DM Full Guideline (2010) - VA/DoD Clinical Practice Guidelines Home

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DISCUSSION
VA/DoD Clinical Practice Guideline
for the Management of Diabetes Mellitus
There is evidence in patients with diabetes that both duration and severity of hyperglycemia increase risk for
microvascular and perhaps macrovascular complications (UKPDS 1998, DCCT, 1993). Up to 20-50% of patients
with newly diagnosed with DM have microvascular disease (UKPDS, 1998). Treatment of hyperglycemia reduces
the increased risk of complications (DCCT, 1993; UKPDS-33, DCCT/EDIC). However, treatment of pre-diabetes,
which may delay the diagnosis of diabetes, has not been shown to affect microvascular or macrovascular disease.
The diagnosis of pre-diabetes and DM are, by convention, dichotomous but risks associated with hyperglycemia are
continuous.
There is evidence from the DPP (Knowler et al., 2002) that persons with pre-diabetes who participate in intensive
lifestyle modification including regular aerobic exercise and calorie-restricted diet and achieve a sustained weight
loss, develop DM at a lower rate than untreated individuals. In addition, a meta-analysis (Yamaoka & Tango, 2005)
showed that in patients with pre-diabetes, education in lifestyle modifications reduces progression to diabetes by
50%. Collectively, these observations suggest that treatment of pre-diabetes may prevent the complications of
diabetes.
Two high quality RCTs addressed the impact of weight loss/exercise on the development of type 2 DM in adults
with IGT (Swinburn et al., 2001; Tuomilehto et al., 2001). Both studies concluded that diet and/or exercise, as
compared to placebo, delayed the onset of diabetes in patients with glucose intolerance. In addition, Knowler et al.
(2002) found that diet and exercise were significantly more effective than metformin in prevention of diabetes in
glucose intolerant patients.
Two lower quality RCTs also showed that diet and/or exercise will delay the onset of diabetes in glucose-impaired
individuals (Knowler et al., 2002; Pan et al., 1997).
While lifestyle modifications are preferred, many patients will either not respond or have only initial success. In
these patients, the use of pharmacologic agents could be considered. A series of agents have been studied – alphaglucosidase
inhibitors, metformin, thiazolidinediones; and in hypertensive patients, angiotensin converting enzyme
inhibitors and angiotensin receptor blockers. Each has been shown to delay progression from pre-diabetes to
diabetes. There are no data that suggest that the selection of one agent is preferred over another. None have been
shown to reduce long-term complications of diabetes and none have FDA indications for this use. While the
thiazolidinediones have been shown to delay diabetes, they are not recommended because of concerns over their
long-term safety data and side effects associated with their use.
EVIDENCE
Recommendation Sources LE QE SR
1 Weight loss and exercise counseling Yamaoka and Tango, 2005 I Good A
of patients with FPG >100.
2 Diet and exercise leading to weight
loss may slow progression to
diabetes.
Knowler et al., 2002
Tuomilehto et al., 2001
Pan et al., 1997
Gillies et al., 2007
I Good A
3 Weight loss for patients with a BMI
>25 or those with other risk
factors for diabetes
4 Lifestyle modification for patients
with other risk factors.
5 Pharmacologic therapy delays
progression to the diagnosis of
diabetes
Knowler et al., 2002
Swinburn et al., 2001
Tuomilehto et al., 2001
Pan et al., 1997
Field et al., 2001
Manson et al., 1992
Chiasson et al., 2006
Gillespie et al., 2005
Scheen et al., 2004
Padwal et al., 2005
Van de Laar et al., 2006
Salpeter et al., 2008
LE-Level of Evidence; QE = Quality of Evidence; SR = Strength of Recommendation (see Appendix A)
I Good A
II-2 Fair B
I Good A
Module S: Screening for Diabetes Page 38