Greg Kinney, PhD, on Cannabis and Diabetic Ketoacidosis in Patients With Type 1 Diabetes

Findings published in Diabetes Care suggest that cannabis use may be associated with an increased risk for diabetic ketoacidosis (DKA) in patients with type 1 diabetes.¹

In their study, researchers analyzed data on cannabis use among 932 adults with type 1 diabetes from the T1D Exchange clinic registry (T1Dx).¹ They assessed the association between cannabis use, measured by total substance score (TSC) for cannabis, and DKA within the previous 12 months via a logistic regression model adjusted for potential confounders.¹ A total of 61 patients were moderate cannabis users, meaning they had a TSC above 4.¹

The results indicated that cannabis use was associated with a 2-times higher risk of DKA among adults with type 1 diabetes compared with non-use, following adjustment for sex, age at study visit, and hemoglobin A_1c (odds ratio 2.5).¹

Endocrinology Consultant discussed these findings and their implications further with lead study author Gregory Kinney, PhD, research assistant professor in the Department of Epidemiology at the University of Colorado Anschutz Medical Campus in Aurora, Colorado.

Endocrinology Consultant: What prompted you and your team to conduct this study?

Dr Kinney: Clinicians at the Barbara Davis Center for Childhood Diabetes (BDC) observed and reported repeated DKA in 2 of their patients with type 1 diabetes, which prompted them to begin a survey study of the patient population of the BDC in order to assess the extent of cannabis use in their patient population.^2,3 Daniel Taylor, a doctoral student in epidemiology, and I worked with them to analyze these data, where we observed an association between cannabis use and DKA.³

Since both observations involved BDC patients, we were interested in replicating the results in an independent population. To do this, we collaborated with T1Dx, where similar data were collected. It is important to note that the measure of cannabis use in T1Dx and the BDC patient populations were different, but the assessment of DKA was the same.

Endocrinology Consultant: Did you anticipate these findings?

Dr Kinney: We tested our null hypothesis, which was that there is no association between cannabis use and DKA. Ultimately, we rejected this hypothesis. It could have gone either way.

The BDC is located in Colorado, where cannabis has been legal for medical and recreational use for several years now. We initially thought that the BDC patient population living in Colorado may be different in terms of their exposure to cannabis, as well as their exposure to their diabetes treatment. This was not what we found though. We believe that this observation is evidence that there may be a biological mechanism linking cannabis to DKA that is generalizable to the larger population of people with type 1 diabetes.

Endocrinology Consultant: Did you assess specific components of cannabis separately in your study, and if so, did any specific components contribute differently to diabetic ketoacidosis risk?

Dr Kinney: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) Total Substance Score for Cannabis was used in the T1Dx cohort.⁴ This test is used to determine a risk score for each substance used and then initiate a discussion with patients about their substance use.⁴ The score can also be used to determine an appropriate intervention, if needed.⁴

Our work measured behavior related to cannabis use in the context of problematic use, whereas T1Dx did not measure cannabis or its components directly.

Endocrinology Consultant: Is the mechanism between cannabis use and diabetic ketoacidosis in type 1 diabetes yet known, or is this an area for further research?

Dr Kinney: The link between cannabis use and DKA is very likely multifactorial and could include aspects that involve the exposure itself, as well as biological and behavioral risk for the outcome. The exposure is complex, with people making choices as to the cannabis varietal to use, use method, frequency and timing of dosing, and the amount used at any given time. The outcome is serious and involves many aspects of treatment and management of the diabetic milieu. A fairly straightforward hypothesis to test might be that being “high” interferes with glycemic management. This implies to me that cannabis use should be associated with both DKA and hypoglycemic events and we don’t see an association with cannabis use and hypoglycemic events in either the BDC or T1Dx populations.

A potential mechanism that I find intriguing was mentioned by Kim Carmichael, MD, where he points out that the “use of cannabinoid agents may also be associated with symptoms similar to gastroparesis.”⁵ If cannabis use alters gastric emptying this may affect the timing and dose of insulin necessary for a given caloric exposure in an unanticipated way. These are areas for further research.

Endocrinology Consultant: Do these findings yet have a clinical application, or is it too early to say?

Dr Kinney: Making the jump from a statistical association to clinical recommendation will require far more evidence than this work has generated. It is important that we not over-interpret association studies like this one, but instead use them to generate testable biological hypotheses.

—Christina Vogt

References:

1. Kinney GL, Akturk HK, Taylor DD, Foster NC, Shah VN. Cannabis use is associated with increased risk for diabetic ketoacidosis in adults with type 1 diabetes: findings from the T1D Exchange Clinic Registry. Diabetes Care. 2019;42(11). https://doi.org/10.2337/dc19-0365
2.  Gallo T, Shah VN. An Unusual Cause of Recurrent Diabetic Ketoacidosis in Type 1 Diabetes. Am J Med. 2016;129(8):e139-140. doi:10.1016/j.amjmed.2016.02.033
3. Akturk HK, Taylor DD, Camsari UM, Rewers A, Kinney GL, Shah VN. Association between cannabis use and risk for diabetic ketoacidosis in adults with type 1 diabetes. JAMA Intern Med. 2019;179(1):115-118. doi:10.1001/jamainternmed.2018.5142
4. The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST)Manual for use in primary care. World Health Organization. 2010. Accessed November 4, 2019; https://apps.who.int/iris/bitstream/handle/10665/44320/9789241599382_eng.pdf;jsessionid=E5A7029DB4E4DC03CE911F39ADF53D0B?sequence=1.
5. Carmichael KA. What do you need to know about diabetic gastroparesis? Consultant. 2018;58(10):281-282. https://www.consultant360.com/article/endocrinology/diabetes/what-do-you-need-know-about-diabetic-gastroparesis