Time in Range Inversely associated with All-cause and Cardiovascular Mortality in Patients with Type 2 Diabetes Mellitus

23 Feb, 21

Introduction

Time in range (TIR), an emerging metric for glycemic control assessment provides important information that cannot be captured by glycosylated hemoglobin (HbA1c). In recent times, increasing amount of evidence has been strengthening the association between TIR and diabetes related outcomes. Nevertheless, the association between TIR and mortality among patients with type-2 diabetes mellitus (T2DM) has not been explored till date.

Aim

To explore the association between TIR and mortality and cardiovascular (CV) mortality in patients with T2DM

Patient Profile

Adult patients with T2DM following a stable glucose lowering regimen for last 3 months and having data on TIR (n=6225)

Methods

Study Design

A prospective cohort study

Assessments

TIR (defined as percentage of time in target glucose range of 70-180 mg/dL during a 24-hour period) was assessed using a continuous glucose monitoring (CGM) system during a 3-day period
TIR was evaluated into following four categories:
- ≤50%
- 51–70%
- 71–85%
- >85

Outcomes

All-cause mortality
CVD mortality

Follow-up

Median period of 6.9 years

Results

The mean age of the study population was 61.7 years at baseline.
A total of 838 deaths were recorded during the study period, of these, 287 were attributed to CV diseases.
As per a multivariable-adjusted analysis, different levels of TIR were associated with all-cause mortality (P for trend <0.001) and CV mortality (P for trend = 0.015) (Table 1).

Table 1: HRs for all-cause and CV mortality as per the TIR range

TIR	aHR for all-cause mortality (95% CI)	aHR for CVD mortality (95% CI)
>85% (reference group)	1.00	1.00
71–85%	1.23 (0.98–1.55)	1.35 (0.90–2.04)
51–70%	1.30 (1.04–1.63)	1.47 (0.99–2.19)
≤50%	1.83 (1.48–2.28)	1.85 (1.25–2.72)

aHR; adjusted hazard ratio, CI; confidence interval

Factors such as age, history of CV disease or cancer, use of insulin, and use of antihypertensive drugs had no significant influence on the association between TIR and the risk of all-cause mortality. Gender (P for interaction <0.05) significantly influenced the association between TIR and the risk of all-cause mortality.

Conclusions

Amongst patients with T2DM, TIR assessed by CGM during hospitalization was inversely associated with long-term risk of all-cause and CV mortality
The findings support the validity of TIR as a surrogate marker of long-term adverse clinical outcomes in patients with T2DM.
Patients with diabetes should be encouraged to target an achievable higher TIR to diminish the risk of adverse clinical outcomes.

Diabetes Care 2021;44:549–555.