Could CGM dethrone HbA_1c for office-based diabetes care?

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In fact, he suggested, “Maybe it’s not just the absolute level of A_1c” that is increasing the chances of complications. “Maybe it’s how much that A_1c varies over time.” Variability in the measurements of HbA_1c has been shown in some studies to be a stronger predictor of risk of complications than just the absolute mean of the HbA_1c over time, he said.

That’s one of the reasons Dr. Bergenstal’s clinic is studying the data it’s collecting from continuous glucose monitoring of patients. Displaying a chart tracking patients’ blood glucose levels from midnight to midnight, he pointed to one patient who had 25 percent of glucose values from 2 AM to 4 AM down near 50 every night, on average, for two weeks. Those data clearly mean one thing to him: “I’ve got to address those low blood sugars that could kill this patient or result in a coma or something else. I don’t care what their A_1c is,” he said.

Similarly, a comparison of three patients with the same HbA_1c showed strong differences in their glucose variations. One was taking four injections a day, one used a pump to deliver insulin, and the third was in a recent trial at the clinic of a so-called artificial pancreas (using computer-driven algorithms to inject insulin based on what the glucose is). “Their glucose fluctuations are completely different. So is their rate of hypoglycemia and their time in range—a measure we’re talking a lot about, meaning how much time do you spend in the target range.” These variations raise a key question: “How did they get these different levels of improvement with the same A_1c but a more unstable glucose profile?”

His clinic uses such day-to-day data to study people with type 1 diabetes and, increasingly, people with type 2 diabetes. “We’re starting to look at CGM very early in the diagnosis as well. You can look at each patient’s data and see each one has their own story. I know we’ve talked about precision medicine in cancer, but this is precision medicine in diabetes. You can look at a picture of the data and know what to do.”

Dr. Bergenstal is convinced that CGM addresses a broader range of issues than just HbA_1c. “There are more than just long-term complications with diabetes. There are day-to-day short-term complications such as hypoglycemia. There is a lot of burden to living with this disease that A_1c doesn’t really get to.”

He is eager to see researchers have a standard way to look at and describe the data. “We need a CGM standardization project. The A_1c is a great marker of long-term complications. But CGM is better for short-term complications, easing the burden of diabetes, quality of life, better guiding you in personalizing management, and helping us individualize our targets.”

Dr. Sacks

CGM provides a huge amount of information that can be useful, Dr. Sacks says, but the downside is its expense. “You have to get this needle, you have to put the needle under their skin, and then you have to change the needle periodically and patients need to be very motivated.” For example, studies show it doesn’t work well in most teenagers, he says. “And many countries—I would say most countries—cannot afford CGM for many patients with diabetes.”

Estimating HbA_1c via CGM is also not a substitute for measuring it in the laboratory, Dr. Sacks emphasizes. “The CGM is used for estimating how much insulin to give.” Patients with diabetes have been taught for years to know their ABCs: A (HbA_1c), B (blood pressure), and C (cholesterol). “So most clinicians can talk to their patients and say, based on their CGM over the last month, what their estimated HbA_1c would be.” But whether estimated HbA_1c, or the glucose management indicator, is a better predictor of complications than laboratory HbA_1c has not been studied yet, Dr. Sacks says. Answering that question will require a long-term trial with millions of dollars of funding.

Since the AACC meeting last summer, Dr. Bergenstal tells CAP TODAY, two studies have been published showing good correlation for the time patients spend in the target range, based on CGM, and eye and kidney complications (Beck RW, et al. Diabetes Care. Published online Oct. 23, 2018. doi:10.2337/dc18-1444; Lu J, et al. Diabetes Care. 2018;41[11]:2370–2376). “While not the definitive long-term study Dr. Sacks is looking for,” he says, “it is early data showing the potential value of CGM in predicting diabetes complications.”

Dr. Bergenstal agrees that continuous glucose monitoring is expensive. “But it is getting better and simpler. Now some of the devices require no calibration. It costs $120 a month to have continuous glucose data and it can go straight up to the cloud” to be shared with clinicians, who could eventually confer with their patients online much more efficiently than through office visits. He thinks the expense also has to be weighed against many benefits. Already at his clinic, for example, “some patients on continuous glucose monitoring are stopping medications costing $600 a month that we thought were working, but weren’t,” he said.

With continuous glucose monitoring, Dr. Bergenstal said, “It’s looking like the whole office-based model of diabetes care needs to change.”

Anne Paxton is a writer and attorney in Seattle.