Association Between Cannabis Use and Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes | Acid Base, Electrolytes, Fluids | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Table 1.  Characteristics of Adults With Type 1 Diabetes by Cannabis Use
Characteristics of Adults With Type 1 Diabetes by Cannabis Use
Table 2.  Primary Outcome of Diabetic Ketoacidosis in the Previous 12 Months Among Cannabis Users vs Nonusers With Type 1 Diabetes
Primary Outcome of Diabetic Ketoacidosis in the Previous 12 Months Among Cannabis Users vs Nonusers With Type 1 Diabetes
1.
Hasin  DS, Sarvet  AL, Cerdá  M,  et al.  US adult illicit cannabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013.  JAMA Psychiatry. 2017;74(6):579-588. doi:10.1001/jamapsychiatry.2017.0724PubMedGoogle ScholarCrossref
2.
Jadoon  KA, Ratcliffe  SH, Barrett  DA,  et al.  Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study.  Diabetes Care. 2016;39(10):1777-1786. doi:10.2337/dc16-0650PubMedGoogle ScholarCrossref
3.
Penner  EA, Buettner  H, Mittleman  MA.  The impact of marijuana use on glucose, insulin, and insulin resistance among US adults.  Am J Med. 2013;126(7):583-589. doi:10.1016/j.amjmed.2013.03.002PubMedGoogle ScholarCrossref
4.
Gallo  T, Shah  VN.  An unusual cause of recurrent diabetic ketoacidosis in type 1 diabetes.  Am J Med. 2016;129(8):e139-e140. doi:10.1016/j.amjmed.2016.02.033PubMedGoogle ScholarCrossref
5.
Adamson  SJ, Kay-Lambkin  FJ, Baker  AL,  et al.  An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test-Revised (CUDIT-R).  Drug Alcohol Depend. 2010;110(1-2):137-143. doi:10.1016/j.drugalcdep.2010.02.017PubMedGoogle ScholarCrossref
6.
Monte  AA, Zane  RD, Heard  KJ.  The implications of marijuana legalization in Colorado.  JAMA. 2015;313(3):241-242. doi:10.1001/jama.2014.17057PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Research Letter
    January 2019

    Association Between Cannabis Use and Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes

    Author Affiliations
    • 1Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora
    • 2School of Public Health, University of Colorado Anschutz Medical Campus, Aurora
    • 3Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
    JAMA Intern Med. 2019;179(1):115-118. doi:10.1001/jamainternmed.2018.5142

    Cannabis use is increasing with the shifts in legality and public perceptions in the United States.1 Studies have reported improvement in insulin sensitivity and pancreatic beta cell function with cannabis use,2,3 generating widespread media attention suggesting cannabis as a potential therapeutic agent for treatment of type 2 diabetes. By contrast, we published a case series4 reporting recurrent diabetic ketoacidosis (DKA) with cannabis use in patients with type 1 diabetes (T1D). Because little is known about cannabis use and its contribution to DKA in T1D, we investigated the characteristics of cannabis use among adults with T1D and the association of cannabis use with DKA.

    Methods

    Between June 2017 and January 2018, adults aged 18 years or older with T1D attending the Barbara Davis Center for Diabetes, the largest T1D treatment center in Colorado, where cannabis is legal for medical and recreational use, were invited to complete an in-person questionnaire on their cannabis use. Patients with diabetes other than T1D, pregnancy, and repeat follow-up visits within the study duration were excluded. A questionnaire was used to collect demographic characteristics, diabetes history and complications, severe hypoglycemia requiring assistance, and cannabis use information. Point-of-care hemoglobin A1c level (HbA1c; DCA Vantage Analyzer) was measured during the clinic visit. Scores on the Cannabis Use Disorder Identification Test-Revised5 were used to define hazardous cannabis use (score ≥8 and <12) and possible cannabis use disorder (score ≥12). The Colorado Multiple Institutional Review Board (Aurora, Colorado) approved this study, and all participants provided written informed consent.

    The primary outcome was DKA hospitalization during the preceding 12 months. All self-reported DKA hospitalizations were confirmed by medical record review. Comparison of categorical variables was conducted with 2-tailed χ2 tests, and 2-sample t tests were used to test normally distributed continuous variables. A logistic regression model was built to calculate the odds of DKA hospitalization by cannabis use. Clinical evidence-based risk factors for DKA, such as age, sex, diabetes duration, income, educational level, HbA1c level, and insurance (derived from income), were modeled, and a stepwise selection method was used to confirm the final model. Model fit was assessed by Akaike information criterion. Sensitivity analyses were performed using propensity score matching of cannabis users and nonusers, adjusting for age, sex, ethnicity, tobacco and alcohol use, educational level, income, employment, diabetes duration, HbA1c level, and use of diabetes technology. Residual confounding was controlled by including significant variables in the final logistic regression model. All analyses were conducted using SAS, version 9.4 (SAS Institute Inc). A 2-sided P < .05 was considered statistically significant.

    Results

    Of the 631 eligible patients, 450 (71.3%) responded to the survey. The mean (SD) age (36.8 [13.8] vs 34.6 [11.9] years, P = .07), sex (female, 201 [44.6%] vs 86 [47.5%]; P = .10), mean (SD) diabetes duration (19.5 [12.9] vs 18.3 [12.1] years, P = .22) and mean (SD) HbA1c level as percent of total hemoglobin (7.8% [1.8%] vs 7.8% [1.2%], P = .72; to convert HbA1c to proportion of total hemoglobin, multiply by 0.01) were similar between responders and nonresponders. Among 450 T1D participants, 134 (29.8%) reported using cannabis. Cannabis use duration, frequency, and form are shown in Table 1. Cannabis users were younger (entire cohort mean [SD] age, 31.3 [11.1] vs 39.1 [14.2] years), had lower income and educational levels, and shorter duration of diabetes (entire cohort mean [SD] duration, 16.3 [11.2] vs 20.9 [13.6] years) than nonusers (Table 1).

    In adults with T1D, cannabis use within the previous 12 months was associated with an increased risk of DKA compared with no cannabis use (entire cohort OR, 1.98; 95% CI, 1.01-3.91) (Table 2). Compared with nonusers with T1D, the mean (SD) HbA1c level (8.4% [2.0%] vs 7.6% [1.6%], P < .01) was higher but there was no difference in severe hypoglycemia (21 of 134 [15.6%] vs 64 of 316 [20.3%], P = .17) among cannabis users with T1D. Cannabis users had a mean 0.41% higher HbA1c level than nonusers when adjusted for insulin delivery method, income, and age (β, 0.41; 95% CI, 0.38-0.43).

    Discussion

    In the present survey study, the prevalence of cannabis use was 30% among adults with T1D. Cannabis use was associated with a higher risk for DKA in this population. Cannabinoids alter gut motility and cause hyperemesis, which may play a role in increased risk for DKA in T1D.4,6 A small sample size, single-center, and self-reported diabetes outcomes are limitations of the present study. The possibility of unmeasured confounders, such as access to health care, cannot be excluded. Further research is needed to confirm these findings and understand the effects and adverse consequences of cannabis use in patients with T1D.

    Back to top
    Article Information

    Accepted for Publication: August 3, 2018.

    Corresponding Author: Viral N. Shah, MD, Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, 1775 Aurora Ct, Room M20-1318, Aurora, CO 80045 (viral.shah@ucdenver.edu).

    Published Online: November 5, 2018. doi:10.1001/jamainternmed.2018.5142

    Author Contributions: Dr Shah had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Akturk, Camsari, Shah.

    Acquisition, analysis, or interpretation of data: Akturk, Taylor, Rewers, Kinney, Shah.

    Drafting of the manuscript: Akturk, Taylor, Camsari, Rewers, Shah.

    Critical revision of the manuscript for important intellectual content: Akturk, Rewers, Kinney, Shah.

    Statistical analysis: Taylor, Kinney, Shah.

    Administrative, technical, or material support: Rewers.

    Supervision: Kinney, Shah.

    Conflict of Interest Disclosures: Dr Shah reported receiving research support through the University of Colorado from Sanfo US, Dexcom Inc, Eyenuk Inc, and T1D Exchange clinic registry and consulting fees through the University of Colorado from Sanofi US and Dexcom Inc, all outside the submitted work. No other disclosures were reported.

    References
    1.
    Hasin  DS, Sarvet  AL, Cerdá  M,  et al.  US adult illicit cannabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013.  JAMA Psychiatry. 2017;74(6):579-588. doi:10.1001/jamapsychiatry.2017.0724PubMedGoogle ScholarCrossref
    2.
    Jadoon  KA, Ratcliffe  SH, Barrett  DA,  et al.  Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study.  Diabetes Care. 2016;39(10):1777-1786. doi:10.2337/dc16-0650PubMedGoogle ScholarCrossref
    3.
    Penner  EA, Buettner  H, Mittleman  MA.  The impact of marijuana use on glucose, insulin, and insulin resistance among US adults.  Am J Med. 2013;126(7):583-589. doi:10.1016/j.amjmed.2013.03.002PubMedGoogle ScholarCrossref
    4.
    Gallo  T, Shah  VN.  An unusual cause of recurrent diabetic ketoacidosis in type 1 diabetes.  Am J Med. 2016;129(8):e139-e140. doi:10.1016/j.amjmed.2016.02.033PubMedGoogle ScholarCrossref
    5.
    Adamson  SJ, Kay-Lambkin  FJ, Baker  AL,  et al.  An improved brief measure of cannabis misuse: the Cannabis Use Disorders Identification Test-Revised (CUDIT-R).  Drug Alcohol Depend. 2010;110(1-2):137-143. doi:10.1016/j.drugalcdep.2010.02.017PubMedGoogle ScholarCrossref
    6.
    Monte  AA, Zane  RD, Heard  KJ.  The implications of marijuana legalization in Colorado.  JAMA. 2015;313(3):241-242. doi:10.1001/jama.2014.17057PubMedGoogle ScholarCrossref
    ×