The Legacy Effect in Type 2 Diabetes

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Immediate, intensive treatment for newly diagnosed diabetes patients may be necessary to avoid irreversible long-term risk for diabetic complications and mortality, a new study shows.

In the United States, an estimated 1.4 million adults are newly diagnosed with diabetes every year. For patients newly diagnosed with type 2 diabetes, the benefits of maintaining HbA1c (average blood glucose levels for the last 2-3 months) of <7.0% are well established.

Clinical trial long-term follow-up studies have demonstrated that early glycemic control has durable effects. However, prior to this study it was not clear whether legacy effects exist in real-world populations, how soon after diagnosis legacy effects may begin, or for what level of glycemic control legacy effects may exist.

Led by Neda Laiteerapong, M.D., of the University of Chicago and published in the March issue of Diabetes Care, the study utilized the Kaiser Permanente Northern California (KPNC) Diabetes Registry, which has maintained a cohort of patients with diabetes since 1993. The KPNC Diabetes Registry is notable for its ethnic diversity and sociodemographics.

Overall, the study included 34,747 patients diagnosed with type 2 diabetes between 1997 and 2003 who had survived at least 10 years after diagnosis. The study defined seven early exposure periods (0–1, 0–2, 0–3, 0–4, 0–5, 0–6, and 0–7 years) beginning with 3 months after the first measured HbA1c result. The mean HbA1c value for each of the seven early exposure periods was categorized into: <6.5%; 6.5% to <7.0%; 7.0% to <8.0%; 8.0% to <9.0%, or ≥9.0%.

The outcomes of interest were incident future advanced microvascular events (end-stage renal disease, diabetic eye disease, and lower-extremity amputation), macrovascular events (cerebrovascular disease, heart disease, heart failure, and vascular disease), and death. Models adjusted for sex, race/ethnicity, age at diagnosis, and year of diagnosis as well as for cardiovascular risk factors.

Among patients with 10 years of survival after type 2 diabetes diagnosis, researchers found that HbA1c levels ≥6.5% for the first year after diagnosis was associated with a greater risk of future diabetic complications compared with an HbA1c <6.5% for the first year after diagnosis. HbA1c levels ≥7.0% for the first year after diagnosis were associated with an increased risk of future mortality. Increasing periods of exposure to HbA1c levels ≥8.0% were associated with an increased risk of microvascular events and mortality.

A major limitation of this study is the researcher’s inability to comment on causality, as it is possible that HbA1c at the time of diagnosis reflects inherent differences in baseline disease severity or patient characteristics that determine long-term outcomes. Additionally, although researchers adjusted for year of diagnosis, the long follow-up period required for this study witnessed important secular changes in diabetes screening, intensity of glycemic control, and outcomes that may have affected the findings.

Nevertheless, “these findings underscore the urgency of early diagnosis of diabetes and the future consequences of failing to achieve near-normal glycemia soon after patients are diagnosed with diabetes,” the researchers conclude. “Treating patients with diabetes early and more intensively has the potential to confer substantial, long-term improvements in public health.” 

REFERENCES

Laiteerapong N, Ham SA, Gao Y, et al. “The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes & Aging Study).” Diabetes Care. March 2019. DOI: 10.2337/dc17-1144