Diabetic Ketoacidosis or Cannabis Related Hyperglycemic Ketosis in patient with Type 1 Diabetes

A retrograde cohort study suggests that metabolic and acid base parameters may be useful in differentiating typical diabetic ketoacidosis DKA from Hyperglycemic Ketoacidosis related to cannabis hyperemesis syndrome in patients with type 1 Diabetes

After the legalization of cannabis in Colorado and increasing its use among patients with type 1 diabetes, emergency visits have been increased. The challenge is distinguishing between typical diabetic ketoacidosis and hyperglycemic ketosis in cannabis users with type 1 diabetes. The latter is related to cannabis hyperemesis syndrome characterized by morning nausea and severe vomiting that results in ketosis, followed by hyperglycemia. In contrast, in typical diabetic ketoacidosis, hyperglycemia would be initially developed, followed by ketoacidosis in response to infection, medication omission, or any other precipitating factor.

The study compared the metabolic and acid-base parameters of cannabis users and non-users who have visits to the emergency department ED with symptoms of DKA. Two physicians have analyzed electronic medical records data from 68 adult patients with type 1 diabetes followed at the Barbara Davis Center for Diabetes. Patients were seen in the ED with a DKA diagnosis between January 2016 and January 2021. Patients should meet the following criteria (based on venous blood glucose >250 mg/dL, anion gap >10, ketones as determined by serum b-hydroxybutyrate (BHB) ≥ 0.6 mmol/L and have available urine toxicology screening test report at admission. Investigators excluded patients without a cannabis urine drug test, pregnancy, measurable serum alcohol (if tested), and positive urine ketones without a serum BHB ≥ 0.6 mmol/L.

Hyperglycemic ketoacidosis related to cannabis hyperemesis HK-CHS was defined as a venous pH ≥ 7.4 with serum bicarbonate ≥15 mmol/L. Then investigators compared the percentage of HK-CHS episodes in patients with a urine test result positive for cannabis versus patients with a negative urine test result. The area under the receiver operating characteristic (ROC) curve and the sensitivity and specificity of cannabis use predicting HK-CHS presentation have been calculated using logistic regression analysis. All statistical analyses were conducted using SAS 9.4 software. A P value of <0.05 was considered statistically significant).

Researchers analyzed records of 68 patients with 172 ED events who have met inclusion criteria. Both cannabis users and cannabis non-users groups have elevated BHP while In mixed linear regression models with adjustment for age and sex; venous

pH was 7.09 ± 0.02 and 7.42 ± 0.01 (P < 0.0001), serum anion gap was 23.90 ± 0.71 and 20.94 ± 0.60 mmol/L (P = 0.01), and serum bicarbonate was 9.1 ± 0.71 and 19.20 ± 0.61 mmol/L (P < 0.0001) in cannabis non-users and cannabis users, respectively. In 96 % of events in cannabis users, venous pH ≥7.4 and serum bicarbonate ≥15 mmol/L accordingly; hyperglycemic ketosis was defined as HK-CHS if venous pH was ≥7.4 and serum bicarbonate was ≥15 mmol/L at the time of the ED visit. Using these cutoff values, the area under the ROC curve for positive cannabis urine test predicting HK-CHS was 98% (sensitivity of 97% and specificity of 95%). Similarly, when a sensitivity analysis was conducted using the BHB cutoff of ≥3.0 mmol/L, there were significant differences in pH and bicarbonate levels between cannabis users and non-users.

In conclusion, this study showed a statistically significant difference in metabolic and acid-base parameters between cannabis users and cannabis non-users admitted with DKA symptoms. Unusual higher pH ≥7.4 and bicarb ≥ 15 mmol/L with hyperglycemia (blood glucose ≥250 mg/dl) may suggest HK-CHS. Furthermore, the presence of metabolic alkalosis despite high anion gap ketosis in Type 1 diabetes cannabis users confirms the findings of a case series conducted in Australia that showed that diabetic ketosis presenting in cannabis users has a different metabolic and acid-base panel compared with cannabis non-users. Finally, treatment goals are to close the anion gap and decrease BHB with fluid replacement and insulin administration, clinical judgment cannabis users, and type 1 diabetes HK-CHS.

Practice Pearls

• With the legalization of cannabis, careful assessment of patients with type 1 diabetes admitted with hyperglycemia and DKA symptoms is essential to differentiate typical DKA from HK-CHS diagnosis.
• Depending only on arterial pH and bicarbonate can be misleading in cannabis users with type 1 diabetes. 
• Physicians should consider that the presence of metabolic alkalosis with high bicarb level with ketosis and DKA symptoms may indicate Cannabis use.

Refrences:

Akturk, Halis Kaan et al. “Differentiating Diabetic Ketoacidosis and Hyperglycemic Ketosis Due to Cannabis Hyperemesis Syndrome in Adults With Type 1 Diabetes.” Diabetes care, dc211730. 8 Dec. 2021, doi:10.2337/dc21-1730

Hennessy, Annemarie. “Cannabis masks diabetic ketoacidosis.” BMJ case reports vol. 2011 bcr0220102716. 4 Oct. 2011, doi:10.1136/bcr.02.2010.2716

Kinney, Gregory L et al. “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 vol. 43,1 (2020): 247-249. doi:10.2337/dc19-0365

Hebatullah Abdelgawad, ITPD Student, Skaggs School of pharmacy, University of Colorado