Body mass index is inversely associated with capillary ketones at the time of colonoscopy: Implications for SGLT2i use

Abstract

Objective Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been associated with diabetic ketoacidosis at the time of colonoscopy. This study aimed to identify factors associated with ketone concentrations in SGLT2i‐treated type 2 diabetes compared with non‐SGLT2i‐treated diabetes, and those with impaired fasting glycaemia (IFG) and normoglycaemia. Design Cross‐sectional, multicentre, observational study June–December 2020 in four Australian tertiary hospitals. Participants Capillary glucose and ketones were measured in people undergoing colonoscopy: 37 SGLT2i‐treated and 105 non‐SGLT2i‐treated type 2 diabetes, 65 IFG and 151 normoglycaemia. Measurements Body mass index (BMI), age, glucose, fasting duration and where relevant, HbA1c and time since last SGLT2i dose. Results In SGLT2i‐treated diabetes, BMI (ρ = −0.43 [95% confidence interval: −0.67, −0.11]) and duration since last SGLT2i dose (ρ = −0.33 [−0.60, 0.00]) correlated negatively with increasing ketones, but there was no correlation with fasting duration. In non‐SGLT2i‐treated diabetes, BMI correlated negatively (ρ = −0.24 [−0.42, −0.05]) and fasting duration positively (ρ = 0.26 [0.07, 0.43]) with ketones. In IFG participants, only fasting duration correlated with ketones (ρ = 0.28 [0.03, 0.49]). In normoglycaemic participants, there were negative correlations with BMI (ρ = −0.20 [−0.35, −0.04]) and fasting glucose (ρ = −0.31 [−0.45, −0.15]) and positive correlations with fasting duration (ρ = 0.20 [0.04, 0.35]) and age (ρ = 0.19 [0.03, 0.34]). Multiple regression analysis of the entire cohort showed BMI, age and fasting glucose remained independently associated with ketones, but in SGLT2i‐treated participants only BMI remained independently associated. Conclusions In SGLT2i‐treated diabetes, lower BMI was a novel risk factor for higher ketones precolonoscopy. Pending larger confirmatory studies, extra vigilance for ketoacidosis is warranted in these people.

Letter to the Editor: Response to Hamblin et al body mass index is inversely associated with capillary ketones at the time of colonoscopy: Implications for SGLT2i use

“…The correlation with insulin therapy was also observed in the subgroup taking and not taking SGLT2i. In contrast to the data presented by Hamblin et al, 1 there was no relationship between BMI and ketone peak in any group (Table 1) when accounting for the use of insulin.…”

“…Prompted by this observation, we performed a similar retrospective multivariate analysis in 94 SGLT2i treated individuals and 484 individuals with T2D not treated with SGLT2i who underwent a colonoscopy between 2019 and 2020 at the Queen Elizabeth Hospital in South Australia. The larger sample size enabled us to perform a sub‐analysis directly assessing the factors identified by Hamblin et al 1 and those identified by our own regression analysis and compare these factors in individuals who developed clinically significant ketosis (ketones >1.0 mmol/L) and those who did not 2 . In the SGLT2i treated individuals, we observed 17 cases of clinically significant ketosis (>1.0 mmol/L) equating to an incidence of 18%.…”

“…Insulin status was considered a binary outcome as information on dose was not available. Multivariate linear regression was performed to confirm the observation of Hamblin et al 1 regarding peak ketone concentration and associated with age, BMI and insulin status in both SGLT2i treated and nontreated individuals. To extend the clinical relevance of our data, we also conducted a retrospective case‐control study comparing the age, gender, BMI, HbA1c, American Society of Anesthesiologists Score, duration of SGLT2i held and insulin treatment status in SGLT2i treated individuals who developed clinically significant ketosis and those that did not.…”

“…This assumption may be predicated on the small sample size of the study, with only six individuals being noted to have ketones >0.7 mmol/L and only two individual >1.0 mmol/L. Correctly, Hamblin et al 1 conclude that larger trials examining ketosis in the colonoscopy population are required to support this hypothesis. Prompted by this observation, we performed a similar retrospective multivariate analysis in 94 SGLT2i treated individuals and 484 individuals with T2D not treated with SGLT2i who underwent a colonoscopy between 2019 and 2020 at the Queen Elizabeth Hospital in South Australia.…”

“…Hamblin et al 1 in their recent publication examine various associations with ketosis in the colonoscopy population. They make the novel observation that in this high‐risk population for SGLT2 inhibitor (SGLT2i) induced ketoacidosis that there is an inverse association between body mass index (BMI) and finger prick ketone measurement in 37 SGLT2i treated individuals and 105 individuals with type 2 diabetes (T2D) undergoing colonoscopy.…”