The tighter the better

Aims: To evaluate the association of chronic complications with time in tight range (TITR: 3.9–7.8 mmol/l, 70-140 mg/dl) and time in range (TIR: 3.9–10.0 mmol/l, 70-180 mg/dl) in people with type 1 diabetes (T1D).

Methods: Retrospective cross-sectional analysis in 808 adults with T1D in Belgium (RESCUE and FUTURE studies). Logistic regression was used to evaluate the association between TITR/TIR and the presence of complications without adjustment, with adjustment for HbA1c, and with adjustment for HbA1c and other confounding factors.

Results: The mean TITR and TIR were 33.9±12.8% and 52.5±15.0%, respectively. The mean age was 44.8±15.2 years and the mean diabetes duration was 23.1±13.6 years. 46.0% of participants had one or more microvascular complications and 16.0% had diabetic peripheral neuropathy (DPN) (based on abnormality in monofilament sensation and/or in nerve conduction study). Each 10% increase in TITR was associated with a lower incidence of DPN (OR 0.837; 95% CI 0.717, 0.977; p=0.026). For TIR the results related to DPN were not statistically significant. A 10% increase in TITR or TIR was associated with 23.8% and 17.2% lower incidences, respectively, of any microvascular complication and 34.9% and 25.1% lower incidences, respectively, of cerebrovascular accident. The independent association of TITR with any microvascular complication and diabetic retinopathy persisted after adjustment for HbA1c but that with DPN did not.

Conclusions: TITR and TIR are inversely associated with the presence of microvascular complications and cerebrovascular accidents in people with T1D. The analysis adds validity to the use of TITR and TIR as key measures in glycemic management.

Comments: This study is among the first to explore the relationship between TITR and chronic diabetic complications, including DPN. TITR, defined by a narrower glucose range, introduces a novel metric for assessing glycemic variability, addressing the limitations of HbA1c.

The findings demonstrate a significant association between higher TITR and a reduced prevalence of DPN, emphasizing the value of tighter glucose regulation in lowering the risk for micro- and neurovascular complications. It is interesting to show that TITR and not TIR is related to the reduction of DPN; perhaps neuropathy is especially sensitive to greater fluctuations of glycemia and requires staying in normoglycemia as long as possible. However, when adjusting for HbA1c the predictive value of TITR for DPN was lost while it was retained for retinopathy.

Using a real-world, cross-sectional dataset enhances the study’s applicability to clinical practice. The research quantifies DPN risk reduction for 16.3% with each 10% increase in TITR, offering actionable insights for patient management. The study has a modern approach that better reflects glycemic variability by using continuous glucose monitoring (CGM)-derived metrics. While the cross-sectional design limits causality conclusions, it provides fundamentals for future longitudinal studies on TITR's long-term effects. The findings suggest TITR could become a key target in personalized diabetes management, influencing therapeutic strategies and guidelines.

The study underscores the clinical utility of TITR, particularly in light of advancements in automated insulin delivery systems, which could favor tighter glucose control and reduce the burden of complications like DPN. On the other hand, from a clinical point of view, such a strict pursuit of achieving TITR might have a negative impact on patients' emotions and their quality of life.

Aleksandra Araszkiewicz

Reference. De Meulemeester J, Charleer S, Visser MM, De Block C, Mathieu C, Gillard P. The association of chronic complications with time in tight range and time in range in people with type 1 diabetes: a retrospective cross-sectional real-world study. Diabetologia. 2024 Aug;67(8):1527-1535. doi: 10.1007/s00125-024-06171-y. Epub 2024 May 24. PMID: 38787436.

https://link.springer.com/article/10.1007/s00125-024-06171-y