<b>When does metabolic memory start? Insights from the AMD Annals Initiative on stringent HbA1c targets.</b>

<p dir="ltr">Abstract </p><p dir="ltr">Early, intensive glycemic control in T2D patients is associated with long-term benefits on cardiovascular disease (CVD) development. Evidence on benefits of achieving HbA1c targets close to normal values is scant. Subjects with newly-diagnosed T2D, without CVD at baseline, were identified in an Italian clinical registry (N=251,339). We adopted three definitions of early exposure periods (0–1, 0–2 and 0–3 years). Mean HbA1c was categorized into HbA1c < 5.7%, 5.7-6.4%, 6.5-7.0%, 7.1-8.0%, and >8.0%. The outcome was the incidence of major cardiovascular events. After a mean follow-up of 4.6±2.9 years, at multivariate Cox regression analysis, compared with mean HbA1c <5.7% during the first year after diagnosis, the increase in the risk of CVD was 24%, 42%, 49% and 56% for patients with HbA1c of 5.7%-6.4%, 6.5%-7.0%, 7.1%-8.0%, and >8.0%, respectively. The same trend was documented in all exposure periods. In conclusion, our data support that an early achievement of stringent targets of HbA1c <5.7% is worthy for CVD prevention. </p><p dir="ltr"><br></p><p dir="ltr">Highlights · Why did we undertake this study? </p><p dir="ltr">The CVD impact of achieving very strict HbA1c targets soon after the T2D diagnosis is unknown. · </p><p dir="ltr">What is the specific question(s) we wanted to answer? </p><p dir="ltr">Would near- normal mean HbA1c levels 1-3 years after T2D diagnosis reduce CVD risk? · </p><p dir="ltr">What did we find? </p><p dir="ltr">Compared with mean HbA1c <5.7% during the first year after diagnosis, CVD risk the was 24%, 42%, 49% and 56% higher for patients with HbA1c of 5.7%-6.4%,or above. · </p><p dir="ltr">What are the implications of our findings? </p><p dir="ltr">Early achievement of HbA1c <5.7% is associated with a lower incidence of CV events.</p>