The “Legacy Effect” in Diabetes – The Long-Term Benefits of Short-Term, Tight Glucose Management
By Matthew GarzaFrida Velcani
By Matthew Garza and Frida Velcani
A summary of the landmark trials that show that careful blood glucose management can lower the risk of long-term health complications in people with type 1 or type 2 diabetes
The “legacy effect” describes the long-term health benefits that result from intensive (or tight) blood glucose management in diabetes care compared to standard glucose control. In this article, we share some of the key findings from landmark studies that explore the legacy effect in people with type 1 and type 2 diabetes.
Note: While none of these trials used continuous glucose monitoring (CGM), we believe there is huge potential for CGM metrics like time in range to help people recently diagnosed with diabetes manage their blood glucose levels (in a way that A1C may not). Learn more about how people with diabetes can benefit from time in range.
The legacy effect in people with type 1 diabetes
The Diabetes Control and Complications Trial (DCCT) evaluated the effects of tighter glucose management on people with type 1 diabetes. They were randomized to receive either intensive, tight glucose control (dosages of insulin adjusted by self-monitoring of blood glucose, SMBG) or conventional glucose control, usually with two injections per day that were not frequently adjusted based on SMBG. Participants in the intensive group either used an insulin pump or administered three injections of insulin per day. Glucose control, macrovascular complications, and microvascular complications were all monitored and recorded.
The DCCT was stopped early for ethical reasons, because its findings were so striking in reduced complications. When the DCCT ended, participants were invited to take part in an observational study called EDIC, which has been ongoing for more than 20 years. EDIC has tracked the long-term effects of the treatments initially assigned to participants in DCCT. While blood sugar has been about the same in both groups during EDIC, the results showed:
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People in the intensive group (who had an average A1C of 7.2% during DCCT (compared to 9.1% in the conventional group) showed a positive “legacy effect” from lower blood sugar that resulted in:
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63% reduced risk of diabetes-related retinopathy (eye disease) after five years.
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54% reduced risk of kidney disease after five years.
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60% reduced risk of neuropathy (nerve damage) after five years.
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30% reduced risk of cardiovascular events (including heart attack and stroke) after 20 years.
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The risk of complications increased with higher A1C values.
Our takeaways from this data:
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DCCT ultimately found that the earlier intensive blood glucose therapy was introduced and maintained, the lower the risk of long-term complications even after both groups had about the same blood sugar – again, a very positive legacy effect (despite a great deal of hypoglycemia – CGM had not been developed). Historically, the downside of therapy has related to hypoglycemia, which is now much more manageable for people with CGM and people able to take insulins that are more stable.
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This data provided evidence that early, intensive diabetes management leads to lower risk for long-term complications. It also led to the recommendation that intensive therapy should be started as early as possible for people with type 1 diabetes.
The legacy effect in people with type 2 diabetes
The glucose legacy effect in people with type 2 diabetes was first identified in the UK Prospective Diabetes Study (UKPDS) through analysis of its ten-year follow-up observational study. UKPDS examined the long-term effects of blood glucose and blood pressure management in people with type 2 diabetes.
Here are the key findings from the glucose study:
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During the trial, the conventional blood glucose management group had an average A1C of 7.9%, while the intensive therapy group had an average A1C of 7.0%.
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With this within-trial 0.9 percentage point difference in A1C, people in the intensive therapy experienced:
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A 12% risk reduction in any diabetes-related endpoint (this included any condition that related to diabetes such as death from hyperglycemia or hypoglycemia, heart attack, stroke, etc.)
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A 25% risk reduction in microvascular complications (including kidney failure and eye disease)
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A 21% risk reduction in diabetes-related retinopathy after 12 years
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A 33% risk reduction in kidney disease after 12 years
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Even after both groups returned to an identical A1C during the ten-year follow-up, the people in the original intensive therapy group continued to have a significantly lower risk of diabetes complications. This is what researchers refer to as the glucose legacy effect.
Is there a legacy effect of changes in diet and exercise?
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Twenty and 30 years after the Da Qing prevention trial, the rates of health complications, including cardiovascular disease (CVD) and CVD deaths, were lower in people who had been in intervention groups for diet, exercise, or both.
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The Look AHEAD trial found that interventions for weight loss resulted in benefits for people with type 2 diabetes, including improved diabetes management with fewer drugs, lower risk for advanced chronic kidney disease, and lower risk for CVD with fewer drugs.
Experts have pointed out that legacy effects vary depending on the intervention effort and behaviors during follow-up studies. To learn more about diabetes-related health complications, click here.
This article is part of a series on time in range.
The diaTribe Foundation, in concert with the Time in Range Coalition, is committed to helping people with diabetes and their caregivers understand time in range to maximize patients' health. Learn more about the Time in Range Coalition here.
