The HbA1c value is considered the gold standard for blood glucose monitoring in patients with diabetes, but it also has some limitations. US scientists have conducted a study to determine whether the blood glucose "time span within the normal range" of 70-180 mg/dl is a possible alternative to predict microvascular complications such as retinopathy and nephropathy.
HbA1c has become accepted as a tool for blood glucose control in patients with diabetes after the DCCT study (Diabetes Control and Complications Trial) showed a strong association with chronic vascular diabetes complications. The value can now be determined with great precision and has proven to be an accessible parameter or endpoint in practice and in clinical studies.
Since the mean value is based on hyperglycemia, no hypoglycaemic phases can be detected in individual patients and the glycaemic variability and daily profile are not shown. This is of minor importance when comparing groups within clinical studies, but could have a major impact on the management of individual patients.
In addition, the significance of the HbA1c value may be limited by numerous factors. These include hemoglobinopathies, hemolytic anemia, and chronic renal failure.
With the increasing spread of continuous glucose monitoring (CGM), other parameters such as the time in the "normal range" of 70-180 mg/dl (TIR for "time in range") have also come into focus. TIR is also mainly determined by hyperglycemia and therefore correlates well with the HbA1c value. So far, however, no association with diabetic complications has been proven for the TIR.
This is the task of Roy W. Beck from Tampa, Florida, USA, and his research group. They used data from the DCCT study. Here, the blood glucose values of the 1,440 participants were available seven times a day and were determined once a month. From these values, a TIR can be calculated approximately, although not as accurately as with CGM. The TIR thus determined was related to the progression of retinopathy controlled every six months and the development of microalbuminuria, which was determined every 12 months.
The average TIR was 41 ± 16%. The less time the patients spent within the normal range, the greater the risk of microvascular complications. For each 10% lower TIR, the scientists found an increase of 64% in retinopathy progression and 40% in microalbuminuria. TIR was significantly higher in the group with intensified therapy compared to conventional therapy (52 vs. 31%).
Thus, there is a strong association between TIR and the development of microvascular complications. This means that TIR is also an acceptable endpoint in clinical trials, especially if the parameter can be easily determined when using CGM, according to the authors. In addition, the association is expected to be even stronger when using more accurate CGM.
Source:
Roy W. Beck et al; Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials; Diabetes Care 2019 Mar; 42(3): 400-405. https://doi.org/10.2337/dc18-1444