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. 2021 Aug 11;44(10):2225-2230.
doi: 10.2337/dc21-1331. Online ahead of print.

The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes

John M Lachin  1 , Ionut Bebu  2 , David M Nathan; DCCT/EDIC Research Group
Affiliations

The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes

John M Lachin et al. Diabetes Care. .

Abstract

Objective: The principal aim is to estimate the benefits of earlier versus later implementation of intensive therapy in type 1 diabetes with respect to the long-term risks of progression of a renal (microvascular) and cardiovascular (macrovascular) complication in the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

Research design and methods: Cox proportional hazards regression models estimated the 20-year cumulative incidence (absolute risk) and the 20-year relative risk of cardiovascular disease (CVD) and reduced estimated glomerular filtration rate (eGFR) over the first 20 years of EDIC follow-up as a function of the mean HbA1c.

Results: A hypothetical patient treated earlier with 10 years of intensive therapy and a mean HbA1c of 7% (53 mmol/mol) followed by 10 years with a mean of 9% (75 mmol/mol) would have a 33% reduction in the risk of CVD and a 52% reduction in reduced eGFR compared with a patient with a mean HbA1c of 9% (75 mmol/mol) over the first 10 years followed by later intensive therapy over 10 years with an HbA1c of 7% (53 mmol/mol). Despite both patients having the same average glycemic exposure over the 20 years, the patient with the lower HbA1c over the first 10 years had a lower risk of progression of complications over the 20 years than the patient who had the higher value initially.

Conclusions: While implementation of intensive therapy at any time in type 1 diabetes will be beneficial, within the 20-year period modeled, earlier relative to later implementation is associated with a greater reduction in the risks of kidney and cardiovascular complications.

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Figures

Figure 1
Figure 1
The smoothed empirical (model-free) estimate of the underlying relationship between the log hazard (risk) of CVD and reduced eGFR (<60 mL/min/1.73 m2) with the updated weighted mean HbA1c that represents virtually a linear relationship that would be represented by a linear term in the Cox PH model. The reduced eGFR panel is based on the full cohort over 20 years.
Figure 2
Figure 2
The cumulative incidence of any CVD and reduced eGFR over the first 20 years of follow-up in EDIC (solid line) and 95% CI estimated from the Cox PH model in conjunction with the Breslow estimate of the underlying hazard function compared with the empirical Kaplan-Meier estimate of the cumulative incidence function (dashed line), the two estimates being virtually identical. The model for reduced eGFR used a separate coefficient for the mean HbA1c within each 10-year period.
See this image and copyright information in PMC

Comment in

References

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