Glycemic Variability Did Not Predict Complications in DCCT

Marlene Busko

April 25, 2017

In a new, more complete statistical analysis of data from the Diabetes Control and Complications Trial (DCCT) of patients with type 1 diabetes, having a wide variation in glucose readings was not an independent predictor of new or worsening microvascular complications after adjustment for mean glucose values.

Only 67% of patients in the DCCT had complete values for glucose profiles based on capillary blood samples taken at seven times during the day (before and after three meals and at bedtime).

The researchers used multiple imputations to estimate these missing values, unlike previous studies that have reported results only from patients with complete data.

"What is new is that we employed modern statistical methodology to account for all of the missing values" in the blood glucose profiles (using Profilsets, Boehringer-Mannheim Diagnostics), lead author John M Lachin, PhD, from the Biostatistics Center, George Washington University, Rockville, Maryland, told Medscape Medical News.

These analyses "fail to show that the within-day variability in blood glucose, when adjusted for the mean glucose, is associated with the development or progression of retinopathy, nephropathy, or [cardiovascular autonomic neuropathy]" in patients with type 1 diabetes in the DCCT, Dr Lachin and colleagues write in Diabetes Care, published online April 12, 2017.

However, "I wouldn't say patients should not worry about having wide variations in their glucose readings," Dr Lachin clarified.

"To me, the additional conclusion is that for patients to achieve their glucose targets, they also need to address the fact that a high degree of [glycemic] variation is going to work against them in reaching their goal.

"You can't have a mean glucose close to normal with an extreme level of variation," he added. "For example, it would be very difficult to maintain a mean blood glucose of, say, 170 mg/dL when the standard deviation of diurnal glucose is 75 mg/dL."

Glycemic Variability and Retinopathy, Nephropathy, or Neuropathy

From 1983 to 1993, the DCCT randomized 1441 patients with type 1 diabetes to intensive glucose-lowering therapy (designed to attain glucose levels as close to normal as possible) or to conventional glucose-lowering therapy.

The study showed that 6.5 years of intensive therapy markedly reduced the risks of onset and progression of microvascular complications of type 1 diabetes, which was almost completely explained by the differences in HbA1c levels.

However, the long-term effects of variability in glycemic control for patients in the DCCT was not clear.

Whereas data for the HbA1c values were virtually complete, 33% of the values for the seven-point glucose profiles, which were also obtained every 3 months, were missing.  

To examine the impact of glycemic variability on microvascular complications, Dr Lachin and colleagues used a statistical technique to calculate an average of 10 estimates for each missing value in the glucose profiles.

They examined how the patients' HbA1c levels and glycemic variability were associated with retinopathy, microalbuminuria, and cardiovascular autonomic neuropathy.

After adjustment for mean blood glucose levels, within-day glycemic variability was not significantly associated with these outcomes.

Only one measure of variability over the long term was associated with microalbuminuria, after correction for mean blood glucose.

The seven-point glucose profiles may not capture the full degree of glucose variability that might be seen with continuous glucose monitoring (CGM), the researchers acknowledge. However, the large data set and careful statistical imputations to address missing data may offset this weakness, they add.

"Overall, the measures of glycemic variability based on the complete quarterly seven-point glucose profile data sets fail to provide strong or consistent evidence that glycemic variability contributes to the risk of development or progression of microvascular complications beyond that contributed by the mean level of glucose," Dr Lachin and colleagues conclude.

The authors report that they have no relevant financial relationships.

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Diabetes Care. Published online April 12, 2017. Abstract


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