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What would the recommended therapy be for an obese young
adult with fasting plasma glucose of 122mg/dL who has gone 90 days of
intensive life style change counseling?
1. Continue with Lifestyle Change counseling
2. Add Metformin
3. Add Acarbose
4. Add Actos
There have been several developments since the last time this question
was addressed, but we still don't have a clear answer. For one thing,
a new term has been introduced. The American Diabetes Association (ADA)
and the National Institute of Diabetes, Digestive and Kidney disease
(NIDDK) held a news conference this past spring. Representatives of
these institutions introduced the term prediabetes, designed to describe
the cumbersome terms "impaired glucose tolerance" (IGT) and
"impaired fasting glucose" (IFG). These terms are descriptive
and helpful, but are confusing to patients and healthcare professionals.
Prediabetes is defined as a fasting plasma glucose >/= 110 and <
125 mg/dL, or a postchallenge plasma glucose >/= 140 and < 200
mg/dL.
In addition, there have been several additional articles published over
the last year. The Diabetes Prevention Program (DPP) was a landmark
study involving 3234 patients with IGT followed for an average of 2.8
years. Some patients in the DPP were randomized to lifestyle interventions.
The lifestyle intervention consisted of a minimum of 150 minutes of
physical activity per week, and resulted in a 7% reduction in weight.
The risk reduction in conversion of IGT to diabetes from lifestyle was
58%. The DPP also included a group that was assigned to metformin 850
mg twice daily. The risk reduction in progression to diabetes was significant
-- 31% -- but not as dramatic as the lifestyle-intervention group. This
led the ADA to issue a Position Statement, stating that lifestyle intervention
is both significantly more effective and better studied than are medications.
With the lack of available data to support using drugs, the ADA has
concluded that "there is insufficient evidence to support the use
of drug therapy as a substitute for, or in addition to, lifestyle modification
to prevent diabetes."
Two additional studies have looked at diabetes prevention using medication.
The Study to Prevent Noninsulin-Dependent Diabetes Mellitus, or STOP-NIDDM,
was a multinational, randomized, controlled trial. A total of 1429 patients
with IGT were randomized to either 100 mg of acarbose thrice daily or
to placebo, and were followed for a mean of 3.3 years. Forty-two percent
of placebo-treated patients developed diabetes, compared with 32% of
patients treated with acarbose, representing a 25% reduction. When patients
who discontinued treatment early were dropped from the analysis, acarbose-treated
patients experienced a 91% reduction in acute myocardial infarction,
and were 49% less likely to develop any cardiovascular event. [3]
Another study pertaining to diabetes prevention was published in September
2002. The Troglitazone in Prevention of Diabetes study, or TRIPOD, followed
236 high-risk Hispanic women from Los Angeles, California, who had gestational
diabetes within the last 4 years. They were randomized to troglitazone
400 mg/day or placebo, and were followed for a median of 30 months.
The annual diabetes incidence rates declined from 12.1 % in the placebo
group to 5.4% in the troglitazone group, representing a 55.3% reduction
in new diabetes. A subset of women who had not yet developed diabetes
returned for testing 8 months after stopping the trial, and only 1 woman
who had been in the troglitazone arm went on to develop diabetes. This
suggests that the drug altered the underlying metabolic changes that
lead to diabetes, and these changes persisted even after the drug was
stopped.
In summary, there are now 3 published randomized trials that have examined
the use of medications in the prevention of diabetes. It is difficult
to compare and extrapolate the results because the trials were significantly
dissimilar and involved different populations. Some observations about
the profile of the patients can be made, however. In the DPP, significant
efficacy from metformin in preventing diabetes was seen in subjects
who were younger, heavier men with a higher baseline fasting glucose.
In the STOP-NIDDM, significant efficacy from acarbose in preventing
diabetes was seen in older, leaner, normotensive women with a lower
baseline fasting insulin level. In the TRIPOD study, significant efficacy
from troglitazone in preventing diabetes was seen in women who had significant
insulin resistance and hyperinsulinemia at baseline.
To return to the question, the best choice of action for this patient
remains the same. Intensive lifestyle efforts including diet, exercise,
behavior modification, weight loss, and cardiac risk reduction are still
the recommended methods for preventing diabetes. A referral to a comprehensive,
multidisciplinary weight management center may provide assistance beyond
what can be offered in a private practice setting. From the studies
described above, however, a clinician may wish to consider including
a medication for selected patients who seem to be losing the battle.
In this case, the patient may already have converted to type 2 diabetes,
and a medication in addition to lifestyle changes would then be considered.
From the patient profiles noted, a medication such as metformin would
seem to be a reasonable choice.
References
1. Diabetes Prevention Program Research Group. Reduction in the incidence
of type 2 diabetes with lifestyle intervention or metformin. N Engl
J Med. 2002;346:393-403.
2. American Diabetes Association and National Institute of Diabetes,
Digestive and Kidney Diseases. Position Statement. The prevention or
delay of type 2 diabetes. Diabetes Care. 2002;25:742-749.
3. Chiasson JL, Josse RG, Gomis R, et al. STOP-NIDDM Trail Research
Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM
randomised trial. Lancet. 2002;359:2072-2077.
4. Buchanan TA, Xiang AH, Peters RK et al. Preservation of pancreatic
beta-cell function and prevention of type 2 diabetes by pharmacological
treatment of insulin resistance in high-risk Hispanic women. Diabetes.
2002;51:2796-2803.
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