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ABSTRACT
The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality
worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A
growing body of evidence suggests that although the risk of developing complications is greater with
glucose levels beyond the established threshold for diagnosis e increasing in parallel with rising hyperglycemiaindividuals with glucose levels in the prediabetic range are already at increased risk. Early
intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to
minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these
challenges, the benets of early interventionwith emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetesand the existing evidence-based
guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type
2 diabetes stages.
2013 Published by Elsevier Inc. The American Journal of Medicine (2013) 126, S2-S9
KEYWORDS: Complications; Diabetes prevention trials; Diagnosis; Early intervention; Prediabetes
Funding: The publication of this article was funded by Novo Nordisk Inc.
Conict of Interest: REP has received Research/Clinical Trial Support
from GlaxoSmithKline, Lilly, Mannkind, Merck, Novartis, Novo Nordisk,
Pzer, Roche, Sano and Takeda; and has attended Advisory Panel/acted as
a Consultant or Speaker for AstraZeneca/Bristol-Myers Squibb, Eisai,
GlaxoSmithKline, Lexicon, Mannkind, Merck, Novo Nordisk, Novartis,
Roche, Sano and Takeda. As of June 2011, all honoraria are directed to a
nonprot foundation.
Authorship: Writing support was provided by Watermeadow Medical.
The author takes responsibility for the content of this manuscript.
Requests for reprints should be addressed to Richard E. Pratley, MD,
Florida Hospital Diabetes Institute, 2415 North Orange Avenue, Orlando,
FL 32804.
E-mail address: richard.pratley@hosp.org
0002-9343/$ -see front matter 2013 Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.amjmed.2013.06.007
Pratley
Early Treatment
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Although microvascular complications increase morbidity and lead to premature mortality, the major cause of
death in individuals with diabetes is CVD, accounting for
approximately 65% of all diabetes-related deaths.24 For
example, transient ischemic attacks are 2-6 times more
common in patients with type 2 diabetes,24 while the risk of
developing heart failure is a startling 2- to 8-fold higher.25
Figure
S4
in the US between 2007 and 2010, and a very small minority (18.8%) achieved all 3 targets.37
DIAGNOSING DIABETES
Diagnosis and Classication Criteria
The World Health Organization (WHO) and the International Diabetes Federation (IDF) have dened criteria for the
diagnosis of diabetes, with cutoff limits based on levels of
Pratley
Table 1
Early Treatment
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Criteria for Testing for Type 2 Diabetes or Assessing the Risk of Future Type 2 Diabetes in Adults*
1. Testing should be considered in all adults who are overweight (BMI 25 kg/m2) and have additional risk factors:
Physical inactivity
First-degree relative with diabetes
High-risk race/ethnicity (eg, African American, Latino, Native American, Asian American, Pacic Islander)
Women who delivered a baby weighing >9 lb or were diagnosed with gestational diabetes
Hypertension (140/90 mm Hg or on therapy for hypertension
High-density lipoprotein cholesterol level <35 mg/dL (0.90 mmol/L) or triglyceride level >250 mg/dL (2.82 mmol/L)
Women with polycystic ovarian syndrome (PCOS)
A1c >5.7%, impaired glucose tolerance, or impaired fasting glucose on previous testing
Other clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis nigricans)
History of cardiovascular disease
2. In the absence of the above criteria, testing for diabetes should begin at age 45 years
3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on
initial results and risk status.
* 2011 American Diabetes Association, reproduced with permission from Diabetes Care 2011; 34(Suppl 1):S11-S61.38
At-risk body mass index (BMI) may be lower in ethnic groups.
S6
Table 2
Criteria
Overweight (BMI >85th percentile for age and sex, weight for height >85th percentile, or weight >120% of ideal for height
Plus any 2 of the following risk factors
B Family history of type 2 diabetes in rst- or second-degree relative
B Race/ethnicity (Native American, African American, Latino, Asian American, Pacic Islander)
B Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia,
polycystic ovarian syndrome [PCOS], or small-for-gestational-age birth weight)
B Maternal history of diabetes or gestational diabetes during the childs gestation
B Age of initiation: age 10 years or at onset of puberty, if puberty occurs at a younger age
Frequency: every 3 years
* 2011 American Diabetes Association, reproduced with permission from Diabetes Care 2011; 34(Suppl 1):S11-S61.38
Metformin
Unless contraindicated or not tolerated, metformin is
generally the recommended initial pharmacotherapy in
combination with lifestyle changes, as it has been shown to
reduce glycemia effectively (A1c reductions of approximately 1.5% can be achieved with metformin monotherapy)
with a low risk of hypoglycemia and no weight gain or
modest weight loss. In addition, it is generally well tolerated, with gastrointestinal side effects being most common,
affecting up to 63% of patients on initiation of treatment.74,75 For this reason, metformin should be titrated
slowly; the ADA/European Association for the Study of
Diabetes (EASD) consensus algorithm recommends beginning with low-dose metformin (500 mg) once or twice a day
with meals or 850 mg once a day, increasing the dose after
5-7 days if gastrointestinal side effects have not occurred.
The maximum effective dose can be up to 1000 mg
twice a day.74
Metformin is contraindicated in patients with renal disease or renal dysfunction (serum creatinine clearance 1.5
mg/dL in males or 1.4 mg/dL in females) as it may increase the risk of lactic acidosis. Other contraindications
include hypersensitivity to the active ingredient (metformin
hydrochloride) and conditions such as acute or chronic
metabolic acidosis, including diabetic ketoacidosis with or
without coma.76
Pratley
Early Treatment
CONCLUSION
Type 2 diabetes has reached epidemic proportions and is
one of the leading causes of premature morbidity and
mortality worldwide. Evidence suggests that the burden of
type 2 diabetes can be lowered substantially with intensive,
multifactorial intervention to target hyperglycemia, the
hallmark of the disease, as well as hypertension and
hyperlipidemia, which often coexist with type 2 diabetes. In
addition, the burden of the disease could be further reduced
with early intervention to address prediabetes, as mounting
evidence suggests that this approach could prevent, or at
least delay, progression to overt diabetes. However, most
people do not benet from this, as prediabetes is largely
underdiagnosed.
The diagnosis of overt type 2 diabetes is not without
challenges. Although clear guidelines exist on the criteria
for diagnosing and classifying diabetes, a large number of
patients are undiagnosed, as the disease can remain
asymptomatic for long periods of time. Therefore, screening
patients with increased risk for type 2 diabetes may help to
reduce the burden of the disease.
Once type 2 diabetes is diagnosed, it is of utmost
importance that patients receive optimum standard of care to
avoid complications. Although they vary by location, evidence-based country-specic guidelines provide recommendations on how to achieve optimum standard of care in
a safe and effective manner, choosing the most appropriate
intervention from the available pharmacotherapy.
ACKNOWLEDGMENT
The author takes full responsibility for this paper but is
grateful to Angela Pozo Ramajo, PhD, of Watermeadow
Medical (supported by Novo Nordisk Inc.) for writing
assistance.
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