Further Evidence - Maintaining Tighter Blood Glucose Control Reduces Complications

Managing Type 1 diabetes is a complex and ongoing challenge that involves maintaining blood glucose levels within a target range to prevent complications and improve quality of life.

The landmark Diabetes Control and Complications Trial (DCCT) demonstrated that near-normal blood glucose levels reduced the development and progression of retinopathy, nephropathy, and neuropathy.

A recent study which evaluated the association of chronic complications with time in tight range and time in range in people with Type 1 diabetes further highlights the goal of Type 1 diabetes management which is to maintain blood glucose levels as close to physiologically normal as possible.

This blog article we'll explore the latest research findings, which highlight the importance of striving for normal, stable blood glucose levels to minimize health complications, and delve into the history of Time in Range (TIR) and Time in Tight Range (TITR) for those with Type 1 diabetes.

History of Time in Range (TIR) and Time in Tight Range (TITR)

The Landmark DCCT Study

The Diabetes Control and Complications Trial (DCCT), conducted in the 1980s and 1990s, was a pivotal study that established the critical relationship between intensive diabetes management and the delay or prevention of microvascular complications. This trial highlighted the importance of tight glycemic control and striving for near-normal blood glucose levels in managing Type 1 diabetes. The DCCT demonstrated that lower HbA1c levels, closer to normal, non-diabetic HbA1c levels were associated with a reduced risk of complications such as retinopathy, nephropathy, and neuropathy.

The Rise of Continuous Glucose Monitoring (CGM)

Over the past decade, the advent and widespread adoption of continuous glucose monitoring (CGM) technology has revolutionized diabetes management. CGM devices provide real-time data on blood glucose levels, allowing individuals and healthcare providers to monitor and adjust treatment more effectively. With the rise of CGM use, the clinical community have enabled the classification of sensor glucose levels into various ranges, giving rise to the metrics of TIR and TITR.

Goals of Type 1 diabetes Management

The primary goal of Type 1 diabetes management is to achieve and maintain normal blood glucose levels to prevent or delay the onset of complications. This involves keeping blood glucose levels within a target range as much as possible. The clinical community established TIR to be used alongside HbA1c to provide a more comprehensive picture of glycemic control, reflecting the percentage of time that an individual's blood glucose levels are within the desired range.

Definition of Time in Range (TIR)

TIR denotes the percentage of time that an individual's blood glucose levels are within the target range of 70-180 mg/dL (3.9-10.0 mmol/L). This metric provides a detailed view of daily glucose fluctuations, capturing both high and low glycemic excursions that HbA1c cannot reflect.

Why TIR is Being Used and Recommended

The clinical community has established that TIR is considered more reflective of the lived experience of people with diabetes, as it provides a more granular view of blood glucose control throughout the day. This metric can guide more precise adjustments in diabetes management, helping to reduce glycemic variability and minimize both hyperglycemia and hypoglycemia.

Evidence of a Decrease in Complications by Achieving a Certain TIR

The DCCT study showed that HbA1c levels are strongly associated with the development of microvascular complications. A higher than normal HbA1c was associated with a significant increase in the risk of complications such as retinopathy and microalbuminuria. Subsequent research has confirmed these findings as related to TIR, demonstrating that lower TIR is associated with more severe diabetic retinopathy and increased carotid intima-media thickness, a marker of atherosclerosis. Please note that lower TIR means the number of hours one's blood glucose levels are in range. The lower the number of hours the greatest the associated risk of developing health complications.

Shortcomings of Time in Range

TIR is increasingly being accepted in clinical practice guidelines and research protocols, with ongoing efforts to standardize its use and interpretation.

Despite its advantages, TIR has limitations.

It does not provide information on the timing and duration of glucose excursions, which can be critical for managing diabetes. Additionally, there is still a need for consensus on the minimum data requirements for TIR to be considered clinically valid in research and practice. Furthermore, while CGM technology is becoming more accessible, it may not yet be available to all people with diabetes, potentially excluding some patients from optimal management.

Additionally, TIR could potentially be misinterpreted as the ultimate goal of managing Type 1 diabetes, suggesting that these ranges are what the body naturally wishes to maintain for optimal health. While TIR provides valuable metrics that provide insights into glycemic control and help reduce the risk of complications, they are tools to achieve broader management goals rather than end goals in themselves, which is to safely achieve stable, normal blood glucose levels similar to those of someone not diagnosed with Type 1 diabetes.

Key Findings from Recent Research on Time in Tight Range (TITR) and Time in Range (TIR)

A recent study titled "The association of chronic complications with time in tight range and time in Range in People with T1D: a retrospective cross-sectional real-world study" provides valuable insights into any significant associations between maintaining tighter control, as measured by TITR and TIR in managing Type 1 diabetes.

Method of the Study

Study Design:

The study is a retrospective cross-sectional real-world study. This means it analyzed existing data from past records rather than collecting new data prospectively.

Data Collection:

->Data was collected from continuous glucose monitoring (CGM) devices to determine the percentage of time participants spent within the defined glycemic ranges (TIR and TITR).
-> HbA1c levels were measured to correlate with TIR and TITR data.

Analysis:

->The study assessed the association between TITR/TIR and the presence of chronic complications, including both microvascular and macrovascular complications.
-> The associations were adjusted for various confounding factors to ensure robust results.

Difference Between TIR and TITR and the Consideration for TITR Definitions

-> Time in Range (TIR): The percentage of time that an individual's blood glucose levels are within the range of 3.9–10.0 mmol/L.
-> Time in Tight Range (TITR): The percentage of time that an individual's blood glucose levels are within a narrower range of 3.9–7.8 mmol/L.

Groups Studied

Time in Tight Range (TITR) Group:

-> Definition: Participants who spent a higher percentage of time within the tight range of 3.9–7.8 mmol/L.
-> Mean TITR: 33.9 ± 12.8%.
-> Mean HbA1c: 7.7 ± 1.1% (61 ± 12 mmol/mol) for participants with higher TITR percentages compared to 8.2 ± 1.2% (66 ± 13 mmol/mol) for those with lower TITR percentages.

Time in Range (TIR) Group:

-> Definition: Participants who spent a higher percentage of time within the range of 3.9–10.0 mmol/L.
-> Mean TIR: 52.5 ± 15.0%.
-> Mean HbA1c: 7.7 ± 1.1% (61 ± 12 mmol/mol) for participants with higher TIR percentages compared to 8.2 ± 1.2% (66 ± 13 mmol/mol) for those with lower TIR percentages.

Association with TITR and TIR

Microvascular Complications

The study found a decreased prevalence of microvascular complications with higher TITR/TIR quartiles. Specifically:

TITR:
-> Each 10% increase in TITR was associated with lower incidences of any microvascular complication (OR 0.762), diabetic retinopathy (OR 0.757), background diabetic retinopathy (OR 0.760), severe diabetic retinopathy (OR 0.854), diabetic nephropathy (OR 0.799), DPN (OR 0.837), and cerebrovascular accident (CVA) (OR 0.651).
-> TITR remained an independent risk factor for microvascular complications even after adjusting for HbA1c and other confounding factors.

TIR:

-> Each 10% increase in TIR was also associated with a lower incidence of similar microvascular complications. However, the association was generally less strong than for TITR.

Macrovascular Complications

The study observed a significant association between TITR and CVA but not with other macrovascular complications. Similarly, TIR showed a significant association with CVA but not with other macrovascular complications.

HbA1c Data

HbA1c showed limited predictive performance compared to TITR and TIR. After adjusting for HbA1c and other risk factors, the predictive ability improved, but TITR and TIR still showed an independent association with diabetic retinopathy, background diabetic retinopathy, and CVA.

Conclusion from the Study

The study provides strong evidence that both TITR and TIR are inversely associated with the presence of microvascular complications and CVA in people with Type 1 diabetes. This suggests that maintaining higher TITR and TIR can significantly reduce the risk of these complications. Although HbA1c remains a critical metric, TITR and TIR are used as complementary measures in glycemic management to provide a more comprehensive assessment and help prevent chronic complications.

Overall Conclusion

The study shows that blood glucose levels held within a tighter range exhibit better health outcomes, providing further evidence that the goal of Type 1 diabetes is to safely achieve stable, normal blood glucose levels similar to those of someone who does not have a Type 1 diabetes diagnosis.

⚠️ T1D Nutrition wishes to make it clear that the values and ranges established via TIR and TITR should NOT be misinterpreted as the goal of Type 1 diabetes management. Unless your TIR/TITR values are set to normal non-diabetic blood glucose numbers, TIR/TITR are clinical reference points set by your diabetes care team and are much higher than normal blood glucose levels which the body wishes to naturally maintain for optimal health. The Mean HbA1c within the TITR group of the study was 7.7% ± 1.1%, which is an average daily blood glucose levels of 174mg/dl or 9.7mmol/l which is 44% higher than the Mean HbA1c of 4.99%, of US children and young adults not diagnosed with Type 1 diabetes aged 5 - 24 (10.2337/diacare.25.8.1326 ). 

🎯 If you are interested in improving your child's Type 1 diabetes management and successfully implementing a Therapeutic Carbohydrate Reduction/low-carb nutrition strategy, so you can safely achieve normal blood sugar levels, relieve stress, anxiety, and frustration, and nourish your child's growing body, visit:

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REFERENCES:

De Meulemeester, J., Charleer, S., Visser, M. M., De Block, C., Mathieu, C., & Gillard, P. (2024). 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. doi:10.1007/s00125-024-06171-y

Hirsch, I. B., Sherr, J. L., & Hood, K. K. (2019). Connecting the dots: Validation of time in range metrics with microvascular outcomes. Diabetes Care, 42(3), 345–348. doi:10.2337/dci18-0040

Timmons, J. G., Boyle, J. G., & Petrie, J. R. (2021). Time in range as a research outcome measure. Diabetes Spectrum, 34(2), 133–138. doi:10.2337/ds20-0097