children and adolescents with T2DM, of which the majority were Caucasian and female with a positive family history of T2DM.18 A more recent population-wide study in Germany identified 562 children with T2DM, representing 1.4% of the diabetic population under the age of 20 years.19

Most UK data on the incidence and prevalence of T2DM in younger adults have relied on reports from secondary-care paediatric units. A cross-sectional questionnaire survey of all UK paediatric centres in 2000 identified 25 patients under the age of 16 years with T2DM, with a crude prevalence of 0.21/100 000.20 A prospective monthly surveillance of UK paediatricians between 2004 and 2005 estimated the incidence of T2DM in those <17 years to be 0.6/100 000 per year, much lower than the SEARCH for Diabetes in Youth figures.7 21 However, UK surveys have relied on doctors and nurses reporting data to a central surveillance unit and are therefore likely to underestimate the true incidence of T2DM in this age group within the UK.

Some of the UK population data on the prevalence of T2DM in children and adolescents are derived from general practice prescriptions of oral antidiabetic therapies. This recently published retrospective cohort study analysed prescriptions issued between 1998 and 2005 for 505 754 young adults aged <18 years. During this period there was an eightfold increase in prescriptions for oral antidiabetic therapy.22 The prevalence of T2DM in this study was estimated at 1.9/100 000, almost 10 times higher than the original report in 2000 of 0.21/100 000. This is probably a refection of the limitations of the previous questionnaire-based surveys and the fact that the paediatric surveillance surveys gathered data on those up to the age of 16, whereas the general practice prescription database looked at children up to 18 years of age. Nonetheless, these data are striking, indicating a significant rise in the incidence and prevalence of T2DM in youth in the UK.

The most recent data on T2DM in younger adults are from a national survey of England in 2009. This identified 328 youth under the age of 18 with T2DM, representing 1.5% of the total diabetic population in this age group. The estimated prevalence was 3.0/100 000, with peak prevalence in 10–14 year olds.23 This report adds further support to the hypothesis that we are seeing a rapid rise in the prevalence of T2DM in younger people in the UK (table 1).

Table 1

UK studies examining the prevalence of type 2 diabetes (T2DM) in children and adolescents

Many publications have focused on the paediatric population specifically; however, there are some data available from adult diabetes services. A hospital-based cross-sectional study in Leeds in 2003 described a crude prevalence of 0.13/1000, representing 5% of their diabetes clinic population under the age of 30 years with T2DM.6 A further study in Sheffield in 2008 identified 527 people with T2DM diagnosed before the age of 40 years, representing 24% of their total clinic population.24 Data from a retrospective review of our secondary-care diabetes service in Leicestershire identified 185 people with T2DM under the age of 35 years, representing 14% of the diabetes clinic population.25 These data suggest that T2DM diagnosed in younger adults represents a substantial proportion of patients utilising secondary-care services.

Although there is increasing evidence for a rise in the incidence and prevalence of T2DM in younger adults in the UK, more robust epidemiological data are required to describe this population and the associated natural history and clinical outcomes.

Risk factors

The risk factors for T2DM in youth are similar to those for late-onset T2DM, with the additional risk factors of puberty contributing to insulin resistance. Also, in contrast with late-onset T2DM diabetes, T2DM in youth is more common in females (table 2).

Table 2

Risk factors for type 2 diabetes (T2DM) in youth

Obesity

Obesity is one of the main factors driving increasing rates of T2DM in younger people. Obesity is the outcome of a positive energy balance, often the result of the combination of excess dietary intake and a sedentary lifestyle. A large proportion (80–92%) of young adults diagnosed with T2DM in the UK are obese20 21 compared with only 56% of adults.26 These data are in keeping with international findings.27 Data from America28 demonstrate an inverse linear relationship between body mass index (BMI) and the age at diagnosis of T2DM. An age at diagnosis of <30, 51–55 and >70 years was associated with a BMI of 38.3, 35.0 and 28.8 kg/m2, respectively.28 These data support the hypothesis that T2DM in younger adults is driven by increasing levels of obesity.

Low physical activity

Physical inactivity is a key factor in the obesity and diabetes epidemic in younger people. The European Youth Heart Study found that clustered metabolic risk (including insulin sensitivity) increased in a dose–response manner with decreasing physical activity in children aged 9–15 years.29 30 Longitudinal data from the USA have clearly demonstrated that the steep decline in physical activity in adolescence is associated with increased weight gain.31 This is concerning given that recent accelerometer data from the UK have highlighted that only 7% of boys and 0% of girls aged 11–15 years met the government recommendations of 60 min of physical activity per day.32

Family history

Family history of diabetes and genetic predisposition undoubtedly play a significant role in the development of T2DM in youth. In the UK, 84% of adolescents with T2DM have a family history of T2DM, and 56–71% have a parent or sibling affected.7 21 Both genetic and environmental factors will have a role to play. Although there is clear evidence of a genetic predisposition to insulin resistance, families often share a similar environment.33

Ethnicity

Internationally, Japanese, Hispanics and Native Americans have the highest risks of developing T2DM in childhood.2 13 14 34 In the UK, 43–56% are from a black or minority ethnic origin, with prevalence rates of 3.9/100 000 in black children and 1.25/100 000 in South Asians compared with the much lower rate of 0.35/100 000 in white children.7

Clinical presentation and diagnostic criteria

The younger person with T2DM is often obese, from a black or minority ethnic background, and has a family history of diabetes. However, with increasing rates of obesity in the general UK population, making a diagnosis of T2DM is not as straightforward as it might first appear. Getting the diagnosis correct is crucial—misdiagnosing a patient with T2DM when they actually have T1DM could be life-threatening if the choice of management is metformin and not insulin, a life-saving treatment in T1DM. Labelling a patient with T1DM when they actually have T2DM could be similarly disastrous, as the patient may be subjected to life-long unnecessary treatment with insulin instead of being given the option of oral therapies, or some of the newer weight loss inducing incretin mimetic treatments. Misclassification may also result in negative psychological effects in both the individual and their family.35 Even if the misclassification is corrected, such effects may persist—for example, annoyance and a lack of confidence in the doctor for both inappropriate labelling and the resultant suboptimal management.36

It is therefore essential that patients are correctly classified at diagnosis. T2DM occurs when insulin secretion is inadequate to meet the increased demand posed by insulin resistance and therefore other features of insulin resistance are often present in patients with T2DM: hypertension, hyperlipidaemia, acanthosis nigricans (a cutaneous manifestation of insulin resistance), polycystic ovarian syndrome and non-alcoholic fatty liver disease (NAFLD).

In addition to the clinical features, the clinical presentation can help to guide the physician. T1DM often has a rapid onset with a few weeks history of polyuria, polydipsia and weight loss, and, at presentation, most of these patients have decompensation in the form of ketosis or diabetic ketoacidosis. In contrast, the patient with T2DM presents insidiously—many are diagnosed as an incidental finding or some may present with osmotic symptoms. However, confusion can arise because up to a third of patients with T2DM can present with ketosis or ketoacidosis, which can result in misclassification as T1DM.37

Ketosis-prone T2DM describes a group of patients who present with ketosis or ketoacidosis and then enter a period of near normoglycaemia remission. Ketosis-prone T2DM can affect up to 50% of African–American and Hispanic patients presenting with diabetic ketoacidosis.38 39 These patients have the typical phenotype of T2DM in youth: usually obese, with a strong family history of diabetes. At diagnosis they have severe impairment of their insulin secretion. This improves with insulin therapy, often allowing the discontinuation of insulin after a few months of treatment. This unexplained effect is thought to result from the ‘glucotoxic’ effects of hyperglycaemia on the β cells in the pancreas.40 41 When in remission, these patients can be managed on low-dose sulfonylurea or metformin; diet alone has been shown to shorten the remission period.41 42

Monogenic diabetes, formerly known as maturity-onset diabetes in the young (MODY), is a diagnosis that should be considered in younger patients presenting with atypical diabetes. At the turn of the century, monogenic diabetes was more common than T2DM in children, although more recent European reports would suggest that this is no longer the case.19 20 Monogenic diabetes is an inherited condition arising from a mutation in a single gene that regulates β cell function. Previous classification of MODY included a diagnosis of diabetes <25 years, autosomal dominant inheritance, and non-insulin dependence.20 43 However, many younger patients with T2DM also meet these criteria, and therefore the classification has subsequently been revised.44 A diagnosis of monogenic diabetes should be considered when the patient is not markedly obese, is from an ethnic background with a low prevalence of T2DM (eg, Caucasian), and has no evidence of insulin resistance (a fasting C-peptide in the normal range and no acanthosis nigricans).44 If suspected, monogenic diabetes should be confirmed with molecular genetic testing, especially in cases where a diagnosis of monogenic diabetes could alter the clinical management (for instance, in the case of hepatocyte nuclear factor-1 alpha (HNF1α), patients are sulfonylurea-sensitive allowing discontinuation of insulin therapy). Further information can be obtained from the ISPAD clinical consensus guidelines.44

A further consideration in making a diagnosis of T2DM in a young person is the role of autoantibodies such as glutamic acid decarboxylase, islet cell or insulin autoantibody. Previous studies have used the presence or absence of autoantibodies to classify patients with T1DM or T2DM, respectively.7 However, the recent International Society for Paediatric and Adolescent Diabetes clinical practice consensus guidelines have identified ‘autoimmune T2DM’ as a classification in light of the fact that 15–40% of youth and adults with T2DM have T1DM-associated antibodies, including those not requiring insulin 1 year after diagnosis.45 However, these patients have significantly impaired insulin secretion and many require insulin treatment at an earlier stage, raising the possibility that they represent autoimmune T1DM with obesity-induced insulin resistance.46 Therefore autoantibodies cannot be viewed as a diagnostic tool, but may guide clinical management. For that reason, current guidelines recommend that these are measured at the time of diagnosis in all young people presenting with diabetes.45

Laboratory measures that further aid the classification of diabetes subtype include insulin and C-peptide concentrations. A high serum C-peptide concentration is indicative of endogenous insulin secretion, and a persistently raised value would be unusual in T1DM.45 However, there is substantial overlap in insulin and C-peptide concentrations between T1DM and T2DM at diagnosis, so these laboratory tests are often not useful until the patient has had diabetes for several years. The recent development of a post-meal urine C-peptide/creatinine ratio may allow an inexpensive and practical differentiation between diabetes subtypes. Preliminary data have suggested that this non-invasive, home-based test can reliably distinguish between T1DM and T2DM.47

Determining the diagnosis of a young person with T2DM can be difficult. There is no clear-cut definition, and the diagnosis is often a balance of probability and minimisation of risk to the patient. It can often take months or years to ascertain diabetes classification, and a label of ‘Diabetes—cause uncertain’ is entirely appropriate during this time.48 If there is any doubt over the classification at diagnosis and the patient is symptomatic, it is safest to treat with insulin to prevent decompensation. Given the complexity associated with such cases, we would advocate specialist input and management, at least initially, of any young person presenting with new-onset diabetes. Table 3 lists some of the main distinguishing features of T1DM, T2DM and monogenic diabetes.

Table 3

Features that help differentiate between type 1 diabetes, type 2 diabetes and monogenic diabetes in children and adolescents presenting with diabetes

Clinical outcomes

Microvascular complications

Nephropathy

A high proportion of children and adolescents with T2DM have microalbuminuria, with prevalence estimates of 7–22% at diagnosis, 28–42% 5 years after diagnosis, and 60% 10 years after diagnosis.50 Younger adults with T2DM aged <18 years have higher rates of microalbuminuria (28 vs 6%) and hypertension (36 vs 16%) compared with people with T1DM, despite a shorter duration of diabetes (1.3 years vs 6.8 years) and lower HbA1c (7.3% vs 8.5%).50

Neuropathy

Comparing a sample of UK adolescents with T2DM (n=7) and T1DM (n=120), 57% of those with T2DM had evidence of peripheral neuropathy when assessed using light touch/vibration sense, whereas none of those with T1DM had evidence of peripheral neuropathy.51 In another UK study, 12 of 30 (40%) patients aged 13–35 years had evidence of neuropathy, six (20%) of whom had evidence of ulceration.52 This would suggest that neuropathy can present in younger adults with T2DM at an earlier stage (mean duration of diabetes was 1.8 years).

Retinopathy

Limited data are available on retinopathy in younger adults with T2DM, especially from the UK. Overall, studies suggest that retinopathy is rare in T2DM compared with T1DM in younger adults, although these figures fail to account for the dramatically shorter duration of diabetes in T2DM.21 50 A population-based cohort study in Sweden found similar rates of retinopathy between groups, but the incidence of severe retinopathy was significantly higher in younger adults aged 15–34 years with T2DM than in those with T1DM, both at diagnosis and follow-up 10 years on.53 In a survey of UK children with T2DM, no retinopathy was reported, but this is likely to be an underestimate given that 22% of this population were not screened.21

Macrovascular complications

Cardiovascular risk factors

Lipids

Dyslipidaemia is very common, with raised cholesterol and triglyceride concentrations in 33–60% of younger adults aged <18 years with T2DM.11 50 54 55 These rates are higher than rates found in non-diabetic obese counterparts, suggesting that the diagnosis of diabetes has an additive impact on dyslipidaemia.

Hypertension

Around half (30–55%) of adolescents with T2DM are hypertensive at presentation.50 54 55 From UK paediatric data, only one in five patients aged <17 years had a recorded blood pressure measurement; 34% were hypertensive, although none were receiving treatment.21

Surrogate markers of cardiovascular disease

T2DM in younger adults is still a relatively recent phenomenon, and, given the paucity of data on cardiovascular outcomes, we are currently reliant on surrogate markers of heightened cardiovascular risk. Aortic pulse wave velocity, a predictor of cardiovascular mortality in adults, is significantly higher in adolescents with T2DM than in age-matched obese and T1DM controls.56 57 Vascular stiffness was comparable to that in adults aged >40 years.56 Young adults with T2DM have also been found to have abnormalities in carotid structure, with significantly greater carotid intima-media thickness than lean and obese age matched controls.58 These data provide support for the assumption that T2DM in younger adults will be associated with poor cardiovascular outcomes in the future.

Cardiovascular morbidity and mortality

There are only limited follow-up data on T2DM in younger adults, and, to date, we are unable to adequately describe cardiovascular outcomes in this rapidly expanding group. Preliminary data from 69 First Nation Canadian adolescents with T2DM, followed-up for 9 years, showed that the mortality during this period was 9%. Of the remaining survivors, 35% developed microalbuminuria, 45% were hypertensive, and 6% were on dialysis.59 However, these patients were cared for in a pre-United Kingdom Prospective Diabetes Study (UKPDS)/pre-Diabetes Control and Complications Trial (DCCT) era, and their glycaemic control was extremely poor, with a mean HbA1c of 10.9%.

There is further evidence available from America that supports the hypothesis that outcomes in young-onset T2DM will be worse than in late onset. For instance, the hazard of developing a myocardial infarct in early-onset T2DM (<45 years) is fourfold higher than in late-onset T2DM (≥45 years) and 14-fold higher than in people without diabetes.9 This evidence for increased cardiovascular morbidity in those diagnosed with T2DM at a younger age is further supported by a large prospective cohort study of 4857 American–Indian children who were followed-up for 24 years. In this study, obesity, glucose intolerance and hypertension increased the risk of premature death by 130%, 73% and 57%, respectively.60 Although these studies did not examine the impact of T2DM per se, they provide some insight into the potentially devastating impact of T2DM in younger adults in the future.

Non-alcoholic fatty liver disease

NAFLD is the most common liver abnormality seen in children61 and is present in ∼50% of children with T2DM.62 There is a spectrum of NAFLD ranging from infiltration (steatosis) to inflammation (steatohepatitis) to liver cirrhosis. It is commonly associated with insulin resistance. A ‘multi-hit’ hypothesis has been proposed to describe the pathogenesis of NAFLD.63 64 Insulin resistance and the associated increase in free fatty acids that are absorbed by the liver represent the first ‘hit’ and the development of steatosis. The second ‘hit’ involves the complex interactions between hepatocytes, adipose cells and inflammatory biomarkers, which result in inflammation or cirrhosis.64

Affected individuals are often asymptomatic, and the most common manifestation of this condition is raised alanine aminotransferase, typically higher than aspartate aminotransferase. Of those with NAFLD, 30% will have fatigue, 30% will have right upper quadrant abdominal pain, and 25% will have enlargement of the liver on ultrasound.62 Many children with NAFLD will go on to develop liver fibrosis or cirrhosis, with 3–10% already having cirrhosis at the time of liver biopsy. A 20 year follow-up study of adolescents with NAFLD (without diabetes) reported that 6% died or required a liver transplant, with a standardised mortality ratio of 13.6.65 This would suggest that the combination of T2DM and NAFLD developing early in life is likely to lead to substantial morbidity and mortality.

There is an urgent need for effective therapies to prevent progression to liver fibrosis. The insulin-sensitising glitazones improve steatosis and inflammation in NAFLD, raising the question of whether these agents should be prioritised for use in patients with T2DM with NAFLD.66 67 However, there is no robust evidence for a reduction in liver fibrosis, and side effects include persistent weight gain, oedema and an increased fracture risk.68–70 Although the effect on histology is unclear, diet, exercise and metformin have all been associated with improvements in liver function tests and inflammation, and therefore we would advocate these treatments as first-line therapies in younger adults with T2DM and NAFLD.71–74

T2DM and pregnancy

There has been a substantial increase in the number of women with T2DM attending maternity services. A third of the women in the UK Confidential Enquiry into Maternal and Child Health (CEMACH) report had T2DM.75 T2DM in pregnancy is associated with a number of risks for both the mother and fetus, with outcomes just as poor as for women with T1DM. These include miscarriage, preterm labour, macrosomia, birth injury, neonatal hypoglycaemia and stillbirth in addition to a twofold increase in the rate of congenital malformations and a threefold increase in the risk of perinatal mortality.75

The risks associated with diabetes and pregnancy can be minimised through meticulous glycaemic control (HbA1c <6.1%), high-dose folic acid (5 mg a day) combined with close monitoring of the mother and fetus.76 Unfortunately women with T2DM are less likely to have prepregnancy counselling, preconception folic acid, or a test of glycaemic control in the 6 months before conception compared with women with T1DM.75

As highlighted in the complications section, young women with T2DM often have other comorbidities (eg, obesity, hypertension, microalbuminuria) in addition to diabetes, which further increase the risks in pregnancy. Despite the equal prevalence of comorbidities in males and females, there seems to be a reluctance to treat women of childbearing age as aggressively as men. An audit of our local population with T2DM <35 years revealed that fewer women were treated for hypertension (22% vs 43%, p<0.01) and hypercholesterolaemia (16% vs 43%, p<0.01) than men, despite similar rates of hypercholesterolaemia and hypertension.77

Nonetheless, UK data from our group show a rapid increase in the use of teratogenic antihypertensive and statin therapies in young women with T2DM over the past 10 years, with no concomitant increase in the use of contraception.78 This is a reflection of the fact that only one in 10 women has a documented discussion about the risks of diabetes and pregnancy, and only four in 10 are given advice on contraception.75 The use of teratogenic agents in women who may become pregnant should be actively avoided.

Management

Currently, metformin and insulin are the only drugs approved for use in the paediatric population with T2DM. Metformin inhibits gluconeogenesis and promotes peripheral glucose uptake, improving glucose sensitivity. Two trials have assessed traditional oral hypoglycaemic agents in young people with T2DM. In 2002, a mutlicentre double-blind trial concluded that metformin was safe to use in 82 subjects aged 10–16 years for up to 16 weeks. This period was associated with a reduction in HbA1c of 1.2% and a 3.6 mmol/l reduction in fasting glucose compared with the placebo arm.79 Glimepiride, a sulfonylurea, promotes insulin secretion. In 2007, a single blind multinational study reported that glimepiride reduced HbA1c similarly to metformin in 263 young people with T2DM (mean age 13.8 years). However, the use of glimepiride was associated with a 1.97 kg weight gain, compared with only 0.55 kg in the metformin group. Safety profiles of both drugs were comparable over the 26-week follow-up period.80

Older adolescents and those over 20 years have access to the full range of antidiabetic therapeutic options including gliptins and glucagon-like peptide (GLP)-1 analogues. GLP-1 is released upon ingestion of food, resulting in improved insulin secretion, delayed gastric emptying, and the promotion of satiety. Recent advances in the management of T2DM in adults include GLP-1 analogues such as exenatide and liraglutide. The main advantage of these agents over other existing therapies is the combination of improvement in glycaemic control with significant weight loss, the elusive goal in T2DM therapy.81 Such agents would, in theory, benefit the younger T2DM population, who tend to have a higher BMI at diagnosis than older adults, but, to date, clinical trials to assess outcomes in this younger target population have not been performed.

In terms of cardiovascular risk management, lifestyle interventions to reduce weight and increase physical activity are advocated. If, following such changes, younger adults with T2DM have persistent hyperlipidaemia or hypertension, a statin or ACE inhibitor should be initiated.45 However, to date there have been no pharmacotherapeutic outcome studies of management of hypertension or dyslipidaemia in younger adults with T2DM.

Conclusion

There is an urgent need to develop a full understanding of the natural history of T2DM in younger adults, which includes determining population-based prevalence rates and the natural history of comorbidities and complications. As demonstrated, these data are particularly lacking in Europe. The true extent of the morbidity and mortality associated with T2DM in younger adults will not be fully realised for another 10–20 years in Westernised society. It is therefore imperative that effective primary and secondary prevention strategies are rapidly developed to lessen the growing burden of T2DM on the individual, society, healthcare systems and work forces throughout the developed world.

Multiple-choice questions (true (T)/false (F); answers after the references)

1. Reasons for the increasing incidence and prevalence of type 2 diabetes (T2DM) in younger people include:

  1. Physical inactivity

  2. Obesity

  3. Alcohol excess

  4. Genetic factors

  5. Diet

2. When making a diagnosis of T2DM in a younger adult:

  1. If asymptomatic, two oral glucose tolerance tests in the diabetic range will be required to make a diagnosis of diabetes

  2. Insulin and C-peptide values differentiate between T1DM and T2DM

  3. The result of glutamic acid decarboxlyase antibodies distinguish T1DM from T2DM

  4. A family history of diabetes supports a diagnosis of T1DM versus T2DM

  5. Acanthosis nigricans is a marker of hyperinsulinaemia

3. An obese adolescent aged 16 years presents with thirst and polyuria. The random glucose is 17 mmol/l:

  1. This patient has a confirmed diagnosis of diabetes

  2. T1DM is the most likely diagnosis

  3. Ketones in the urine exclude a diagnosis of T2DM

  4. Acanthosis nigricans and a low high-density lipoprotein concentration would be supportive of a diagnosis of T2DM

  5. A diagnosis of maturity-onset diabetes in the young should be considered if the patient has a family history of diabetes affecting his mother, maternal aunt and maternal grandmother

4. An obese adolescent with T2DM has abnormal liver function with an alanine aminotransferase activity twice the upper limit of normal. Secondary causes of liver disease have been excluded and the liver ultrasound confirms the appearance of a fatty liver:

  1. Lifestyle modification (diet and exercise) may improve liver function tests

  2. Statin therapy is contraindicated in this patient

  3. This patient may experience pain from their fatty liver

  4. Fatty liver represents an additional cardiovascular risk factor in this patient

  5. There is a future risk of progression to liver cirrhosis

5. T2DM in the young is associated with:

  1. Acanthosis nigricans

  2. Polycystic ovarian syndrome

  3. Metabolic syndrome

  4. Rheumatoid arthritis

  5. Non-alcoholic fatty liver disease

Main messages

  • T2DM in young people in the UK is increasingly common; there was an eightfold increase in T2DM in young adults between 1998 and 2005.

  • The main risk factors for T2DM in younger people are obesity, physical inactivity, ethnicity and a family history of T2DM.

  • As a result of the obesity epidemic, classifying a young patient presenting with diabetes is increasingly difficult. If doubt exists over the type of diabetes in a symptomatic patient, insulin therapy and referral for specialist input is the safest management strategy.

  • Autoantibodies are useful at diagnosis, but do not provide a definitive diagnosis.

  • T2DM in younger adults is associated with other features of insulin resistance such as acanthosis nigricans, obesity, hyperlipidaemia, hypertension and polycystic ovarian syndrome.

  • Unlike in T1DM, microvascular complications such as microalbuminuria and retinopathy occur early in the natural history of T2DM in young adults. Therefore, screening for microvascular complications should be initiated at diagnosis.

  • Macrovascular outcomes in young people with T2DM have yet to be realised, but the constellation of risk factors commonly encountered in this group suggest they are at extremely high risk.

  • The use of teratogenic drugs should be avoided in young women who may become pregnant.

Current research questions

  • What is the natural history of type 2 diabetes (T2DM) in younger adults, in terms of β cell function and regenerative capacity?

  • What are the long-term implications of a diagnosis of T2DM in younger adults?

  • What is the role of newer therapies such as incretin mimetics in this group?

  • How can we engage younger adults with T2DM in their care and self-management?

Key references

▶ Alberti G, Zimmet P, Shaw J, et al. Type 2 diabetes in the young: the evolving epidemic: the international diabetes federation consensus workshop. Diabetes Care 2004;27:1798–811.

▶ Shield JP, Lynn R, Wan KC, et al. Management and 1 year outcome for UK children with type 2 diabetes. Arch Dis Child 2009;94:206–9.

▶ Liu LL, Lawrence JM, Davis C, et al. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth Study. Pediatr Diabetes 2010;11:4–11.

▶ Rosenbloom AL, Silverstein JH, Amemiya S, et al. Type 2 diabetes in children and adolescents. Pediatr Diabetes 2009;10(Suppl 12):17–32.

▶ Franks PW, Hanson RL, Knowler WC, et al. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 2010;362:485–93.

Answers

  1. A (T); B (T); C (F); D (T); E (T)

  2. A (T); B (F); C (F); D (F); E (T)

  3. A (T); B (T); C (F); D (T); E (T)

  4. A (T); B (F); C (T); D (T); E (T)

  5. A (T); B (T); C (T); D (F); E (T)

References

Footnotes

  • Competing interests MJD has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lily, Sanofi Aventis, MSD and Novo Nordisk. KK has received funds for research, honoraria for speaking at meetings and or served on advisory boards for Astra Zeneca, GSK, Lily, Novartis, Pfizer, Servier, Sanofi Aventis, MSD and Novo Nordisk. MJD and KK are advisors to the UK Department of Health for the NHS Health Checks Programme. All other authors have nothing to declare.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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