SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment.

AIMS: To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS). METHODS: Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases. RESULTS: A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31 days, and canagliflozin had the longest onset time (96.5 days for euDKA and 75 days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA. CONCLUSIONS: Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.

Friedreich's Ataxia related Diabetes: Epidemiology and management practices.

AIMS: Friedreich's Ataxia (FRDA) is a progressive neuromuscular disorder typically caused by GAA triplet repeat expansions in both frataxin gene alleles. FRDA can be complicated by diabetes mellitus (DM). The objective of this study was to describe the prevalence of, risk factors for, and management practices of FRDA-related DM. METHODS: FACOMS, a prospective, multi-site natural history study, includes 1,104 individuals. Extracted data included the presence of DM and other co-morbidities, genetic diagnosis, and markers of disease severity. We performed detailed medical record review and a survey for the subset of individuals with FRDA-related DM followed at one FACOMS site, Children's Hospital of Philadelphia. RESULTS: FRDA-related DM was reported by 8.7% of individuals. Age, severe disease, and FRDA cardiac complications were positively associated with DM risk. FRDA-related DM was generally well-controlled, as reflected by HbA1c, though diabetic ketoacidosis did occur. Insulin is the mainstay of treatment (64-74% overall); in adults, metformin use was common and newer glucose-lowering agents were used rarely. CONCLUSIONS: Clinical factors identify individuals at increased risk for FRDA-related DM. Future studies should test strategies for FRDA-related DM screening and management, in particular the potential role for novel glucose-lowering therapies in preventing or delaying FRDA-related cardiac disease.

Comparing patient characteristics and outcomes in type 1 versus type 2 diabetes with diabetic ketoacidosis: a review and a propensity-matched nationwide analysis.

Diabetic ketoacidosis (DKA) is a known complication of patients with type 1 diabetes mellitus (T1DM), but less common in type 2 diabetes mellitus (T2DM). The aim of this study was to compare the outcomes of patients admitted to the hospital with DKA in T1DM versus T2DM. This was a population-based, retrospective, cohort study using data from the Nationwide Inpatient Sample. The group of patients hospitalized for DKA was divided based on a secondary diagnosis of either T1DM or T2DM. The primary outcome was inpatient mortality, and the secondary outcomes were rate of complications, length of hospital stay (LOS) and total hospital charge (THC). The inpatient mortality for DKA was 0.27% (650 patients). In T2DM, the adjusted OR (aOR) for mortality was 2.13 (95% CI 1.38 to 3.28, p=0.001) with adjusted increase in mean THC of $6035 (95% CI 4420 to 7652, p<0.001) and mean LOS of 0.5 day (95% CI 0.3 to 0.6, p<0.001) compared with T1DM. Patients with T2DM had significantly higher odds of having septic shock (aOR 2.02, 95% CI 1.160 to 3.524, p=0.013) compared with T1DM. T2DM was associated with higher inpatient mortality, septic shock and increase in healthcare utilization costs compared with T1DM.

Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers.

OBJECTIVE: We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites. METHOD: This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level. RESULTS: We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]). CONCLUSION: We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.

Complications of Serious Pediatric Conditions in the Emergency Department: Definitions, Prevalence, and Resource Utilization.

OBJECTIVES: To define and measure complications across a broad set of acute pediatric conditions in emergency departments using administrative data, and to assess the validity of these definitions by comparing resource utilization between children with and without complications. STUDY DESIGN: Using local consensus, we predefined complications for 16 acute conditions including appendicitis, diabetic ketoacidosis, ovarian torsion, stroke, testicular torsion, and 11 others. We studied patients under age 18 years using 3 data years from the Healthcare Cost and Utilization Project Statewide Databases of Maryland and New York. We measured complications by condition. Resource utilization was compared between patients with and without complications, including hospital length of stay, and charges. RESULTS: We analyzed 27 087 emergency department visits for a serious condition. The most common was appendicitis (n = 16 794), with 24.3% of cases complicated by 1 or more of perforation (24.1%), abscess drainage (2.8%), bowel resection (0.3%), or sepsis (0.9%). Sepsis had the highest mortality (5.0%). Children with complications had higher resource utilization: condition-specific length of stay was longer when complications were present, except ovarian and testicular torsion. Hospital charges were higher among children with complications (P < .05) for 15 of 16 conditions, with a difference in medians from $3108 (testicular torsion) to $13 7694 (stroke). CONCLUSIONS: Clinically meaningful complications were measurable and were associated with increased resource utilization. Complication rates determined using administrative data may be used to compare outcomes and improve healthcare delivery for children.

Pediatric diabetic ketoacidosis: an outpatient perspective on evaluation and management.

Diabetic ketoacidosis is a common, serious acute complication in children with diabetes mellitus. Diabetic ketoacidosis can accompany new-onset type 1 diabetes mellitus or it can occur with established type 1 diabetes mellitus during the increased demands of an acute illness or with decreased insulin delivery due to omitted doses or insulin pump failure. Additionally, diabetic ketoacidosis episodes in children with type 2 diabetes mellitus are being reported with greater frequency. Although the diagnosis is usually straightforward in a known diabetes patient with expected findings, a fair proportion of patients with new-onset diabetes present in diabetic ketoacidosis. The initial management of children with diabetic ketoacidosis frequently occurs in an emergency department. Physicians must be aware that diabetic ketoacidosis is an important consideration in the differential diagnosis of pediatric metabolic acidosis. This review will acquaint emergency medicine clinicians with the pathophysiology, treatment, and potential complications of this disorder.

Coagulation assessment in children with diabetic ketoacidosis.

OBJECTIVES: To assess potential hypercoagulability during diabetic ketoacidosis in children. DESIGN: A prospective, controlled pilot study. SETTING: University-affiliated pediatric critical care unit and emergency department in a tertiary care children's hospital. PATIENTS: Children (1-18 years) admitted with an episode of diabetic ketoacidosis and healthy children as controls. All patients with diabetic ketoacidosis managed according to a preestablished protocol. INTERVENTIONS: Thromboelastography was performed using citrated whole-blood samples drawn at the time of admission and upon biochemical and clinical resolution of diabetic ketoacidosis. Citrated whole-blood samples drawn from healthy nondiabetic children acted as control samples. MEASUREMENTS AND MAIN RESULTS: Fifteen patients (11.7 ± 4.1 years) in the diabetic ketoacidosis group and 20 patients (8.9 ± 4.5 years; p = 0.06) in the control group completed the study. Values for standard thromboelastography parameters (R and K time, α angle, maximum amplitude, coagulation index, and Ly30) in the diabetic ketoacidosis group, both on admission and resolution, were within the control range; thromboelastography profiles of diabetic ketoacidosis patients on admission were not significantly different from profiles obtained upon diabetic ketoacidosis resolution. The mean α-angle was significantly higher in known diabetic patients compared with newly diagnosed diabetics on admission; however, it still remained within the control normal range. CONCLUSIONS: Thromboelastographic assay results do not reflect a hypercoagulable state in this group of children with diabetic ketoacidosis. Further investigation is required to examine the potential role of injured endothelium in the suspected hypercoagulability during diabetic ketoacidosis.

Trends in hospitalization for diabetic ketoacidosis in diabetic patients in Taiwan: analysis of national claims data, 1997-2005.

BACKGROUND/PURPOSE: Diabetic ketoacidosis (DKA) is a fatal complication of diabetes, and is strongly related to the quality of diabetes care. This study aimed to establish recent secular trends of incidence density (ID) of DKA in patients with diabetes in Taiwan and to explore the effects of age and sex on the risk of a DKA emergency. METHODS: Using the National Health Insurance claims data, we identified annual diabetic cohorts (around 650,000 diabetic patients annually) from 1997 to 2005, and searched for possible admissions due to DKA emergencies. We performed log-linear regression analysis to assess the trend in ID of DKA and to assess the independent effects of age and sex on the risk of DKA. RESULTS: Although the annual ID of DKA showed a slight but significant declining trend over the study period, from 6/1000 to 5/1000 person-years, the age/sex-specific analysis indicated that female patients aged ≤ 34 years showed a significantly increasing trend. Multivariate analysis revealed that calendar year and sex had significant but small independent effects on risk of DKA admission. In contrast, age was strongly associated with risk of DKA emergency. Compared with patients aged > 65 years, notably high adjusted rate ratios (ARRs) of DKA were observed in patients aged <15 years (ARR = 48.84) and 15-34 years (ARR =15.21). CONCLUSION: Although the overall ID of DKA linearly decreased between 1997 and 2005, significant rising trends were still observed in female diabetic patients aged < 35 years. More aggressive diabetic care programs aimed at young female patients should be considered to reduce this emergency and possibly fatal diabetic complications.

Glycemic parameters with multiple daily injections using insulin glargine versus insulin pump.

This study compared external insulin pump treatment using insulin lispro or insulin aspart with multiple daily injections (MDI; four or more injections per day) using insulin glargine and insulin lispro or insulin aspart. An electronic database was used to retrieve various parameters of glycemic control for 515 adult patients with type 1 diabetes. An insulin pump was used by 216 patients, and 299 patients were taking insulin glargine for at least 6 months. The mean age (approximately 33 years), duration of diabetes (approximately 16 years), and duration of treatment (approximately 12 months) were similar for both the pump and insulin glargine groups. The mean (+/-SEM) A1C values were significantly reduced in both groups from the baseline to the end of the study (7.7 +/- 0.1% to 7.5 +/- 0.1% for the pump group and 8.0 +/- 0.1% to 7.7 +/- 0.1% for the insulin glargine group, P< 0.001) with similar weight gain (P> 0.05) in both groups. The insulin glargine group significantly reduced basal insulin intake at follow-up. The premeal boluses were similar throughout the study for both groups. The subjects reporting severe hypoglycemic episodes were similar in the two groups; however, there were 12 cases of diabetic ketoacidosis reported in the pump group and none in the insulin glargine group. Patients with type 1 diabetes can achieve similar glycemic control using insulin glargine with premeal insulin lispro or by using an external infusion pump with insulin lispro or insulin aspart. However, costs and episodes of diabetic ketoacidosis are significantly higher for insulin pump users.

Resource utilization in treatment of diabetic ketoacidosis in adults.

This study defines determinants of cost of treatment of diabetic ketoacidosis. A chart review for 92 cases of ketoacidosis from 1988 to 1992 in 40 females and 25 males (age range 18 to 81) showed a length of stay of 5.7 +/- 4.9 d. Length of stay did not correlate with the level of nursing care or any other component of the initial order set. Length of stay was shorter in cases managed by diabetologists. Length of stay was inversely proportional to the interval from arrival to the first shot of intermediate or long-acting insulin. Length of stay was longer in subjects with a positive bacterial culture (mean, 9.1 d) and was longer in subjects who arrived in the evening. There was a female predominance in total and recurrent cases of ketoacidosis. Female patients received fewer educational sessions than males. The grade of acidosis affected the duration of acidemia, but the grade of acidosis, APACHE scores, and admission lab values did not correlate with length of stay. The use of an intensive care unit (ICU) included more testing and expense without uniform clear benefit. Optimal transition from intensive to routine management includes resumption of long-acting insulins as soon as possible. Optimization of hospital care and reduction of incidence of ketoacidosis in females would have a marked effect on health care costs.