EDITORIAL
Management of prediabetes: setting the stage
The public health and economic consequences of the
ever-growing epidemic of type 2 diabetes mellitus
(T2DM) have refocused attention on the need to intervene
in the prediabetes state to prevent progression to overt
T2DM and its complications. In considering preventive
strategies, many issues have to be confronted, including
how, when and in whom to intervene.
Who should be screened for glucose dysregulation, and
which of the different definitions of impaired fasting glu-
cose (IFG) and/or impaired glucose tolerance (IGT) are bet-
ter predictors of T2DM and cardiovascular disease? Can
populations at the highest risk within the continuum of
glucose dysregulation be identified to be effectively targeted
for therapy? Lifestyle intervention consisting of diet and
exercise has proven effective in reducing risk of progression
to T2DM in subjects with IGT, but it is difficult to maintain
lifestyle modification. Nonetheless, education regarding
lifestyle should be a cornerstone of preventive efforts.
Pharmacologic intervention has also been effective in
reducing risk of progression to T2DM, but there are criti-
cal issues regarding selection of the right target popula-
tions and the proper drug therapies. It remains unclear
whether antidiabetic agents (e.g. metformin or thiazolidi-
nediones) can exert sustained disease-modifying effects
on the underlying defects causing glucose dysregulation
or simply control glucose levels as a direct effect for vari-
able periods of time. In addition, to date, we have very
little information on whether intervention during the pre-
diabetes state reduces the risk of adverse cardiovascular
outcomes associated with T2DM.
A symposium entitled ‘Islet Enhancement through
DPP-4 Inhibition as a Treatment Strategy in Prediabetes’
was held at the recent second International Congress
on ‘Prediabetes’ and the Metabolic Syndrome in Barce-
lona, Spain. This supplement reports the contents of
that symposium.
Correspondence:
Julio Rosenstock, MD, Dallas Diabetes and Endocrine Center at Medical City, 7777 Forest Lane C-685, Dallas, TX, 75230, USA.
E-mail:
juliorosenstock@dallasdiabetes.com
Conflict of interest statement:
J. R. has served on advisory boards and received honoraria or consulting fees from Pfizer, Sanofi-Aventis, Novo Nordisk, Glaxo-
SmithKline, Takeda, Centocor, Johnson & Johnson and Amylin; and has received grant support from Merck, Pfizer, Sanofi-Aventis,
Novo Nordisk, Eli Lilly, GlaxoSmithKline, Takeda, Novartis, AstraZeneca, Amylin, Sankyo and MannKind.
# 2007 The Author
Journal Compilation # 2007 Blackwell Publishing Ltd
doi: 10.1111/j.1463-1326.2007.00767.
d In the opening article, I reflect on some of the issues
and the current thinking regarding prevention of T2DM
and provide highlights on some of the data from pre-
vention trials, putting in perspective the recent Ameri-
can Diabetes Association consensus statement on IFG/
IGT and its implications for treatment.
d George Alberti provides an insightful discussion on
the definition of ‘prediabetes’ and the measures that
need to be used in screening for high risk of develop-
ing T2DM. He emphasizes two principles for action:
first, screening by fasting blood glucose measurement
alone is insufficient to identify individuals at highest
risk for adverse consequences of T2DM and second,
screening among high-risk individuals would require
use of oral glucose tolerance testing to demonstrate
IGT because IGT is associated with greater risk of pro-
gression than is IFG.
d While discussing potential pharmacologic interven-
tion in prediabetes, Stefano Del Prato stresses that
educational and more creative societal initiatives that
alter the lifestyle trends driving the growth of the dia-
betes epidemic are critical to the success of reversing
current disease trends. He maintains that careful risk–
benefit analysis is necessary for preventive strategies
involving drug therapy, as they would entail exposure
of asymptomatic individuals at variable risk of T2DM
to potential drug adverse effects.
d Based on a symposium presentation by Daniel
Drucker on the physiology of the incretin system and
the associated derangements in T2DM, Carolyn F Dea-
con reviews the development and characteristics of
the new incretin-based antidiabetic agents, including
the oral dipeptidyl peptidase-4 (DPP-4) inhibitors.
These agents enhance islet b-cell and a-cell function,
resulting in improved glucose-dependent insulin
secretion and reduced inappropriate glucagon
Diabetes, Obesity and Metabolism, 9 (Suppl. 1), 2007, 1–2 j 1
E j Editorial
secretion, with demonstrated improvements in gly-
caemic control in multiple clinical trials. In addition,
DPP-4 inhibitors have been found to increase b-cell
neogenesis and mass in preclinical studies. These
findings, together with a low risk for hypoglycaemia,
a weight-neutral effect, and – so far – a relatively
benign tolerability profile, make these oral agents
intriguing candidates for reversing glucose dysregula-
tion in prediabetes.
d Finally, Gaia Panina reviews the pharmacody-
namics of the DPP-4 inhibitor vildagliptin and
2 j Diabetes, Obesity and Metabolism, 9 (Suppl. 1), 2007, 1–2
Editorial
the extensive clinical research programme that
demonstrated its efficacy in monotherapy or as
add-on treatment in T2DM. She also reviews some
preliminary findings in the setting of IGT that may
provide the basis for future long-term trials in pre-
diabetes.
Julio Rosenstock
Dallas Diabetes and Endocrine Center at Medical City,
Dallas, TX, USA
# 2007 The Author
Journal Compilation # 2007 Blackwell Publishing Ltd