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CLINICAL REVIEW: Type 1 Diabetes and Latent
Autoimmune Diabetes in Adults: One End of
the Rainbow
R. David G. Leslie, Rhys Williams, and Paolo Pozzilli
Institute of Cell and Molecular Science (R.D.G.L., P.P.), Queen Mary College, University of London, London E1 4NS, United
Kingdom; University of Wales School of Medicine (R.W.), Swansea SA2 8PP, United Kingdom; and Department of
Endocrinology and Diabetes (P.P.), University Campus Bio-Medico, 83-00155 Rome, Italy
Context: The aim of this review was to explore the pathogenic and
clinical spectrum of type 1 diabetes, which includes a form of adult
onset autoimmune diabetes usually referred to as latent autoimmune
diabetes in adults (LADA). We looked at this entire range of forms of
autoimmune diabetes as a spectrum of genetic and nongenetic envi-
ronmental influences, diabetes-associated immune responses, and
metabolic changes.
Evidence Acquisition: We assessed epidemiological, genetic, im-
munological, and clinical data from major articles on autoimmune
diabetes, including LADA and type 1 diabetes, published since 1992.
Evidence Synthesis: Data analysis of autoimmune diabetes indi-
cates that type 1 diabetes and LADA occupy different poles of the
same spectrum.
Conclusion: Evidence is presented that LADA represents one end of
a rainbow encompassing type 1 diabetes. The clinical nature and
management of autoimmune diabetes poses important therapeutic
questions regarding conventional therapy for hyperglycemia as well
as therapy aiming to protect residual

-cell function. Limiting loss of
endogenous insulin secretion using immunomodulation could be valu-
able, not only for LADA but also for type 1 diabetes. (J Clin Endo-
crinol Metab 91: 1654 –1659, 2006)
TYPE 1 DIABETES RESULTS from the destruction of the
insulin-secreting islet cells by an immune mediated
process. This adverse immune response is induced and pro-
moted by the interaction of genetic and environmental fac-
tors and is one of a group of autoimmune diseases that affect
about 10% of the population in the developed world. Type
1 diabetes used to be defined in terms of the absolute need
for insulin therapy (insulin-dependent diabetes) or, before
that, the age at onset of the disease (juvenile onset diabetes).
These defining features were then abandoned in favor of the
term type 1 diabetes (1) when it became apparent that not
everyone with autoimmune diabetes is either a juvenile or
necessarily exhibits an absolute insulin requirement.
Individuals diagnosed with autoimmune diabetes, i.e. di-
abetes associated with diabetes-associated autoantibodies,
when they are adults may not initially require insulin treat-
ment and have been classified as having latent autoimmune
diabetes of adults (LADA) (2, 3), latent because without
testing for diabetes-associated autoantibodies it would not be
possible to identify these patients as having autoimmune
diabetes and adult because at that time it was suggested that
this form of diabetes was not present in juveniles. This form
of diabetes has also been called slowly progressing insulin-
dependent diabetes (4) or type 1.5 diabetes (5). The aim of this
article was to explore the clinical and pathogenic spectrum
of autoimmune diabetes that extends into and includes
LADA.
LADA is defined by three features including: adult age at
diagnosis, the presence of diabetes-associated autoantibod-
ies, and delay from diagnosis in the need for insulin therapy
to manage hyperglycemia. However, the first and last are not
categorical traits, being dependent on the mode of ascertain-
ment and decision making by physicians. The second feature
lacks disease specificity because it is based on positivity for
autoantibodies found in type 1 diabetes mellitus. In a recent
review (6), it was suggested that LADA patients should be
diagnosed with non-insulin-requiring diabetes at age 30 yr or
older and that age (range 30–70 yr) was also used in a major
European Union initiative (www.actionlada.org); in addi-
tion, both defined LADA to include patients who had 6
months without insulin treatment after diagnosis (6). Other
large studies of autoimmune non-insulin-requiring patients
have included selected cases, cases not taking any pharma-
cological agent, or avoided a definition entirely (7–9). Diffi-
culties with the performance of islet cell and insulin auto-
antibody assays precluded them from being used routinely
in defining LADA. Because insulinoma-associated antigen
(IA)-2 autoantibodies are usually found with glutamic acid
decarboxylase (GAD) autoantibodies but rarely in LADA,
this condition is broadly defined by the presence of GAD
autoantibodies. However, GAD autoantibodies are also
found in type 1 diabetes mellitus, so it follows that using
them in the definition of LADA lacks disease specificity (10).
The epidemiology of LADA is also influenced by geography,
First Published Online February 14, 2006
Abbreviations: GAD, Glutamic acid decarboxylase; HLA, human leu-
kocyte antigen; IA, insulinoma-associated antigen; IAA, insulin auto-
antibody; ICA, islet cell autoantibody; LADA, latent autoimmune dia-
betes in adults.
JCEM is published monthly by The Endocrine Society (http://www.
endo-society.org), the foremost professional society serving the en-
docrine community.
0021-972X/06/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 91(5):1654 –1659
Printed in U.S.A. Copyright © 2006 by The Endocrine Society
doi: 10.1210/jc.2005-1623
1654
on May 9, 2006 jcem.endojournals.orgDownloaded from
genetic susceptibility, environmental factors, gender, and
age at diagnosis. In Northern Europe and North America,
about 5–10% of newly diagnosed non-insulin-requiring di-
abetes patients have LADA, according to the mode of as-
certainment, the sourced population, the age of the patient
(frequency is higher in younger age groups), and the defi-
nition of the disease (5, 6, 10).
LADA at One End of a Spectrum of Genetic
Susceptibility
The epidemiology of autoimmune diabetes including type
1 diabetes is influenced by genetic susceptibility, which mod-
ifies age at onset (6). There is evidence in autoimmune di-
abetes for a continuum of genetic susceptibility, which ex-
tends from a marked effect in childhood-onset type 1
diabetes to the relatively limited effect detected in LADA
(Table 1). Survival analysis estimates that nondiabetic iden-
tical twins of probands diagnosed with type 1 diabetes under
25 yr of age have a 38% probability of developing diabetes,
compared with only 6% for twins of probands diagnosed
later (11–13) (Table 2). Such a remarkably low twin concor-
dance for adult-onset type 1 diabetes implies that the genetic
impact in adult-onset diabetes is limited (14, 15), favoring a
substantial impact of environmental factors. There is an age-
related continuum in diminishing twin concordance, sug-
gesting that the decline in genetic influence is gradual, con-
sistent with a phased influence on a single disease, type 1
diabetes, rather than an age-related step-wise effect resulting
from two distinct diseases. There are, as yet, no twin studies
of LADA. Of genes implicated in the genetic susceptibility to
type 1 diabetes and LADA, the most important, for both, are
in the histocompatibility [human leukocyte antigen (HLA)]
region of chromosome 6 (14).
HLA alleles associated with type 1 diabetes susceptibility
include HLA DR3, DQB1*0201, and DR4, DQB1*0302,
whereas others are associated with disease protection, e.g.
HLA DR2, DQB1*0602 (16 –19). Children with type 1 diabetes
show an increased prevalence of the heterozygous alleles
HLA DR3, DQB1*0201, and DR4, DQB1*0302, the proportion
of heterozygotes declining with age at diagnosis (19). Chil-
dren with the diabetes-protective HLA DR2, DQB1*0602, are
unlikely to develop diabetes (20), whereas in type 1 diabetes
of adult-onset and LADA, the same alleles carry less pro-
tection (21, 22) (Table 1). Nevertheless, both the latter and
LADA show HLA genetic susceptibility with little or no HLA
genetic protection (19–21).
Strikingly, even adults with non-insulin-requiring diabe-
tes without the diabetes-associated autoantibody to GAD
have an excess of diabetes-associated HLA alleles and are
relatively young and lean (7, 23–25). Age-related genetic
factors also influence the risk of type 1 diabetes. Not only is
the age incidence of type 1 diabetes lower in adults than in
children, the range of incidence across European countries is
also reduced in adults (26). Furthermore, there is a male
excess in incidence that becomes evident during puberty and
is most striking in the age group 25–29 yr (26).
A recent, albeit small, genetic study (8) found similar HLA
susceptibility genes in both type 1 diabetes and LADA. Other
genes have been linked to type 1 diabetes and these genes,
including TNF
␣
, TNF

, IL-10, IL-6 gene polymorphisms, and
IL-18 gene promoter polymorphism, but they have yet to be
studied comprehensively in LADA (27, 28). Other gene poly-
morphisms within the CTLA4, PTPN22, IRS-1, ICOS, and
SUMO4 genes confer a substantial risk to type 1 diabetes with
odds ratios between 1.8 and 2.5 but have not been studied in
LADA (29).
In the light of these observations, it remains possible that
LADA represents one end of a rainbow of autoimmune di-
abetes, which is distinguished from classic type 1 diabetes
only because it is diagnosed in adulthood and presents with
some clinical, anthropometric, and metabolic features more
commonly associated with type 2 diabetes.
LADA in a Spectrum of Nongenetic Influences
Nongenetic factors play a major role in causing type 1
diabetes as shown by studies of populations that have mi-
grated, populations with changing disease incidence, and
twins. We know little of the current incidence of autoimmune
diabetes in adults and LADA. The incidence of a range of
autoimmune diseases, including diabetes, has increased no-
tably over the last three decades (30). The current low se-
lection density and relative stability of HLA gene polymor-
phisms indicates that this increasing incidence cannot be due
to genetic selection pressures and is most likely the result of
nongenetic factors (10, 15).
Unfortunately, population studies are of limited value in
TABLE 1. Genetic, immunological, and metabolic differences between childhood-onset and adult-onset type 1 diabetes and LADA
Children T1DM Adults T1DM LADA
Age at diagnosis Childhood Adulthood Adulthood
Identical twin concordance rate Moderate (e.g. 38%) Very low (e.g. 6%) ?
HLA-DR3/ DR4 Moderate (e.g. 37%) Low (e.g. 13%) Low-moderate (e.g. 22%)
Protective HLA genotype (HLA-DR2) Very low (e.g. 9%) Low (e.g. 15%) Low-moderate (e.g. 22%)
Autoantibodies IAA GAD IA-2 GAD IA-2 GAD IA-2
Plasma insulin Very low Low Low
Note that the children, compared with the others, have a higher identical twin concordance rate, frequency of HLA genetic susceptibility
heterozygosity and insulin autoantibodies, and lower serum insulin levels. HLA DR3/4 is found in about 6% of North American and European
control populations. Data compiled from different sources (6, 11, 17, 19–22). T1DM, Type 1 diabetes mellitus; ?, rate unknown.
TABLE 2. Concordance for type 1 diabetes in identical twins
according to age at clinical onset in the index twin
Young-onset, % (yr) Older-onset, % (yr)
UK/US (Ref. 11) 38 (⬍25) 6 (⬎25)
US (Ref. 12) 44 (⬍15) 13 (⬎15)
Finland (Ref. 13) 50 (⬍10) 23 (⬎10)
Note the substantially lower concordance rates in the older-onset
twins consistent with a marked nongenetically determined effect
causing diabetes in them.
Leslie et al. • Type 1 Diabetes and Latent Autoimmune Diabetes J Clin Endocrinol Metab, May 2006, 91(5):1654 –1659 1655
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identifying the impact of nongenetic factors because it is
difficult to segregate genetic from environmental influences.
However, changes in disease incidence within a genetically
stable population are important when disease incidence rises
rapidly or changes abruptly as in migrants (31, 32). Migrant
studies support a role for environmental factors influencing
disease incidence (32, 33). Type 1 diabetes incidence in Asian
children in families who have migrated to Britain increased
from 3.1 per 100,000 per year in 1978 –1981 to 11.7 per 100,000
per year in 1988–1990, much higher than in their native
Karachi (1 per 100,000 per year) (29, 30). However, Sardinian
migrants moving to continental Italy retained the high inci-
dence of the ancestry region, suggesting that it is the genetic
susceptibility that determines the prevalence of the disease
in response to the environmental factors (34). There are no
comparable migration studies of adults with type 1 diabetes
or of LADA patients. On the other hand, the identical twin
concordance for adult-onset type 1 diabetes is low, implying
that the genetic impact on this form of diabetes is limited,
which in turn suggests a major impact of environmental
factors (10). The declining identical twin concordance rate for
type 1 diabetes with increasing age appears to be a contin-
uum and not a categorical phenomenon, in line with an
age-related spectrum of environmental impact on the etiol-
ogy of autoimmune diabetes. However, there are no twin
studies in LADA, so it is unclear whether this spectrum
extends into that form of autoimmune diabetes.
LADA at One End of a Spectrum of Diabetes-
Associated Immune Responses
At birth, children of mothers with diabetes may have islet
cell autoantibodies (ICAs), insulin autoantibodies (IAAs),
and GAD autoantibodies. But these autoantibodies can also
be found in the maternal serum and are probably placentally
transferred to the child because autoantibody specificities are
similar in mother and cord blood and are not usually de-
tected in the infants of mothers without such autoantibodies
(35–37). Passively acquired maternal autoantibodies disap-
pear after birth as expected but can subsequently be replaced
by the infant’s own autoantibodies.
Diabetes-associated autoantibodies can appear at a later
stage. In one study, three of 58 infants of diabetic mothers
developed IAAs, ICAs, and GAD de novo by 2 yr of age, and
only then were autoantibodies associated with diabetes risk
(35), and in another study,137 children with ICAs from a
prospective Finnish study of 4590 consecutive newborns
with the disease-risk HLA-DQB1, IAAs, and GAD autoan-
tibodies usually appeared in childhood before ICAs, whereas
IA-2 autoantibodies usually appeared later when IAAs are
uncommon (38). In contrast to LADA and adult-onset type
1 diabetes, children often have IAAs at diagnosis and, in
them, IAA is highly predictive of the disease (39). Because
seroconversion continued up to at least age 10 yr of age, it
follows that the induction event with activation of immune
response to produce diabetes-associated autoantibodies is
not confined to early childhood. It remains unclear whether
the age at clinical diagnosis is in part dependent on the age
at which an environmental event activates the immune re-
sponse. If this is the case, then the immune process that leads
to adult-onset type 1 diabetes and LADA would be induced
later in them than in childhood-onset type 1 diabetes.
Taken together these observations suggest that activation
of the diabetes-associated immune process can occur in early
childhood when it is more likely to be associated with IAAs
in those who progress to childhood-onset type 1 diabetes. But
the induction of diabetes-associated autoantibodies is not
confined to early childhood. Currently we have no clear
evidence identifying the age of induction of diabetes-asso-
ciated autoantibodies in those subjects who develop either
adult-onset type 1 diabetes or LADA. However, we know
that these diabetes-associated autoantibodies, when detected
in adult life, are predictive of an ongoing

-cell destructive
process.
In this respect the prevalence of autoantibodies to protein
tyrosine phosphatase isoforms IA-2 and IA-2

/phogrin has
been recently examined in a cohort of adult U.K. Prospective
Diabetes Study patients thought to have type 2 diabetes to
determine whether these autoantibodies predict a require-
ment for insulin therapy (37). In this cohort the presence of
IA-2A was infrequent (about 2%), associated with the HLA-
DR4 haplotype as is the case in classic type 1 diabetes and
highly predictive of insulin therapy (positive predictive
value 60%). The measurement of IA-2

A does not provide
additional information (40).
LADA at One End of a Spectrum of
Metabolic Changes
There is evidence in autoimmune diabetes for a continuum
of metabolic changes, predominantly decreased insulin se-
cretory capacity, but also insensitivity to insulin. These ex-
tend from the severe changes seen in childhood-onset type
1 diabetes to the relatively minor changes initially detected
in LADA.
Some individuals pass through a prediabetic stage of im-
paired glucose tolerance or even non-insulin-requiring dia-
betes before becoming frankly insulin dependent (41). Dia-
betes Prevention Trial of Type 1 Diabetes detected 585
relatives of type 1 diabetic patients who had ICAs plus either
IAAs or low first-phase insulin response to iv glucose (42).
Of these, 427 had normal glucose tolerance, 87 impaired
glucose tolerance, and 61 were diabetic, yet asymptomatic
(39). Of the latter, those with impaired fasting glucose were
significantly older (mean age 21 yr) than those with normal
fasting glucose (mean age 12 yr). These subjects with asymp-
tomatic autoimmune diabetes resemble LADA, but their age
is less than 30 yr precluding the diagnosis. It follows that
some patients with autoimmune diabetes pass through a
phase of altered glucose levels including non-insulin-requir-
ing diabetes before becoming insulin dependent, and the
frequency of this phase, to a degree, is age dependent. It
remains to be determined whether all children with diabetes-
associated autoantibodies will progress to diabetes, let alone
insulin-dependent diabetes. The rate of progression to clin-
ical diabetes is more rapid in patients presenting younger
than 5 yr of age than in those presenting much later (43).
Histological evidence supports this contention: islet

-cells
tend to be absent within 12 months of diagnosis in patients
aged younger than 7 yr but detected for longer periods in
1656 J Clin Endocrinol Metab, May 2006, 91(5):1654 –1659 Leslie et al. • Type 1 Diabetes and Latent Autoimmune Diabetes
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older patients (44). Variability in progression to clinical di-
abetes can even be detected in very young children; for
example, of children identified between 1 and 5 yr of age with
diabetes-associated autoantibodies and subnormal insulin
responses, half of them progress rapidly to diabetes, whereas
the remainder are free from diabetes up to 4 yr later (45).
Other studies have noted such variable progression to type
1 diabetes, which is more rapid in obese than lean children
(46) and in children than adults (47–50). From these obser-
vations it follows that there is a spectrum in the rate of
metabolic decompensation during the prediabetic period in
autoimmune type 1 diabetes, but no data are available, as yet,
in LADA.
Insulin secretory capacity is less in children than adults at
the onset of type 1 diabetes and after diagnosis deteriorates
more rapidly. A study of 235 consecutive cases with newly
diagnosed type 1 diabetes found that those aged younger
than 7 yr had the lowest baseline residual insulin secretion
and required the highest insulin dose for optimal control,
whereas the older the age at diagnosis, the higher was the
basal C-peptide level (51). Patients with LADA also have
reduced fasting and stimulated C-peptide at diagnosis, al-
though the levels of C-peptide are higher than those found
in children and similar to those found in adult-onset type 1
diabetes (8). However, after diagnosis, the C-peptide levels
have been reported to fall more rapidly in childhood-onset
type 1 diabetes than in adult-onset type 1 diabetes and in the
latter more rapidly than in LADA (52–55). Furthermore, per-
sistent C-peptide secretion, implying less aggressive disease,
is detected in more adults than adolescents after diagnosis of
type 1 diabetes and in more adolescents than prepubertal
children with diabetes (52–54). Other studies report a quite
rapid loss of C-peptide even in LADA, which argues against
a chronic destructive process in that condition (6, 55, 56). In
summary, there is a continuous spectrum of loss of insulin
secretory capacity, the severity of which can be age related,
being more severe in children than adults with type 1 dia-
betes and more severe in the latter than in LADA subjects,
although some patients with LADA may show a rapid loss
of insulin secretory capacity.
The metabolic decompensation that leads to frank diabetes
could result from either increased linear growth, which has
been linked to diabetes risk, or increased childhood obesity,
which has been correlated with age at presentation (10, 46).
People with LADA may well have more severe loss of insulin
sensitivity than in childhood-onset type 1 diabetes, but there
are only two small studies (57, 58) considering insulin sen-
sitivity in LADA, and both used the homeostasis model of
assessment, whereas no studies have used the gold standard
euglycemic hyperinsulinemic clamp. Certainly in LADA the
frequency of the metabolic syndrome, usually associated
with insulin resistance, although less prevalent than in type
2 diabetic patients of similar age, is more prevalent than in
the general population (9). In a recent report, the metabolic
syndrome, which is found in approximately 22% of the North
American population was identified in 74% of those with
LADA but in significantly more subjects with type 2 diabetes
(84%) (9).
It is likely, therefore, that within autoimmune diabetes,
including both type 1 diabetes and LADA, there is an age-
related spectrum of decreasing insulin secretory capacity and
increasing insulin insensitivity associated with the metabolic
syndrome. The distinction between LADA and adult-onset
classical type 1 diabetes is a matter of debate. It is possible
that the distinction between the two is one of degree, with the
classical type 1 diabetes being at one end of the spectrum and
LADA, when it remains insulin independent, being at the
other end.
A Spectrum of Clinical Management in LADA
Type 1 diabetes progresses to insulin dependence usually
within 2 yr of the clinical diagnosis as noted in the preinsulin
era. Before 2 yr some patients may have a partial or complete
remission when insulin therapy is not required (59). Of
LADA patients, in one study (7), 94% required insulin treat-
ment by 6 yr as compared with only 14% in those initially
non-insulin-requiring diabetes patients without either GAD
autoantibodies or ICAs. Progression to insulin dependence
in LADA patients was more rapid in those aged younger
than 45 yr than in older cases (7). It follows that patients with
autoimmune diabetes, including both type 1 diabetes and
LADA, are at high risk of progression to insulin dependence,
but that risk declines with age at diagnosis.
It is well established that insulin is the treatment of choice
for type 1 diabetes, but there is no established management
strategy for patients diagnosed with LADA (60– 65). The
European Union, therefore, funded a major initiative
(ACTION-LADA) to study the characteristics of LADA and
report on how to treat it. In considering how to treat LADA,
some important questions arise as to our broad management
of autoimmune diabetes. Because the predominant defect in
autoimmune diabetes is loss of insulin secretion, should we
treat the disease with insulin irrespective of the level of
dependency on insulin? Autoantibody positive, initially non-
insulin-requiring, diabetic patients initially treated with sul-
fonylureas have been found to require insulin earlier than
autoantibody-negative patients, but sulfonylureas did not
have an impact on the need for insulin treatment or the time
to progression to insulin therapy (41).
Metformin is routinely offered to patients with non-insu-
lin-requiring diabetes, but its specific role in LADA is un-
clear, and the drug may be contraindicated in those with
LADA because there is a theoretical risk of severe metabolic
disturbance in individuals who progress to insulin depen-
dency while on it. Intriguingly, however, there is limited
evidence that metformin could be of value, even in patients
with type 1 diabetes. For example, in one study, adolescent
type 1 insulin-dependent diabetes patients given metformin
subsequently showed a significantly lower hemoglobin A1c
and reduced insulin requirements, compared with those not
taking metformin (62).
Thiazoledinediones also might theoretically be of value
because they not only improve insulin sensitivity but also
have an antiinflammatory effect and protect nonobese dia-
betic mice, a well-established model of autoimmune diabe-
tes, from developing diabetes (63). In a small study of LADA
patients in China (64), there was a significant improvement
in C-peptide but not hemoglobin A1c in patients receiving
rosiglitazone plus insulin, compared with insulin alone.
Leslie et al. • Type 1 Diabetes and Latent Autoimmune Diabetes J Clin Endocrinol Metab, May 2006, 91(5):1654 –1659 1657
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Because the primary defect in autoimmune diabetes is loss
of insulin secretion, treatment should aim to restore islet
insulin secretion. Therapy to prevent progression toward
insulin dependency could include insulin or immunomodu-
lation, given the inflammatory nature of the disease process
thought to cause insulin secretory cell destruction. The op-
timal insulin regimen is unclear; given the broad loss of
insulin secretory capacity, it might be argued that the early
introduction of a long-acting insulin could be beneficial. Al-
ternatively, the loss of rapid insulin release in LADA patients
suggests that replacement with a fast-acting insulin would be
more valuable.
One study in Japan of patients with LADA compared early
treatment with insulin given as multiple injections with sul-
fonylureas (61). Although of limited power, this study did
show a statistically significant persistence of C-peptide in the
insulin-treated group as compared with the sulfonylurea
group with the proviso that the insulin-treated group had
preserved insulin secretory capacity and a high titer of GAD
autoantibodies at the start of the study (61). An alternative
interpretation of this study is that sulfonylureas are disad-
vantageous, in support of which sulfonylureas could theo-
retically promote apoptosis, apoptosis being one mechanism
whereby insulin-secreting cells could be destroyed in auto-
immune diabetes.
A pilot phase 2 trial in LADA patients (65) found that a
tolerance induction plan using alum-formulated whole GAD
(Diamyd) had a significant effect on the C-peptide response
to a mixed meal consistent with modulation of the aggressive
process. Another phase 2 trial in LADA patients using the
peptide analog of heat shock protein 60 (Diapep 277) has
been completed after initial positive results in protecting
residual

-cell function in adult-onset type 1 diabetes pa-
tients (66) and in experimental models of the disease (67).
These immunomodulatory studies, although small and pre-
liminary, pioneer a novel approach toward the maintenance
of islet cell function, itself a new field in the management of
autoimmune diabetes.
In conclusion, LADA, whether viewed genetically, immu-
nologically, metabolically, or clinically, occupies one end of
a rainbow of features associated with autoimmune diabetes.
The management and prevention of LADA need to be in-
vestigated to define the best strategy for treating this most
prevalent form of autoimmune diabetes.
Acknowledgments
We thank all our collaborators, in particular Drs. Mohammed Hawa,
Huriya Beyan, Chiara Guglielmi, Marta Vadacca, Sinead Brophy, and
Mark Airey, for their contribution to the work in our laboratories and
in the field.
Received July 21, 2005. Accepted February 7, 2006.
Address all correspondence and requests for reprints to: Professor
David Leslie, Department of Diabetes, St. Bartholomew’s Hospital, West
Smithfield, London EC1A 7BE, United Kingdom. E-mail: r.d.g.leslie@
qmul.ac.uk.
The work in London, Swansea, and Rome was supported by grants
from the Juvenile Diabetes Research Foundation, Develogen, Diabetes
UK, Diabetes Twin Research Trust, and the European Union.
The authors have nothing to declare.
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