DKA On The Rise: Dr. Satish Garg Explains Why
Dr. Satish K. Garg is a professor of Medicine and Pediatrics at the Adult Clinic of the Barbara Davis Center in Aurora, Colorado. He is an international lecturer, speaker and an accomplished author, having published more than 300 original manuscripts in peer-review journals. Dr. Garg was one of four featured experts during Beyond Type 1’s #KnowledgeDrop Series, discussing diabetic ketoacidsosis (DKA) and ketone management.
How did you get into endocrinology?
Next year is actually my 50th year anniversary of having gone to medical school and I have practiced medicine now for 45 years. My mom died of type 1 diabetes at a very young age—she was only 44 when she passed away. I’m talking about back in the 50s and the 60s, type 1 diabetes wasn’t really figured out because it was only 1922 that we came to have insulin. So they didn’t manage it well, plus on top of that, she was a strong Hindu, so she followed a lot of fasts and all of the Hindu festivals. They celebrated when I was born because I was very big, without realizing that she actually had type 1 diabetes all along—they didn’t even diagnose during the pregnancy. So unfortunately, she passed away when she was young on the day I graduated from medical school.
What has your journey been like, from working in endocrinology in India starting in the 1970s to now working at the Barbara Davis Center in Colorado?
When I was in India, I practiced medicine for about 10 years. At the Postgraduate Institute, I championed a program about how to transition diabetes care from childhood to adulthood, specifically focusing on diabetes in young women as their diabetes management was sub-optimal. The Barbara Davis Center (BDC) was started because Dana Davis was diagnosed with diabetes when she was 7 or 8. For the next 10 years, the BDC was only a pediatric center. They used to follow four hundred kids, but then afterwards when the kids became adults, they had no place to go.
There was a need for ongoing diabetes care for these kids who were now adults. In those days, there was no Pediatric Endocrinology back in India. So I championed this program: how to transition from Pediatrics in India … more than 30 years ago. I was recruited from India to help initiate the program at the Barbara Davis Center.
What was the frequency of DKA and diagnosis when you first arrived in America? Has the number of adults living with Type 1 who go into DKA or die from DKA gotten significantly better?
Fortunately, there was a time period during which the episodes of DKA significantly went down partly because of the advent of longer acting insulins e.g Levemir and glargine. That was the number one reason. You need very little insulin to stop DKA, so if you’ve got a longer acting insulin, you pretty much don’t get it. The resurgence of DKA came about in the US almost 35 years ago when people started using insulin pumps. In my view, insulin pumps in those days were really not well known. At that time, we didn’t know about catheter sites. We recommended changing insulin delivery catheters every two to three days. However, not many people did; they just kept going longer until their insulin ran out. Of course, education has helped since then but it wasn’t the case when they first hit the market. Now more recently, T1D Exchange data shows that DKA rates are lower in pump users as it represents more than 75 leading centers in the US
Are people with pumps still more likely to go into DKA?
If you look at all the three major studies done with SGLT2 inhibitors, my articles in NEJM and all the Diabetes Care manuscripts and the Lancet article, they clearly show the risk of DKA in pumpers in real life is two times higher compared to people who use just the long-acting insulin. The knowledge is not the same compared to centers like ours or any recognized places. The majority of pumps in adults are not initiated by endocrinologists in the US, they are usually started by the “diabetes specialists” and primary care physicians.
Over 70 percent of people with type 1 diabetes are adults. That’s another misnomer. I’ve had patients who are diagnosed at age 50 or 60 years (antibody positive type 1 diabetes).
15-20 percent of type 2 diabetes cases are misdiagnosed. These patients have antibody positive type 1 diabetes. So clearly their type 1 diabetes was totally mistreated and misdiagnosed. That’s why the actual number of people who are living worldwide who are insulin requiring is more like 150 to 200 million people, out of which probably closer to 70-80 million people actually have classical type 1 diabetes, if you define by antibody positive. They may not be totally deficient in beta cell mass because they are making some c-peptides. So, you can give some drugs and they’ll sort of chug along, but they truly do have type 1 diabetes.
Unfortunately, most primary care physicians and internal medicine doctors are not taught much about diabetes during their training. Since there is a huge shortage of endocrinologists, most of diabetes in adults, especially type 1 or insulin-requiring type 2, is taken care of by the primary healthcare provider or internists. Even many endocrinologists learn on the job regarding pump therapy, continuous glucose monitors (CGMs), etc.
What are some of the contributing factors leading to a higher incidence of DKA?
That actually brings me to the point of the T1D Exchange data, which shows the average risk of DKA is 5 percent. This is significantly higher than what it used to be. If you look at that data five years ago and now, it’s trending in the wrong direction. Of course, in people with poor blood glucose control, the risk is much higher. When you look at the European data, in the UK, the risk is 50 percent higher in the past 10 years, so the last decade it’s really gone up significantly. To come back to your point, there needs to be energy put into reeducating people about DKA.
And part of the problem is those on multiple daily injection (MDI) who miss their long-acting insulin. In those who take basal insulin reliably, DKA is more or less nonexistent, but that’s not the real world. The second big problem is the cost. I was shocked at how many people do not get reimbursement for blood ketone strips. It costs a dollar a strip—you and I know it costs a few pennies to make it. The urine strips are much cheaper and they are approved and available, but that’s not the ideal way to manage DKA in people who are in DKA, especially using off-label SGLT 2 inhibitors (approved for type 2 diabetes). Blood strips are the best way to go—that measures directly BOHB (beta-hydroxybutyric acid) which is what you want to measure.
Are you surprised that there hasn’t been any kind of oral medication or adjunct therapy for people living with Type 1 diabetes?
It’s sad because it’s now close to a hundred years after finding insulin, and there is no true adjunctive therapy available. Pramlintide is approved, but hardly used… The only class of drug that might actually have a possibility in type 1 diabetes is truly SGLT2 inhibitors because these are the only class of drugs that don’t require insulin for their action.
Do you think there is still hope that SGLTs might be approved?
It’s trending the wrong way. Remember when these trials in type 1 diabetes were started, we didn’t know about the DKA risk with these drugs. In all fairness to the companies, they did not mitigate the proper risk of DKA because it wasn’t known. Only in 2016 did the FDA add the warning risk for this class of drugs, even for patients with type 2 diabetes.
I’m not sure how soon in the US it will get approved. I know that companies have a different perspective. However, having said that, it will continue to be used off-label, I along with many others have many patients with type 1 diabetes who are using it off-label. The problem is, if you don’t educate patients enough regarding mitigation strategies for DKA, you are likely to have adverse outcomes. I take about half an hour to 45 minutes anytime I start somebody on any of these drugs to explain the risks versus the rewards. Most patients like being on these medications as it takes away highs and lows blood glucose levels (BGs) extremes commonly associated with type 1 diabetes. I always start on a smaller dose, gradually build it up, have them check blood ketones regularly, as blood glucose levels may not be high (euglycemic-normoglycemic DKA) as expected with DKA due to continued loss of glucose in the urine. Also, it is important to highlight in case of stress, planned surgery, ketogenic diets etc., that these drugs need to be discontinued due to a higher risk of DKA. Education is the key to success for reducing the overall risk of DKA with or without the use of these drugs.
This interview was part of Beyond Type 1’s #KnowledgeDrop Expert Video Series, made possible with support from Lexicon Pharmaceuticals.