Hospitalization of Patients With Diabetes Due to Ketoacidosis Before and After the Initiation of Sodium-Glucose Cotransporter-2 Inhibitors.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a rare side effect related to sodium-glucose cotransporter-2 inhibitors (SGLT2I). This study investigated the incidence of people with diabetes hospitalized because of DKA after the implementation of SGLT2I (2015-2019), compared with the pre-SGLT2I era. METHODS: In this retrospective cohort study, medical records of all adult patients hospitalized with a diagnosis of DKA in a tertiary referral center from 2011-2019 were reviewed. The incidence of DKA was compared between the periods 2011-2014 and 2015-2019. Demographic and clinical data of patients hospitalized with DKA as well as SGLT2I use were extracted. RESULTS: During 2011-2019, there were 186 hospitalizations because of DKA. The rate of hospitalization was stable during 2011-2019 at 0.22% ± 0.04% (95% CI, 0.18-0.25). The clinical characteristics of people hospitalized with DKA in 2011-2014 were similar to those of people hospitalized during 2015-2019. Only 7 people (6.1%) in the 2015-2019 cohort had SGLT2I-related DKA, and their clinical characteristics were similar to those of the rest of the cohort. CONCLUSIONS: The rate of hospitalizations because of DKA remained stable before and 5 years after SGLT2I were implemented for the treatment of type 2 diabetes mellitus. Larger, multi-institutional studies with longer follow-ups are needed to study the effect of SGLT2I on the rate of hospitalizations because of DKA among people with diabetes. Although DKA events associated with SGLT2I are rare, they should be strongly considered in the differential diagnosis of people treated with these medications.

Cardiorespiratory fitness and survival following cancer diagnosis.

AIMS: Data on the association of cardiorespiratory fitness with survival of cancer patients are limited. This study aimed to evaluate the association between midlife cardiorespiratory fitness and survival after a subsequent cancer diagnosis. METHODS: We evaluated 19,134 asymptomatic self-referred adults who were screened in preventive healthcare settings. All subjects were free of cardiovascular disease and cancer at baseline and completed a maximal exercise stress test. Fitness was categorised into age-specific and sex-specific quintiles according to the treadmill time and dichotomised to low (quintiles 1-2) and high fitness groups. RESULTS: The mean age was 50 ± 8 years and 72% were men. During a median follow-up of 13 years (interquartile range 7-16) 517 (3%) died. Overall, 1455 (7.6%) subjects developed cancer with a median time to cancer diagnosis of 6.4 years (interquartile range 3-10). Death from the time of cancer diagnosis was significantly lower among the high fitness group (Plog rank = 0.03). Time-dependent analysis showed that subjects who developed cancer during follow-up were more likely to die (P < 0.001). The association of cancer with survival was fitness dependent such that in the lower fitness group cancer was associated with a higher risk of death, whereas among the high fitness group the risk of death was lower (hazard ratio 20 vs. 15; Pfor interaction = 0.047). The effect modification persisted after applying a 4-year blanking period between fitness assessment and cancer diagnosis (Pfor interaction = 0.003). CONCLUSION: Higher midlife cardiorespiratory fitness is associated with better survival among cancer patients. Our findings support fitness assessment in preventive healthcare settings.

Cardiorespiratory Fitness Is an Independent Predictor of Cardiovascular Morbidity and Mortality and Improves Accuracy of Prediction Models.

BACKGROUND: Although cardiorespiratory fitness (CRF) is a strong independent predictor of adverse cardiovascular outcomes, it is not considered as a risk enhancer by current guidelines. METHODS: We evaluated asymptomatic self-referred adults aged 40 to 79 years of age, free of cardiovascular disease at baseline, who were screened annually and completed baseline exercise stress test. Baseline CRF was dichotomized into 2 groups: low (metabolic equivalents < 8) and high. The primary endpoint was the composite of death, nonfatal acute coronary syndrome, and stroke after excluding subjects diagnosed with metastatic cancer during follow-up. RESULTS: Study population included 15,445 subjects with median age of 49 years (interquartile range: 44-55). During median follow-up of 8 years 1362 (9%) subjects developed the study endpoint. Kaplan-Meier survival analysis showed that both fitness and atherosclerotic cardiovascular disease (ASCVD) were associated with developing of the study endpoint (P < 0.001 for both). Cox regression model with adjustment for ASCVD risk consistently showed that lower fitness was associated with a significant 23% higher risk to develop the study endpoint (P = 0.001). Continuous net reclassification improvement analysis showed an overall improvement of 11.4% (95% confidence interval, 8%-14.6%; P value < 0.001) in the accuracy of classification when fitness was added to the ASCVD model. CONCLUSIONS: Low CRF is a strong independent predictor of the cardiovascular morbidity and mortality in asymptomatic adults. Addition of fitness to the pooled cohort ASCVD risk significantly improves the accuracy of the model.