548679

research-article2014
TAJ0010.1177/2040622314548679Therapeutic Advances in Chronic DiseaseE Wilmot and I Idris

Therapeutic Advances in Chronic Disease Review

Early onset type 2 diabetes: risk factors,

Ther Adv Chronic Dis

2014, Vol. 5(6) 234­–244

clinical impact and management DOI: 10.1177/

2040622314548679

© The Author(s), 2014.

Reprints and permissions:
Emma Wilmot and Iskandar Idris http://www.sagepub.co.uk/
journalsPermissions.nav

Abstract:  Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a
significant impact on the individual, healthcare service delivery and planning. The individuals
are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of
black and minority ethnic (BME) origin and come from a less affluent socioeconomic group.
They have a heightened risk of developing microvascular and macrovascular complications,
often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such,
early and aggressive risk factor management is warranted. Early onset T2DM is complex
and impacts on service delivery with a need for multidisciplinary care of complications and
comorbidities’, in addition to adequate educational and psychological support. This review on
the impact of early onset T2DM provides the latest insights into this emerging epidemic.

Keywords:  management, risk factors, type 2 diabetes

Introduction Eppens et al. 2006]. The impact on service deliv- Correspondence to:
Emma Wilmot, MB ChB
In the past three decades there has been a pro- ery is also substantial with a need to recognize BSc (hons) MRCP PhD
gressive increase in the prevalence of early onset and cater for the complexity and specific needs of Department of Diabetes
& Endocrinology, Royal
type 2 diabetes mellitus (T2DM) [González et al. individuals with early onset T2DM, in addition to Derby Hospital, Uttoxeter
2009; Mokdad et al. 2000]. T2DM was once con- planning for the expansion of services such as Road, Derby, UK
emma.g.wilmot@gmail.
sidered a disease of older adults but the age of specialist diabetes antenatal services. From a soci- com
diagnosis is falling and it is now increasingly diag- etal perspective, the costs are huge, with estimates Iskandar Idris, DM FRCP
Royal Derby Hospital
nosed in adolescents and young adults to the suggesting that the direct and indirect cost of and Division of Medical
extent that T2DM will soon become the predomi- T2DM for 2010–2011 in the UK was approxi- Sciences & Graduate Entry
Medicine, University of
nant form of diabetes in some ethnic groups mately £21 billion. This is estimated to rise in real Nottingham, Nottingham,
[Alberti et  al. 2004; Braun et  al. 1996; Dabelea terms to £35.6 billion in 2035–2036 [Hex et al. UK
et  al. 2009; Drake et  al. 2002; Kitagawa et  al. 2012]. This paper aims to explore the impact of
1998; Koopman et  al. 2005; Sharp et  al. 2008]. early onset T2DM for the individual in terms of
An inverse relationship exists between body mass complications and health service planning.
index (BMI) and the age of onset of T2DM
[Hillier and Pedula, 2001] with severe weight gain
<40 years associated with a higher risk of T2DM Definition
[Schienkiewitz et al. 2006]. Available data tend to separate early onset T2DM
into the paediatric (<19 years) and adult (>19
The impact of early onset T2DM is extensive. years) populations. However, there is a contin-
The individuals are likely to be obese, have a mul- uum of risk associated with an earlier diagnosis
tigenerational family history of T2DM, lead a and this distinction, while useful for service provi-
sedentary lifestyle, be of black or minority ethnic sion, fails to recognize the potential for poorer
(BME) origin and come from a socially deprived outcomes in patients diagnosed in their third and
group [Feltbower et al. 2003; Haines et al. 2007]. fourth decades of life. For instance a diagnosis of
They have a heightened risk of the premature T2DM <45 years is associated with a 14-fold
development of microvascular and macrovascular increase in the risk of a myocardial infarct [hazard
complications, in addition to psychological mor- ratio (HR) 14.0, 95% confidence interval (CI)
bidity, during their working life [Dean et al. 2002; 6.2–31.4], substantially greater than the 4-fold

234 http://taj.sagepub.com

increase (HR 3.7, p < 0.001) in those diagnosed
>45 years [Hillier and Pedula, 2003].
Furthermore, the cutoff of 45 years is important
because this captures women with T2DM who
are of child bearing age, a particularly high risk
state which needs to be considered in both man-
agement strategies and service delivery.
Recognizing that there is a paucity of data from
the 19–45 year-old age group, this review presents
available data from across the age ranges, defining
early onset T2DM as <45 years.
Epidemiology
Many Western countries have witnessed an
increase in the prevalence of early onset T2DM.
New York experienced a 10-fold increase in
T2DM in children between 1990 and 2000
[Grinstein et al. 2003]. In the UK there was an
eightfold increase in prescriptions for oral glu-
cose lowering therapy between 1998 and 2005
[Hsia et al. 2009]. The prevalence of T2DM in
this study was estimated at 1.9/100,000, almost
10 times higher than the first UK report of
T2DM in adolescents in 2000 of 0.21/100,000
[Ehtisham et al. 2004]. Adult diabetes specialist
services in the UK have witnessed similar
increases in early onset, with T2DM accounting
for 5% of the diabetes population <30 years in
2003, increasing to 12% by 2006 [Feltbower
et al. 2003; Harron et al. 2011] and extending to
24% of the diabetes population <40 years [Song
et al. 2009]. In Japan the incidence of childhood
onset T2DM doubled between the late 80s and
the early 90s, such that a child presenting with
new onset diabetes in Japan is now statistically
more likely to have T2DM than T1DM
[Kitagawa et  al. 1998]. Early onset T2DM has
been reported in many countries across the
world including Australia, Canada, China,
India, Japan, Mexico and Australia [Braun et al.
1996; Dabelea et  al. 2009; Dean et  al. 2002;
Kitagawa et al. 1998].
Pathophysiology
The pathophysiology of T2DM is complex,
with an alteration in the balance between insu-
lin sensitivity and insulin secretion as the most
important determinant in the development of
T2DM. T2DM results from the gradual fall in
β cell function on a background of insulin
resistance. Adolescents with glucose dysregula-
tion are likely to have more impairment in insu-
lin secretion compared with reduced insulin
http://taj.sagepub.com 235
E Wilmot and I Idris
sensitivity [Bacha et al. 2010]. Studies of insu-
lin secretion and glucose disposal in adoles-
cents with glucose dysregulation have identified
that, in impaired fasting glycaemia (IFG), the
insulin stimulated glucose disposal is normal
but first and second phase insulin secretion are
approximately 50% and 30% lower, respec-
tively. In impaired glucose tolerance (IGT) the
first phase insulin secretion is approximately
40% lower while second phase insulin secretion
is preserved. If IFG and IGT coexist, there is
impairment in both phases – approximately
55% lower first phase insulin and 30% lower
second phase insulin secretion. In T2DM, glu-
cose disposal is impaired by ~30%, first phase
insulin by ~ 75%, and second phase insulin by
~65% compared with children with normal glu-
cose tolerance [Bacha et al. 2010]. Further, the
deterioration in β cell function in youth with
T2DM is more accelerated (~15% per year)
than observed in adults [Gungor et  al. 2004].
As such, those who have a combination of IFG
and IGT are likely to have a higher risk of pro-
gression to T2DM compared with those with
either IFG or IGT in isolation.
Insulin resistance is largely driven by obesity.
However, it is not the degree of obesity which
matters, rather the distribution of fat. A combi-
nation of high intramyocellular lipid content,
increased visceral, decreased subcutaneous and
ectopic liver fat deposition is most likely to
result in glucose dysregulation in both young
adult and paediatric populations [D’Adamo
et al. 2011].
Risk factors
The development of early onset T2DM repre-
sents a complex interplay between genetic and
environmental factors. Table 1 summarizes the
risk factors for developing early onset T2DM.
Overall, the risk factors for T2DM in early onset
are similar to those for late onset T2DM, with the
additional risks factors of female sex and puberty,
which contributes to insulin resistance.
Obesity
The vast majority of those with early onset T2DM
are obese (80–92%) compared with only 56% of
older adults [Hsia et al. 2009; Shield et al. 2009]
with an inverse linear relationship between BMI
and the age at diagnosis of T2DM [Hillier and
Perdula, 2001].
Therapeutic Advances in Chronic Disease 5(6)
Table 1.  Risk factors for type 2 diabetes mellitus in
youth.
Modifiable
• Obesity
•  Low physical activity
•  High sedentary behaviour
•  Socioeconomic status
Nonmodifiable
• Ethnicity (Pima Indian, Hispanic, Asian and
Afro-Caribbean)
•  Family history of type 2 diabetes mellitus
• Puberty
•  Low birth weight
•  Exposure to diabetes mellitus in the uterus
•  Female sex
•  Previous gestational diabetes
Family history
Genetic predisposition plays an important part in
the risk of developing T2DM. Some 84% of UK
adolescents with T2DM have a family history of
T2DM while 56–71% have an affected parent or
sibling [Haines et  al. 2007; Shield et  al. 2009].
While it is likely that a genetic predisposition
increases the risk of early onset T2DM, families
often share a similar environment.
Ethnicity
Internationally, Japanese, Hispanics and Native
Americans have the highest risks of developing
T2DM in childhood [Chan et al. 1993; Dabelea
et al. 2009; Lawrence et al. 2009; Liu et al. 2009].
In the UK, 43–56% are from a black or minority
ethnic origin with prevalence rates of 3.9/100,000
in black and 1.25/100,000 in South Asians com-
pared with the much lower rate of 0.35/100,000
in white children [Haines et al. 2007].
Low physical activity
Physical inactivity is a key factor in the obesity
and diabetes epidemic in younger people.
Clustered metabolic risk (including insulin sensi-
tivity) increases in a dose–response manner with
decreasing physical activity in children aged 9–15
years [Andersen et al. 2006; Ekelund et al. 2007].
This steep decline in physical activity in adoles-
cence is associated with increased weight gain, a
key factor in the development of glucose dysregu-
lation in children [Kimm et al. 2005; Weiss et al.
2005].
236 http://taj.sagepub.com
Clinical outcomes
We and others have shown that patients with
young onset T2DM have a more adverse cardio-
vascular risk profile compared with individuals
with later onset diabetes [Gunathilake et al. 2010;
Song et al. 2009]. In addition, patients with young
onset T2DM have been shown to have a much
higher risk of microvascular complications than
age-matched type 1 diabetes controls, despite
good glycaemic control [Hillier and Pedula, 2003;
Pavkov et  al. 2006; Wong et  al. 2008]. Lifetime
exposure to hyperglycaemia combined with the
presence of multiple cardiovascular risk factors in
young onset T2DM results in a heightened risk of
vascular complications. This is likely to reduce
quality of life, increase morbidity and premature
mortality. This section considers the impact in
terms of microvascular and macrovascular
complications.
Microvascular complications
Nephropathy
Nephropathy in diabetes is a concern not only
because it can result in end stage renal failure but
also because it is associated with cardiovascular
disease. Renal disease is the most frequently
described complication in early onset T2DM. In
the paediatric and adult population, microalbu-
minuria is often present at diagnosis (up to 25%),
increasing to 28–42% at 5 years after diagnosis
and 60% 10 years after diagnosis [Benhalima
et al. 2011; Eppens et al. 2006]. Those diagnosed
<18 years-old have higher rates of microalbumi-
nuria and hypertension than seen in T1DM,
despite a shorter duration of diabetes and lower
HbA1c supporting the hypothesis that early onset
T2DM is a more aggressive form of diabetes
[Eppens et al. 2006].
End stage renal failure starts to manifest approxi-
mately 10 years after the diagnosis of early onset
T2DM [Dart et  al. 2014]. Pima Indians, diag-
nosed with T2DM <20 years, have a five-fold
increase in the risk of developing end stage renal
failure in middle age compared with T1DM while
Japanese data report a significantly higher cumu-
lative incidence of nephropathy in younger adults
diagnosed with T2DM under the age of 30 years
compared with type 1 diabetes mellitus (T1DM)
(44 versus 20%, p < 0.0001) [Pavkov et al. 2006;
Yokoyama et al. 2000]. A large Canadian dataset
(<18 years-old) more recently reported a 4-fold
increased risk of renal failure compared with

T1DM counterparts and a 23-fold increase com-
pared with control subjects [Dart et  al. 2012].
After 20 years of follow up, endstage renal failure
was present in up to 50% of those diagnosed with
T2DM in adolescence, substantially worse than
in the T1DM group [Dart et al. 2012]. These data
suggest that there are inherent differences in the
renal risk between T2DM and T1DM in youth.
Interestingly, systolic hypertension was not a risk
factor in the Dart cohort, while renin angiotensin
aldosterone system (RAAS) pathway inhibition
was (15.8 fold increased risk of renal failure)
[Dart et  al. 2012]. While this may reflect con-
founding from disease severity, it is important to
reflect on the fact that, despite the benefits seen in
the older population with T2DM, we do not yet
have evidence of benefit from RAAS blockade in
the younger population.
Neuropathy
A range of small cross-sectional studies have
reported high rates (up to 57%) of neuropathy in
paediatric T2DM populations [Dart et  al. 2014;
Karabouta et  al. 2008; Paisey et  al. 2009]. The
definition of neuropathy and the testing methods
employed often varies. For instance, 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 periph-
eral neuropathy [Karabouta et  al. 2008]. This
compares with a large study of adolescents with
T2DM (n = 342) and T1DM (n = 1011) which
found peripheral neuropathy (diagnosis based on
disease coding) in 7.6% of the T2DM group and
5% of the T1DM group [Dart et  al. 2014].
Despite these limitations, a consistent message
emerging from these studies is that neuropathy
develops earlier in T2DM than T1DM. This
aggressive course can result in foot ulceration as
early as 2 years after diagnosis and amputation
after 10 years [Dart et al. 2014; Paisey et al. 2009].
Retinopathy
Reported rates of retinopathy in early onset
T2DM varies considerably in the literature
depending on the study methods used (4–40%)
[Eppens et al. 2006; Krakoff et al. 2003; Okudaira
et al. 2000; Pavkov et al. 2006; Scott et al. 2006;
Yokoyama et  al. 1998; TODAY Study Group,
2013]. Early onset T2DM can be associated with
the premature development of retinopathy which
http://taj.sagepub.com 237
E Wilmot and I Idris
is more severe than seen in T1DM. 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
compared with T1DM both at diagnosis and fol-
low up 10 years on [Henricsson et  al. 2003].
Detailed retinal assessment of adolescents with
T1DM and T2DM has identified subclinical
structural and functional retinal abnormalities
which are more pronounced in the T2DM group
compared with the T1DM group, despite a
shorter duration of T2DM (2.1 versus 5.7 years)
[Bronson-Castain et al. 2012].
Cardiovascular morbidity and mortality
Cardiovascular risk markers are often present in
early onset T2DM. At diagnosis, 26% of adoles-
cents have hypertension, increasing to 50% by the
fourth decade [Benhalima et  al. 2011; TODAY
Study Group et  al. 2012]. Research has found
that 80% of adolescents have a low high-density
lipoprotein level and 10% have elevated triglycer-
ides at diagnosis, a finding which tends to pro-
gress rather than improve with follow up [Bell
et  al. 2009; Eppens et  al. 2006; TODAY Study
Group et  al. 2012; Upchurch et  al. 2003;
Zdravkovic et  al. 2004]. By the fourth decade,
those with early onset T2DM in the UK (mean
age 34 years) have a cardiovascular risk profile
(overweight, hyperlipidaemia, hypertension) simi-
lar to that of an older adult with T2DM (mean
age 67 years) [Gunathilake et al. 2010]. Surrogate
markers also identify heightened risk: higher aor-
tic pulse wave velocity, aortic stiffness and greater
carotid-intima-media thickness in adolescence
[Gungor et  al. 2005; Wadwa et  al. 2010; Urbina
et al. 2009] in addition to the presence of diastolic
dysfunction by the fourth decade [Wilmot et  al.
2014]. There is concern that this lifetime expo-
sure to risk will culminate in adverse cardiovascu-
lar outcomes during working lives. Despite this,
only 1 in 5 patients with T2DM in paediatric clin-
ics have blood pressure recorded, suggesting that
physicians may underestimate the risk in early
onset T2DM. This is further reflected in the con-
sistent undertreatment of both hypertension and
hyperlipidaemia in both paediatric and young
adult groups [Benhalima et al. 2011; Shield et al.
2009].
Because early onset T2DM is a relatively new
phenomenon, having only been recognized in the
past few decades, cardiovascular outcome
Therapeutic Advances in Chronic Disease 5(6)
follow-up data are limited. A 9-year follow up of
69 First Nation Canadians adolescents with
T2DM demonstrated a striking mortality rate of
9%. Of the remaining survivors, 35% developed
microalbuminuria, 45% had hypertension and
6% were on dialysis [Dean et al. 2002]. We also
know that those diagnosed with T2DM <45 years
have a 14-fold increased risk of a myocardial
infarct compared with a 4-fold increase in those
diagnosed >45 years [Hillier and Pedula, 2003].
A modelling study has estimated that T2DM
diagnoses between 15–24 years will be associated
with a 15-year reduction in life expectancy and,
for some, the development of severe chronic com-
plications in their fifth decade [Rhodes et  al.
2012].
Nonalcoholic fatty liver disease
Nonalcoholic fatty liver disease (NAFLD) is an
important marker of insulin resistance. It is the
most common liver abnormality seen in children
and is present in approximately 50% of children
with T2DM [Bloomgarden, 2007]. A 20-year fol-
low-up study of adolescents with NAFLD (with-
out diabetes) reported that 6% died or required a
liver transplant with a standardized morality ratio
of 13.6 [Feldstein et al. 2009]. This would suggest
that the combination of T2DM and NAFLD
developing early in life is likely to lead to substan-
tial morbidity and mortality.
T2DM and pregnancy
There has been a substantial increase in the num-
ber of women with early onset T2DM attending
maternity services. A third of the women in the
UK Confidential Enquiry into Maternal and
Child Health (CEMACH) report had T2DM
[CEMACH, 2007]. T2DM in pregnancy has a
significant impact on the mother, the fetus and
service provision. It is associated with a number
of risks for both the mother and fetus, with out-
comes for women with T2DM are just as poor as
for women with T1DM. These include miscar-
riage, preterm labour, macrosomia, birth injury,
neonatal hypoglycaemia and stillbirth in addition
to a 2-fold increase in the rate of congenital mal-
formations and a 3-fold increase in the risk of
perinatal mortality [CEMACH, 2007]. These
risks are likely to be even higher in adolescents
with T2DM. A group of Canadian adolescents
with T2DM were followed up for 10 years and of
those who became pregnant, 38% experienced
pregnancy loss [Dean et  al. 2002]. These risks
238 http://taj.sagepub.com
associated with diabetes and pregnancy can be
minimized through meticulous glycaemic control
(HbA1c <6.1%), high dose folic acid (5 mg a
day) combined with close monitoring of the
mother and fetus [NICE, 2008]. Unfortunately
women with T2DM are less likely to have prepreg-
nancy counselling, preconception folic acid or a
test of glycaemic control in the 6 months before
conception compared with women with T1DM
[CEMACH, 2007]. The increasing number of
women of child bearing age who have T2DM has
a substantial impact on service planning and
delivery. They represent complex cases that
require an intensive multidisciplinary approach
both in terms of preconception and antenatal care
to minimize risk.
Psychological aspects
The psychological burden on youth with T2DM
is great. They not only need to strive for excel-
lent glucose control and weight loss, but also the
need to take multiple medications and cope with
complications and comorbidities at an early
stage in life. The combination of increased body
weight, body dissatisfaction, previous dieting
and a history of depression can result in binge
eating disorders [Pinhas-Hamiel et  al. 2013].
Two-thirds report severe diabetes-related dis-
tress while more than a quarter have impaired
general emotional well-being [Browne et  al.
2013]. Many live in fear of disclosure of their
condition and have higher rates of depression
and report lower quality of life than youth with
T1DM [Brouwer et al. 2012; Hood et al. 2014].
The above issues impact on self management
and will require further research to enable a bet-
ter understanding of how we best support
younger people living with T2DM.
Management
Glucose lowering therapies
The majority of patients with early onset T2DM
<45 years will have access to the wide array of
glucose lowering therapies currently approved for
adult use, including gliptins and glucagon-like
peptide-1 (GLP-1) analogues. Such agents would,
in theory, benefit those with early onset T2DM,
who tend to have a higher BMI at diagnosis than
older adults. However, the evidence base under-
pinning these agents is often from an older adult
population and available data do not describe the
clinical response in younger adults.

Drug licensing restrictions apply to the paediatric
population and warrant special consideration.
Currently, metformin and insulin are the only
drugs approved for use in the paediatric popula-
tion with T2DM. Metformin inhibits gluconeo-
genesis and promotes peripheral glucose uptake,
improving glucose sensitivity. Few trials have
assessed traditional oral hypoglycaemic agents in
early onset T2DM. In 2002 a multi-centre 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 reduc-
tion in HbA1c of 1.2% and a 3.6 mmol/l reduc-
tion in fasting glucose compared with the placebo
arm [Jones et al. 2002]. Glimepiride, a sulphony-
lurea, promotes insulin secretion. In 2007 a single
blind multi-national study reported that glime-
piride reduced HbA1c similarly to metformin in
263 young people with T2DM (mean age 13.8
years). However, the use of glimepiride was asso-
ciated with a 1.97 kg weight gain compared with
only 0.55 kg in the metformin group. Safety pro-
files of both drugs were comparable over the
26-week follow-up period [Gottschalk et  al.
2007].
The TODAY trial follows on from these prelimi-
nary trials and is the largest therapeutic trial to be
conducted in a large cohort of adolescents with
T2DM [TODAY Study Group et  al. 2012]. In
this 4-year follow-up randomized controlled trial,
those recently diagnosed with T2DM were ran-
domly assigned to either metformin alone, met-
formin and a lifestyle intervention, or metformin
plus rosiglitazone. The addition of rosiglitazone
but not the lifestyle intervention was superior to
metformin alone [TODAY Study Group et  al.
2012] (Table 2). The metformin treatment failure
rate was higher than is seen in older adults with
T2DM and suggests that younger adults with
T2DM are likely to require more aggressive poly-
pharmacy early in the course of their disease
[TODAY Study Group et al. 2012]. This trial also
suggests that the benefits of lifestyle interventions
in adolescents with T2DM may be limited, but
this requires more detailed exploration.
Cardiovascular risk management
In terms of cardiovascular risk management, life-
style interventions to reduce weight and increase
exercise are advocated. If hyperlipidaemia or
hypertension persists, then a statin or angiotensin
converting enzyme inhibitor should be initiated
[Rosenbloom et  al. 2009]. However, there have
http://taj.sagepub.com 239
E Wilmot and I Idris
Table 2.  Results from the TODAY trial [TODAY Study
Group et al. 2012].
Intervention Failure
rate
Metformin alone 51.7%
Metformin + lifestyle 46.6%
Metformin + rosiglitazone 38.6%
Pairwise test p value
Metformin + lifestyle versus metformin 0.015
Metformin versus metformin + 0.006
rosiglitazone
Metformin versus metformin + lifestyle 0.17
The study compared the efficacy of three treatment regi-
mens (metformin 1000 mg twice daily alone, a metformin
+ lifestyle intervention programme focusing on weight
loss through eating and activity behaviours, and metfor-
min + rosiglitazone 4 mg twice daily) to achieve durable
glycaemic control in children and adolescents with early-
onset type 2 diabetes. The primary outcome was loss of
glycaemic control, defined as a glycated haemoglobin
level of at least 8% for 6 months or sustained metabolic
decompensation requiring insulin. Results are described
in the text.
been no pharmacotherapeutic outcome studies of
such agents in early onset T2DM. This is perhaps
reflected in clinical practice with the consistent
under treatment of hyperlipidaemia and hyper-
tension [Benhalima et al. 2010]. This is more so
the case in the female population, perhaps due to
concerns about the possibility of conception.
Significantly fewer women are treated for hyper-
tension (22% versus 43%, p  <  0.01) and hyper-
cholesterolaemia (16% versus 43%, p  <  0.01)
than men, despite similar rates of hypercholester-
olaemia and hypertension [Benhalima et  al.
2010]. Overall, early onset T2DM is an aggressive
condition which will require aggressive manage-
ment of blood pressure, lipids, glycaemic control
and weight.
Bariatric surgery
Bariatric surgery is capable of inducing diabetes
remission in adults with T2DM, in addition to
considerable weight loss [Schauer et  al. 2014].
Restrictive bariatric procedures include gastric
banding and sleeve gastrectomy while malabsorp-
tive procedures include gastric bypass and bilio-
pancreatic diversion. Malabsorptive procedures
are superior in achieving remission of T2DM.
Guidelines for the safe and effective delivery of
bariatric surgical care for adolescents do exist and
bariatric surgery has been shown to reverse
Therapeutic Advances in Chronic Disease 5(6)
T2DM in some severely obese children
[Al-Qahtani, 2007; Inge et  al. 2009; Michalsky
et al. 2011]. Although surgery might be viewed as
an extreme measure, in view of the accelerated
development of multiple complications in early
onset T2DM, it may be an option worth consider-
ing in selected cases. Further research in this area
is required.
Structured education
Self management is the cornerstone of diabetes
care. In younger adults with T2DM, lack of moti-
vation, feeling burned out and being time poor
have been identified as some of the key barriers to
self management. Few participate in structured
diabetes education [Browne et  al. 2013]. This is
perhaps a reflection of the fact that existing edu-
cation courses, which were designed for older
adults, do not meet the specific needs of those
with early onset T2DM [Browne et al. 2013]. To
overcome these issues, a course written specifi-
cally for and attended by groups of younger adults
with T2DM would be more appropriate [Brouwer
et al. 2012]. Furthermore, it has been identified
that even for those who have completed struc-
tured education courses, there is a high level of
need for ongoing learning [Richards et al. 2013].
This will require the continued assessment of
learning needs, follow-up education and behav-
ioural approaches for these high risk individuals
[Richards et al. 2013].
Implications for service delivery and policy
Those with early onset T2DM represent a high
risk group with high needs for effective manage-
ment and support. At present, many of these indi-
viduals are cared for by generalists in the
community. Given the complexity, the subopti-
mal response to available therapies and the
heightened risk of complications it could be
argued that these individuals should be cared for
in a multidisciplinary specialist clinic with access
to specialist psychological, dietary and bariatric
support. Structured education is a cost effective
and acceptable way of empowering patients to
optimize their self-management skills. There is a
need to develop a curriculum which meets the
needs of those with early onset T2DM, with spe-
cific focus on relevant topics such as preconcep-
tion care, the impact of family members with
T2DM, body image, self-esteem, recognizing and
managing depression, etc. Follow-up education
also needs to be developed and could embrace
240 http://taj.sagepub.com
currently available technologies such as internet
forums and social media.
Of course, the ideal solution would be the preven-
tion of T2DM in young people. Although beyond
the scope of this paper, tackling the obesity epi-
demic will require combined efforts on behalf of
individuals, healthcare professionals and organi-
zations, and government to make changes to
reduce the prevalence of obesity. Policies on food
marketing, exercise, structured environment,
transportation, physical activity in schools and
work will need to change to allow this to happen.
In the meantime there is a need to identify and
screen those at risk of T2DM so that intensive
lifestyle interventions can delivered in an attempt
to reverse, or at least prevent, weight gain and the
development of T2DM [NICE, 2013].
Conclusion
Early onset T2DM is an increasingly common
problem which leads to the premature develop-
ment of microvascular and macrovascular com-
plications. Although we do not yet have a full
understanding of the natural history of this condi-
tion, the impact on the individual, service delivery
and finances will be substantial. Those with early
onset T2DM represent a high risk group with
specific issues and needs. They merit an aggres-
sive and supportive management in a multidisci-
plinary setting to prevent the development of
significant morbidity during their most produc-
tive years.
Conflict of interest statement
The authors declare no conflict of interest in pre-
paring this article.
Funding
This research received no specific grant from any
funding agency in the public, commercial, or not-
for-profit sectors.
References
Alberti, G., Zimmet, P., Shaw, J., Bloomgarden, Z.,
Kaufman, F., Silink, M. et al. (2004) Type 2 diabetes
in the young: the evolving epidemic: the international
diabetes federation consensus workshop. Diabetes Care
27: 1798–1811.
Al-Qahtani, A. (2007) Laparoscopic adjustable gastric
banding in adolescent: safety and efficacy. J Pediatr
Surg 42: 894–897.

Andersen, L., Harro, M., Sardinha, L., Froberg, K.,
Ekelund, U., Brage, S. et al. (2006) Physical activity
and clustered cardiovascular risk in children: a cross-
sectional study (The European Youth Heart Study).
Lancet 368: 299e304.
Bacha, F., Lee, S., Gungor, N. and Arslanian, S.
(2010) From pre-diabetes to type 2 diabetes in obese
youth:pathophysiological characteristics along the
spectrum of glucose dysregulation. Diabetes Care 33:
2225–2231.
Bell, R., Mayer-Davis, E., Beyer, J., D’Agostino, R.,
Lawrence, J., Linder, B. et al. (2009) Diabetes in
non-Hispanic white youth: prevalence, incidence, and
clinical characteristics: the SEARCH for Diabetes in
Youth Study. Diabetes Care 32(Suppl. 2): S102–11.
Benhalima, K., Song, S., Wilmot, E., Khunti, K.,
Gray, L., Lawrence, I. et al. (2011) Characteristics,
complications and management of a large multiethnic
cohort of younger adults with type 2 diabetes. Prim
Care Diabetes 5: 245–50.
Benhalima, K., Wilmot, E., Yates, T., Khunti, K.,
Lawrence, I. and Davies, M. (2010) Challenges in
the management of the younger adult with Type 2
Diabetes (T2DM). Diabetic Medicine 27(Suppl. 1):
P161.
Bloomgarden, Z. (2007) Nonalcoholic fatty liver
disease and insulin resistance in youth. Diabetes Care
30: 1663–1669.
Braun, B., Zimmermann, M., Kretchmer, N., Spargo,
R., Smith, R. and Gracey, M. (1996) Risk factors
for diabetes and cardiovascular disease in young
Australian aborigines. A 5-year follow-up study.
Diabetes Care 19: 472–479.
Bronson-Castain, K., Bearse, M., Jr., Neuville, J.,
Jonasdottir, S., King-Hooper, B., Barez, S. et al.
(2012) Early neural and vascular changes in the
adolescent type 1 and type 2 diabetic retina. Retina
32: 92–102.
Browne, J., Scibilia, R. and Speight, J. (2013) The
needs, concerns, and characteristics of younger
Australian adults with Type 2 diabetes. Diabet Med
30: 620–626.
Brouwer, A., Salamon, K., Olson, K., Fox, M.,
Yelich-Koth, S., Fleischman, K. et al. (2012)
Adolescents and type 2 diabetes mellitus: a qualitative
analysis of the experience of social support. Clin
Pediatr (Phila) 51: 1130–1139.
CEMACH (2007) Diabetes in pregnancy: are we
providing the best care? Findings of a national enquiry:
England, Wales and Northern Ireland. London:
Confidential Enquiry into Maternal and Child Health.
Chan, J., Cheung, C., Swaminathan, R., Nicholls,
M. and Cockram, C. (1993) Obesity, albuminuria
and hypertension among Hong Kong Chinese with
http://taj.sagepub.com 241
E Wilmot and I Idris
non-insulin-dependent diabetes mellitus (NIDDM).
Postgrad Med J 69: 204e10.
Dabelea, D., DeGroat, J., Sorrelman, C., Glass,
M., Percy, C., Avery, C. et al. (2009) Diabetes in
Navajo youth: prevalence, incidence, and clinical
characteristics: the SEARCH for Diabetes in Youth
Study. Diabetes Care 32(Suppl. 2): S141–7.
D’Adamo, E. and Caprio, S. (2011) Type 2 diabetes
in youth: epidemiology and pathophysiology. Diabetes
Care 34(Suppl. 2): S161–5.
Dart, A., Martens, P., Rigatto, C., Brownell, M.,
Dean, H. and Sellers, E. (2014) Earlier onset of
complications in youth with type 2 diabetes. Diabetes
Care 37: 436–443.
Dart, A., Sellers, E., Martens, P., Rigatto, C.,
Brownell, M. and Dean, H. (2012) High burden of
kidney disease in youth-onset type 2 diabetes. Diabetes
Care 35: 1265–1271.
Dean, H. and Flett, B. (2002) Natural history of
type 2 diabetes diagnosed in childhood: long term
follow-up in young adult years. Diabetes 51(Suppl. 2):
A24.
Drake, A., Smith, A., Betts, P., Crowne, E. and
Shield, J. (2002) Type 2 diabetes in obese white
children. Arch Dis Child 86: 207–208.
Ehtisham, S., Hattersley, A., Dunger, D. and Barrett,
T. (2004) British Society for Paediatric Endocrinology
and Diabetes Clinical Trials Group. First UK survey
of paediatric type 2 diabetes and MODY. Arch Dis
Child 89: 526–529.
Ekelund, U., Franks, P., Sharp, S., Brage, S. and
Wareham, N. (2007) Increase in physical activity
energy expenditure is associated with reduced
metabolic risk independent of change in fatness and
fitness. Diabetes Care 30: 2101–6.
Eppens, M., Craig, M., Cusumano, J., Hing, S.,
Chan, A., Howard, N. et al. (2006) Prevalence of
diabetes complications in adolescents with type 2
compared with type 1 diabetes. Diabetes Care 29:
1300–1306.
Feldstein, A., Charatcharoenwitthaya, P.,
Treeprasertsuk, S., Benson, J., Enders, F. and
Angulo, P. (2009) The natural history of non-
alcoholic fatty liver disease in children: a follow-up
study for up to 20 years. Gut 58: 1538–1544.
Feltbower, R., McKinney, P., Campbell, F.,
Stephenson, C. and Bodansky, H. (2003) Type 2 and
other forms of diabetes in 0–30 year olds: a hospital
based study in Leeds, UK. Arch Dis Child 88: 676–679.
González, E., Johansson, S., Wallander, M. and
Rodríguez, L. (2009) Trends in the prevalence
and incidence of diabetes in the UK: 1996–2005. J
Epidemiol Community Health 63: 332–336.
Therapeutic Advances in Chronic Disease 5(6)
Gottschalk, M., Danne, T., Vlajnic, A. and Cara, J.
(2007) Glimepiride versus metformin as monotherapy
in pediatric patients with type 2 diabetes. Diabetes
Care 30: 790–794.
Grinstein, G., Muzumdar, R., Aponte, L., Vuguin,
P., Saenger, P. and DiMartino-Nardi, J. (2003)
Presentation and 5-year follow-up of type 2 diabetes
mellitus in African-American and Caribbean-Hispanic
adolescents. Horm Res 60: 121–126.
Gunathilake, W., Song, S., Sridharan, S., Fernando,
D. and Idris, I. (2010) Cardiovascular and metabolic
risk profiles in young and old patients with type 2
diabetes QJM 103: 881–884.
Gungor, N. and Arslanian, S. (2004) Progressive
beta cell failure in type 2 diabetes mellitus of youth. J
Pediatr 44: 656–659.
Gungor, N., Thompson, T., Sutton-Tyrrell, K.,
Janosky, J. and Arslanian, S. (2005) Early signs of
cardiovascular disease in youth with obesity and type
2 diabetes. Diabetes Care 28: 1219–1221.
Haines, L., Wan, K., Lynn, R., Barrett, T. and
Shield, J. (2007) Rising incidence of type 2 diabetes in
children in the UK. Diabetes Care 30: 1097–1101.
Harron, K., Feltbower, R., McKinney, P., Bodansky,
H., Campbell, F. and Parslow, R. (2011) Rising rates
of all types of diabetes in south Asian and non-south
Asian children and young people aged 0–29 years in
West Yorkshire, UK, 1991–2006. Diabetes Care 34:
652–654.
Henricsson, M., Nystrom, L., Blohme, G., Ostman,
J., Kullberg, C., Svensson, M. et al. (2003) The
incidence of retinopathy 10 years after diagnosis in
young adult people with diabetes: results from the
nationwide population-based Diabetes Incidence
Study in Sweden (DISS). Diabetes Care 26: 349–354.
Hex, N., Bartlett, C., Wright, D., Taylor, M. and
Varley, D. (2012) Estimating the current and future
costs of type 1 and type 2 diabetes in the UK,
including direct health costs and indirect societal and
productivity costs. Diabet Med 29: 855–862.
Hillier, T. and Pedula, K. (2001) Characteristics
of an adult population with newly diagnosed type 2
diabetes. The relation of obesity and age of onset.
Diabetes Care 24: 1522–1527.
Hillier, T. and Pedula, K. (2003) Complications in
young adults with early-onset type 2 diabetes: losing
the relative protection of youth. Diabetes Care 26:
2999–3005.
Hood, K., Beavers, D., Yi-Frazier, J., Bell, R.,
Dabelea, D., McKeown, R. et al. (2014) Psychosocial
burden and glycemic control during the first 6
years of diabetes: results from the SEARCH for
Diabetes in Youth Study. J Adolesc Health S1054–
139X(14)00149–9.
242 http://taj.sagepub.com
Hsia, Y., Neubert, A., Rani, F., Viner, R.,
Hindmarsh, P. and Wong, I. (2009) An increase in
the prevalence of type 1 and 2 diabetes in children
and adolescents: results from prescription data from a
UK general practice database. Br J Clin Pharmacol 67:
242–249.
Inge, T., Miyano, G., Bean, J., Helmrath, M.,
Courcoulas, A., Harmon, C. et al. (2009) Reversal
of type 2 diabetes mellitus and improvements in
cardiovascular risk factors after surgical weight loss in
adolescents. Pediatrics 123: 214–222.
Jones, K., Arslanian, S., Peterokova, V., Park, J.
and Tomlinson, M. (2002) Effect of metformin in
pediatric patients with type 2 diabetes. Diabetes Care
25: 89–94.
Karabouta, Z., Barnett, S., Shield, J., Ryan, F. and
Crowne, E. (2008) Peripheral neuropathy is an early
complication of type 2 diabetes in adolescence. Pediatr
Diabetes 9: 110–114.
Kimm, S., Glynn, N., Obarzanek, E., Kriska, A.,
Daniels, S., Barton, B. et al. (2005) Relation between
the changes in physical activity and body-mass index
during adolescence: a multicentre longitudinal study.
Lancet 366: 301–307.
Kitagawa, T., Owada, M., Urakami, T. and
Yamauchi, K. (1998) Increased incidence of non-
insulin dependent diabetes mellitus among Japanese
schoolchildren correlates with an increased intake of
animal protein and fat. Clin Pediatr 37: 111–115.
Koopman, R., Mainous, A., Diaz, V. and Geesey, M.
(2005) Change in age at diagnosis of type 2 diabetes
mellitus in the United States, 1988 to 2000. Ann Fam
Med 3: 60–63.
Krakoff, J., Lindsay, R., Looker, H., Nelson, R.,
Hanson, R. and Knowler, W. (2003) Incidence of
retinopathy and nephropathy in youth onset compared
with adult-onset type 2 diabetes. Diabetes Care 26:
76–81.
Lawrence, J., Mayer-Davis, E., Reynolds, K., Beyer,
J., Pettitt, D., D’Agostino, R., Jr. et al. (2009)
Diabetes in Hispanic American youth: prevalence,
incidence, demographics, and clinical characteristics:
the SEARCH for Diabetes in Youth Study. Diabetes
Care 32(Suppl. 2): S123–S132.
Liu, L., Yi, J., Beyer, J., Mayer-Davis, E., Dolan,
L., Dabelea, D. et al. (2009) Type 1 and type 2
diabetes in Asian and Pacific Islander U.S. youth: the
SEARCH for Diabetes in Youth Study. Diabetes Care
32(Suppl. 2): S133e40.
Michalsky, M., Kramer, R., Fullmer, M., Polfuss,
M., Porter, R., Ward-Begnoche, W. et al. (2011)
Developing criteria for pediatric/adolescent
bariatric surgery programs. Pediatrics 128(Suppl.
2): S65–S70.

Mokdad, A., Bowman, B., Engelgau, M. and Vinicor,
F. (2000) Diabetes trends in the U.S.: 1990–1998.
Diabetes Care 23: 1278–1283.
NICE (2008) Diabetes in pregnancy: management of
diabetes and its complications from pre-conception to
the postnatal period. NICE Guidelines CG63. London:
National Institute for Health and Clinical Excellence.
Available at: http://guidance.nice.org.uk/CG63
(accessed 5 June 2014).
NICE (2012) Preventing type 2 diabetes: risk
identification and interventions for individuals at
high risk. NICE Guidelines PH38. London: National
Institute for Health and Clinical Excellence. Available
at: http://www.nice.org.uk/PH38 (accessed 5 June
2014).
Okudaira, M., Yokoyama, H., Otani, T., Uchigata,
Y. and Iwamoto, Y. (2000) Slightly elevated blood
pressure as well as poor metabolic control are
risk factors for the progression of retinopathy in
early-onset Japanese type 2 diabetes. J Diabetes
Complications 14:281–287
Paisey, R., Paisey, R., Thomson, M., Bower, L.,
Maffei, P., Shield, J.. et al. (2009) Protection from
clinical peripheral sensory neuropathy in alström
syndrome in contrast to early-onset type 2 diabetes.
Diabetes Care 32: 462–464.
Pavkov, M., Bennett, P., Knowler, W., Krakoff,
J., Sievers, M. and Nelson, R. (2006) Effect of
youth-onset type 2 diabetes mellitus on incidence of
end-stage renal disease and mortality in young and
middle-aged Pima Indians. JAMA 296: 421–426.
Pinhas-Hamiel, O. and Levy-Shraga, Y. (2013)
Eating disorders in adolescents with type 2 and type 1
diabetes. Curr Diabetes Rep 13: 289–297.
Rhodes, E., Prosser, L., Hoerger, T., Lieu, T.,
Ludwig, D. and Laffel, L. (2012) Estimated morbidity
and mortality in adolescents and young adults
diagnosed with type 2 diabetes mellitus. Diabetic Med
29: 453–463.
Richards, D., Larkin, M., Milaszewski, K., Javier,
E., Casey, T. and Grey, M. (2013) Learning needs
of youth with type 2 diabetes. Diabetes Educ 39:
314–319.
Rosenbloom, A., Silverstein, J., Amemiya, S., Zeitler,
P. and Klingensmith, G. (2009) Type 2 diabetes in
children and adolescents. Pediatr Diabetes 10(Suppl.
12): 17–32.
Schauer, P., Bhatt, D., Kirwan, J., Wolski, K.,
Brethauer, S., Navaneethan, S. et al. (2014) Bariatric
surgery versus intensive medical therapy for diabetes—
3-year outcomes. N Engl J Med 370: 2002–2013.
Schienkiewitz, A., Schulze, M., Hoffmann, K.,
Kroke, A. and Boeing, H. (2006) Body mass index
history and risk of type 2 diabetes: results from the
http://taj.sagepub.com 243
E Wilmot and I Idris
European Prospective Investigation into Cancer and
Nutrition (EPIC)–Potsdam Study. Am J Clin Nutr
84: 427–433.
Scott, A., Toomath, R., Bouchier, D., Bruce, R.,
Crook, N., Carroll, D. et al. (2006) First national
audit of the outcomes of care in young people
with diabetes in New Zealand: high prevalence of
nephropathy in Maori and Pacific Islanders. N Z Med
J 119: U2015.
Sharp, P., Brown, B. and Qureshi, A. (2008)
Age at diagnosis of diabetes in a secondary care
population: 1992–2005. Br J Diabetes Vasc Dis 8:
92–95.
Shield, J., Lynn, R., Wan, K., Haines, L. and Barrett,
T. (2009) Management and 1 year outcome for UK
children with type 2 diabetes. Arch Dis Child 94:
206–209.
Song, S. and Hardisty, C. (2009) Early onset type
2 diabetes mellitus: a harbinger for complications in
later years—clinical observation from a secondary care
cohort. QJM 102: 799–806.
TODAY Study Group (2013) Retinopathy in youth
with type 2 diabetes participating in the TODAY
clinical trial. Diabetes Care 36: 1772–1774
TODAY Study Group, Zeitler, P., Hirst, K.,
Pyle, L., Linder, B., Copeland, K. et al. (2012)
A clinical trial to maintain glycemic control in
youth with type 2 diabetes. N Engl J Med 366:
2247–2256.
Wadwa, R., Urbina, E., Anderson, A., Hamman,
R., Dolan, L., Rodriguez, B. et al. (2010) Measures
of arterial stiffness in youth with type 1 and type 2
diabetes: the SEARCH for Diabetes in Youth study.
Diabetes Care 33: 881–886.
Weiss, R., Taksali, S., Tamborlane, W., Burgert,
T., Savoye, M. and Caprio, S. (2005) Predictors of
changes in glucose tolerance status in obese youth.
Diabetes Care 28: 902–909.
Wilmot, E., Leggate, M., Khan, J., Yates, T., Gorely,
T., Bodicoat, D. et al. (2014) Type 2 diabetes mellitus
and obesity in young adults: the extreme phenotype
with early cardiovascular dysfunction. Diabet Med 31:
794–798.
Wong, J., Molyneaux, L., Constantino, M., Twigg,
S. and Yue, D. (2008) Timing Is everything: Age of
OnsetInfluences Long-Term Retinopathy Risk in Type
2 Diabetes, Independent of Traditional Risk Factors.
Diabetes Care 31: 1985–1990.
Upchurch, S., Brosnan, C., Meininger, J.,
Wright, D., Campbell, J., McKay, S. et al. (2003)
Characteristics of 98 children and adolescents
diagnosed with type 2 diabetes by their health care
provider at initial presentation. Diabetes Care 26:
2209.
Therapeutic Advances in Chronic Disease 5(6)
Urbina, E., Kimball, T., McCoy, C., Khoury, P.,
Daniels, S. and Dolan, L. (2009) Youth With Obesity
and Obesity-Related Type 2 Diabetes Mellitus
Demonstrate Abnormalities in Carotid Structure and
Function. Circulation 119: 2913–2919.
Yokoyama, H., Okudaira, M., Otani, T., Sato, A., Miura,
Visit SAGE journals online J., Takaike, H. et al. (2000) Higher incidence of diabetic
http://taj.sagepub.com
nephropathy in type 2 than in type 1 diabetes in early
SAGE journals onset diabetes in Japan. Kidney Int 58: 302–311.
244 http://taj.sagepub.com
Yokoyama, H., Okudaira, M., Otani, T., Watanabe,
C., Takaike, H., Miuira, J. et al. (1998) High
incidence of diabetic nephropathy in early-onset
Japanese NIDDM patients. Risk analysis. Diabetes
Care 21: 1080–1085.
Zdravkovic, V., Daneman, D. and Hamilton, J.
(2004) Presentation and course of Type 2 diabetes
in youth in a large multi-ethnic city. Diabet Med 21:
1144–1148.