Articles
From: Victoria (anonymous@obgyn.net)
Sat, 30 Mar 2002 13:38:22 -0500
--
Victoria
> From the Arbor Clinical News:
>
> Study one: Exercise and diet prevents insulin resistance
> developing to diabetes
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> -----
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> Diet and exercise modification can significantly reduce the likelihood of
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> developing type 2 diabetes in those at high risk, and is more effective in
> doing so than the drug metformin. These results from the US-based Diabetes
> Prevention Program Research Group were published in last month's New
> England Journal of Medicine.
>
> Subjects: 3,234 subjects who did not have diabetes, but who did have
> elevated glucose both on fasting and after glucose loading. Their mean body
> mass index was 34.0 and their average age was 51 years at outset.
>
> Method: Randomised controlled trial in which subjects were assigned either
> to an intensive lifestyle modification program, metformin (850 mg twice
> daily), or placebo.
>
> Metformin and placebo groups were given basic lifestyle advice, including
> an annual health counselling session.
>
> The intensive lifestyle intervention group received a 16 lesson curriculum
> on diet, exercise and behaviour modification which aimed to achieve a 7%
> weight loss and 150 minutes of moderate intensity exercise weekly. The
> curriculum was taught one-on-one over the first 6 months after enrollment,
> and followed up with further monthly individual sessions and group sessions.
>
> Results: The average length of follow up was 2.8 years, and 92.5% of
> participants still alive at this time had attended a scheduled visit within
> the preceding 5 months.
>
> Overall, 38% had a weight loss of at least 7% at the most recent visit,
> and 58% were exercising 150 minutes per week (based on log diaries).
>
> The impact of the interventions is shown in the Table.
>
> Table 1: Incidence of diabetes developing during the course of the
> intervention
>
> Lifestyle Metformin Placebo
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> ----
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> 4.8% 7.8% 11.0%
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>
> All comparisons are p<0.05
>
> The intensive lifestyle intervention was more effective in preventing
> diabetes in the older patients, those with less glucose intolerance and
> lower BMI. Metformin was significantly more effective in the more obese
> patients.
>
> Reference: N Engl J Med 2002;346:393-403
>
> Study two: complex carbohydrates better
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> Replacing fat intake with complex carbohydrate for 6 months in adults with
> -------------------------------------------------------------
> metabolic syndrome results in modest improvements in weight, according to
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> results from a new English study.
>
> Subjects: 46 subjects with at least 3 features of the metabolic syndrome
> (for details of these diagnostic criteria, see our last issue #120).
>
> Method: Random assignment to one of three protocols: control, low fat diet
> emphasising complex carbohydrates, or low fat diet where fat substitution
> was predominantly with simple carbohydrates. 60% of the diet was supplied
> free through a grocery store, but no energy restriction was enforced in the
> diets.
>
> Results: 85% of the subjects completed the trial. There was a significant
> loss in body weight in the complex carbohydrate diet subjects only (-4.25
> kg, p<0.05).
>
> Whilst total cholesterol decreased in all three groups, this was not due
> to any significant drop in LDL cholesterol. Instead there was a fall in HDL
> cholesterol in all three groups. Serum triglyceride levels were
> significantly higher after the simple CHO diet than with either of the
> other two diets (p<0.05)
>
> Reference: Am J Clin Nutr 2002;75:11-20. #11756055]
>
> Study three: Long term benefits decrease
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> Many of the benefits of low fat diet in adults with metabolic syndrome
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> diminish over time, except in the most compliant patients, according to
> -------------------------------------------------------------
> recent research from New Zealand.
>
> Subjects: 136 adults with glucose intolerance.
>
> Method: This was a 5 year follow up to an original intervention trial, in
> which the subjects had been randomised to either a reduced fat diet
> (supported by monthly small group education sessions) or control diet for
> one year.
>
> Results: 76% of the participants were included in the final 5 year follow
> up. Although both weight and glucose tolerance had significantly improved
> in the intervention group at the end of the first year, these improvements
> were not present at 5 years. See Table 3.
>
> However, the more compliant half of the intervention subjects did have
> better glucose tolerance at the 5 year mark (p<0.05 for both fasting and 2
> hour glucose values).
>
> Table 3: Weight loss over 5 years on low fat diet (compared with control)
>
> Year 1 -3.3 kg
> Year 2 -3.2 kg
> Year 3 -1.6 kg
> Year 5 +1.1 kg
>
> Reference: Diabetes Care 2001;24:619-24
>
> COMMENTS
> These three studies illustrate nicely both the potential and the
> frustration of treating people with metabolic syndrome.
>
> There is potential to use approaches that deal directly with the glucose
> intolerance side of metabolic syndrome. For example, by using oral
> hypolgycaemic drugs (such as metformin) or by following diets with a low
> glycaemic index or increased amount of monounsaturated fatty acids etc.
> Exercise itself has a direct beneficial effect on glucose tolerance.
>
> However, whatever the potential of these approaches, the successful
> management of metabolic syndrome will always include reducing central
> adiposity.
>
> The first study from the Diabetes Prevention Program Research Group
> illustrates how much benefit can be obtained from lifestyle change
> involving weight loss and exercise. Despite only modest compliance, the
> reduction in diabetes incidence obtained was impressive.
>
> The study also showed that lifestyle intervention was substantially more
> effective in this respect than metformin, although the results suggest that
> metformin may have a particular role in preventing diabetes in more obese
> patients.
>
> But we must not overlook the fact that considerable effort was required to
> achieve this lifestyle intervention. Few primary care practices will find
> it easy to replicate the amount of time and energy that each patient in
> this lifestyle group received. The relative benefits of metformin vs
> lifestyle need to be considered in that light.
>
> The second and third trials used less intense interventions. The six month
> results from the second study were modest, but demonstrate that the type of
> carbohydrate used in dietary modification is important. A higher complex
> carbohydrate diet is also likely to have a lower glycaemic index.
>
> Both dietary intervention groups in this study had a fall in HDL
> cholesterol - a known effect of substituting fat with CHO. We need to know
> a more about what is the best way to go about dietary change in patients
> with metabolic syndrome in relation to their lipid pattern. There may, for
> example, be a role for increasing the intake of medium chain fatty
> acids (ref. 1).
>
> Ultimately, however, it is the long term outcomes that count - 5-10 years
> and beyond. We do not have many studies of this nature in patients with
> metabolic syndrome, and hence the New Zealand study adds valuable
> experience. As we might expect, it showed that the benefits of lifestyle
> intervention are hard to maintain. On the other hand, it did also show that
> more motivated patients can achieve better outcomes - in this case
> maintaining their improved glucose tolerance over 5 years.
>
> There are many questions still to be resolved about preventive and
> treatment strategies for metabolic syndrome. For example, is it worth
> actively screening our patients for insulin resistance before they have
> significant or any overweight, hyperlipidaemia or hypertension and if so
> from what age? Are our treatment efforts better concentrated on those with
> multiple risk factors or on all overweight patients (on the assumption
> that, if they do not already have insulin resistance, most will eventually
> develop it)?
>
> We do know that adiposity and insulin resistance are associated from quite
> early in life, and that childhood adiposity is a reasonable predictor of
> the risk of developing metabolic syndrome in adulthood (ref. 2). The same
> may not however be true of insulin resistance in childhood (ref. 3).
>
> What it means to the clinician
> Our growing understanding about metabolic syndrome only reinforces the
> importance for us as clinicians to identify our overweight patients at an
> early stage and encourage them to lose weight and undertake more physical
> activity. It does seem that there may be value in also monitoring glucose
> tolerance, and that therapies specifically targetted at insulin resistance
> (such as metformin) will have a role. It remains to be seen exactly what
> role.
>
> References:
> 1. J Nutr 2002;132:329-32
>
> 2. Prev Cardiol 2001;4:116-121
>
> 3. J Clin Endocrinol Metab 2002;87:71-6
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