[Normoglycaemic ketoacidosis induced by the use of sglt2 inhibitors : impact of intense physiological stress and fasting]. / Acidocétose normoglycémique induite par la prise de gliflozines en cas de stress physiologique intense et de jeûne.

Ketoacidosis is a serious complication of diabetes that only occurs in cases of absolute or severe relative insulin deficiency. This condition is rare in type 2 diabetes. The use of gliflozin during intense physiological stress associated with fasting can lead to the development of ketoacidosis without severe hyperglycaemia. The diagnosis of this normoglycaemic or euglycaemic diabetic ketoacidosis in the context of type 2 diabetes may be challenging. The treatment of metabolic acidosis cannot rely solely on symptomatic measures such as bicarbonate infusion. The demonstration of metabolic acidosis necessitates the search for an etiological diagnosis. The calculation of the anion gap is the cornerstone of the pathophysiological diagnosis of metabolic acidosis. In the context of diabetes, the occurrence of metabolic acidosis of unknown etiology requires its calculation and systematic measurement of ketones, even in the absence of severe hyperglycaemia. Only the etiological treatment of diabetic ketoacidosis, which is insulin therapy, allows for the lasting restoration of acid-base balance. Normoglycaemic ketoacidosis induced by the use of gliflozin during intense physiological stress associated with fasting should therefore be a recognized situation by healthcare providers.

L'acidocétose est une complication grave du diabète qui ne survient qu'en cas de déficit en insuline, absolu ou relatif sévère. Cette condition est rare dans le diabète de type 2. La prise de gliflozines en cas de stress physiologique intense, notamment associé à un jeûne, peut induire la survenue d'une acidocétose sans hyperglycémie sévère. Cette acidocétose diabétique dite normoglycémique ou euglycémique dans le cadre d'un diabète de type 2 est source d'errance diagnostique. Le traitement d'une acidose métabolique ne peut pas se satisfaire de l'instauration de mesures symptomatiques comme la perfusion de bicarbonates. La démonstration d'une acidose métabolique impose la recherche d'un diagnostic étiologique. Le calcul du trou anionique est la pierre angulaire du diagnostic physiopathologique d'une acidose métabolique. Dans le cadre du diabète, la survenue d'une acidose métabolique d'étiologie inconnue impose son calcul et le dosage systématique de la cétonémie, même en l'absence d'hyperglycémie sévère, a fortiori en cas de traitement par gliflozine. Seul le traitement étiologique d'une acidocétose diabétique, l'insulinothérapie, permet la restitution durable de l'équilibre acido-basique. L'acidocétose normoglycémique induite par la prise de gliflozines en cas de stress physiologique intense associé à un jeûne doit donc être une situation connue.

Diabetic ketosis vs ketoacidosis as initial presentation of pediatric type 1 diabetes mellitus. Associated features and rate of progression during the first two years after diagnosis.

AIMS: In this study we described the clinical and laboratory features of children presented with diabetic ketosis or diabetic ketoacidosis at diagnosis of type 1 diabetes (T1DM) and evaluated its course up to 2 years after initial diagnosis to investigate the progression rate of T1DM in both groups. METHODS: This was a prospective longitudinal cohort study that included 59 children and adolescents presented with either diabetic ketosis (DK) (n = 27) or diabetic ketoacidosis (DKA) (n = 32) at their first diagnosis with T1DM. RESULTS: Apart from the metabolic state of presentation at diagnosis, differences in the other basic clinical and laboratory features of both DK and DKA were not statistically significant (age, BMI, pre- diagnosis symptomatic period, HbA1c, multiplicity of autoantibodies positivity, fasting insulin, and total IgG levels), except from the C-peptide and IgA levels which were lower in DKA (p < 0.05). Regarding family history, only the DK group had individuals with a parent diagnosed with T1DM (p = 0.001). During follow-up there was no difference in the levels of HbA1c, basal insulin dose, and insulin/carbohydrate ratio between the DK and DKA group at 3,6,12 and 24 months' time points. CONCLUSIONS: The severity of presentation of T1DM (DK or DKA) is not associated to the rate of progression of the disease course after diagnosis.

Bacteremia due to Serratia rubidaea in intensive care unit: a case series.

INTRODUCTION: Bacteremia caused by Serratia rubidaea is seldom mentioned in comparison with other Enterobacteriaceae species. It primarily affects immunocompromised patients undergoing invasive procedures. Furthermore, the incidence, clinical features, and microbiological profile of this pathogen in the intensive care unit are rarely described. CASE PRESENTATION: We present four North African case studies of bacteremia in four young female patients admitted to the intensive care unit for ketoacidosis with a history of diabetes mellitus. All four patients developed catheter-related infections complicated by deep vein thrombosis. The catheter site was femoral in all cases, and the main clinical manifestation was poorly tolerated fever. The pathogen was isolated in multiple peripheral blood cultures (> 4) for each patient, showing a similar profile in all cases: resistance to third-generation cephalosporins and sensitivity to aminoglycosides, piperacillin, fluoroquinolones, and folate-pathway inhibitors. Targeted treatment consisted of a combination of ciprofloxacin 400 mg twice per day and trimethoprim/sulfamethoxazole 400/80 mg thrice per day for all four cases. However, in one case, this regimen was switched to amikacin due to adverse effects. The outcomes were favorable in the majority of cases. The patients described in this study were 21, 66, 22, and 27-year-old North African women. CONCLUSION: Most of the reported cases shared common risk factors and clinical aspects. Notably, a case of thrombosis complicating a catheter infection caused by Serratia rubidaea has not been previously reported in the literature. Furthermore, this bloodstream infection typically affects deeply immunocompromised patients. However, our four cases, admitted to the intensive care unit for ketoacidosis, only had a history of diabetes mellitus.

[Reversible bilateral blindness associated with alcoholic ketoacidosis: a case report].

A 51-year-old male with a history of chronic alcoholism presented to the emergency department with an abrupt onset of complete bilateral blindness lasting for one hour. Funduscopic examination yielded unremarkable findings. Systemic evaluations revealed the presence of severe ketoacidosis. The patient spontaneously regained light perception after experiencing total blindness for 3 hours; however, he subsequently developed hypothermia and entered a state of shock. Following treatment with sodium bicarbonate and aggressive fluid resuscitation, his condition stabilized, and there was a rapid improvement in his visual acuity. The diagnosis of alcoholic ketoacidosis was established based on the patient's history of chronic alcohol abuse, physical examination findings, and blood analysis results.

Treatment of a Severe Form of Euglycemic Ketoacidosis in a Patient Treated with SGLT-2 Inhibitors with the Aid of Somatostatin.

Currently, the use of SGLT2 inhibitors is becoming more widespread, both for their role in controlling diabetes, and for their pleiotropic effects on glomerular hyperfiltration and heart failure. Along with their positive effects, these drugs can lead to various complications, the most severe being euglycemic ketoacidosis. The clinical case we have reported precisely describes this potentially serious complication which occurred in a 47-year-old patient who had been on SGLT2 inhibitor therapy for 5 years. In the resolution of this case we used, in addition to standard therapy, the continuous infusion of somatostatin, resulting in a rapid resolution of ketoacidosis and an improvement in the clinical condition.

Clinical characteristics of patients with early-onset diabetes mellitus: a single-center retrospective study.

BACKGROUND: The prevalence of diabetes mellitus (DM) is dramatically increasing around the world, and patients are getting younger with changes in living standards and lifestyle. This study summarized and analyzed the clinical characteristics of different types of newly diagnosed diabetes mellitus patients with an onset age between 18 and 40 years to provide clinical evidence for the early diagnosis and treatment of diabetes, reduce short-term and long-term complications and offer scientific and personalized management strategies. METHODS: A total of 655 patients newly diagnosed with early-onset diabetes mellitus in the Department of Endocrinology, the First Medical Center of PLA General Hospital from January 2012 to December 2022 were retrospectively enrolled in this study, with an onset age of 18-40 years. Their clinical data were collected and investigated. All patients were divided into two groups according to whether they presented with diabetic microangiopathy. Similarly, patients with early-onset type-2 diabetes were grouped in accordance with whether they had ketosis at the time of diagnosis. Binary logistic regression analysis was performed to analyze risk factors, and receiver-operating characteristic (ROC) analysis was used to explore the predictive value of significant risk factors. RESULTS: The findings were as follows: (1) Of 655 enrolled patients, 477 (72.8%) were male and 178 (27.1%) were female, with a mean age of onset of was 29.73 years ± 0.24 SD. (2) The prevalence of early-onset diabetes was gradually increasing. Type-2 diabetes was the most common type of early-onset diabetes (491, 75.0%). The ages of onset of early-onset type-1 diabetes, type-2 diabetes and LADA were mainly 18-24 years, 25-40 years and 33-40 years, respectively. (3) Initial clinical manifestations of early-onset diabetes were classic diabetes symptoms (361, 55.1%), followed by elevated blood glucose detected through medical examination (207, 31.6%). (4) Binary logistic regression analysis suggested that high serum uric acid (UA), a high urinary albumin-to-creatinine ratio (UACR) and diabetic peripheral neuropathy (DPN) were risk factors for microangiopathy in early-onset diabetes patients (P < 0.05). The area under the curve (AUC) on ROC analysis of the combination of UA, UACR and DPN was 0.848, 95% CI was 0.818 ~ 0.875, sensitivity was 73.8% and specificity was 85.9%, which had higher predictive value than those of UA, UACR and DPN separately. (5) Weight loss, high glycosylated hemoglobin (HbA1c) and young onset age were risk factors for ketosis in patients with early-onset type-2 diabetes (P < 0.05). CONCLUSION: (1) Men were more likely to have early-onset diabetes than women. (2) Early-onset diabetes patients with high serum uric acid levels, high UACRs and peripheral neuropathy were prone to microangiopathy. Comprehensive evaluation of these risk factors could have higher predictive value in the prediction, diagnosis and treatment of microvascular lesions. (3) Patients with weight loss at onset, high HbA1c and young onset age were more likely to develop ketosis. Attention should be given to the metabolic disorders of these patients.

Ketosis-prone Diabetes and Hypogonadism: A New Clinical Association to be Aware of ?

BACKGROUND: Ketosis-prone diabetes (KPD) is an emerging entity, sharing features of both type 1 diabetes mellitus and type 2 diabetes mellitus. Patients with KPD usually present with diabetic ketoacidosis without the classic phenotype of autoimmune type 1 diabetes. In most cases, they are Afro-American adults, who require insulin therapy for the management of acute decompensation, then usually encountering insulin-free remission for prolonged periods of time with diet or with non-insulin agents. Meanwhile, hypogonadism is a known condition that could be associated with higher risk of developing both type 1 and type 2 diabetes and could be a risk factor for decompensated diabetes. The association of KPD and hypogonadism is reported for the first time in literature. CASE PRESENTATION: Here we report two peculiar cases of young African patients, affected by KPD and hypergonadotropic hypogonadism, respectively Klinefelter's syndrome and primary ovarian failure. Both patients were treated promptly for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. After the correct clinical evaluation, oral antidiabetic drugs were added. CONCLUSION: KPD remains an under-recognized and under-diagnosed type of diabetes. As hypogonadism is strongly linked to dysmetabolic disorders, the evaluation of sex hormones should be performed at the onset of diabetes. Further studies should investigate the hypothalamic-pituitary-gonadal axis and its role in the development of KDP and its manifestations and complications.

Type 1 diabetes in low and middle-income countries - Tanzania a streak of hope.

Introduction: In several of the Low and Middle Income countries , many patients with Type 1 diabetes (T1D) are most probably not diagnosed at all which may contribute to their low incidence. As an example of a country with low income and poor resources, we have chosen to study T1D in children/young people in Tanzania. Methods: Analyses of casebooks and statistics at several Tanzanian hospitals treating young patients with insulin dependent diabetes, usually Type 1 diabetes, and collection of information from different organisations such a Tanzanian Diabetes Association, Life for a Child, Changing Diabetes in Children and World Diabetes Foundation. Results: The incidence in several areas is low. However, a lot of data are often missing at studied clinics and therefore the incidence might be higher, and with increased awareness in recent years the number of patients has increased many-folds. Most patients present with typical symptoms and signs of T1D, and a high proportion with plausible ketoacidosis , although this proportion has decreased from about 90% to about 40% in recent decades. Many patients have poor blood glucose control, and complications often develop already after short diabetes duration. In recent years resources have increased, awareness has increased and diabetes clinics started where staff has got training. Conclusions: There are problems with diabetes care in Tanzania but several facts give hope for the future.

COVID-19 associated ketosis and diabetic ketoacidosis: A rapid review.

SARS-CoV-2 infection could disrupt the endocrine system directly or indirectly, which could result in endocrine dysfunction and glycaemic dysregulation, triggering transient or persistent diabetes mellitus. The literature on the complex relationship between COVID-19 and endocrine dysfunctions is still evolving and remains incompletely understood. Thus, we conducted a review on all literature to date involving COVID-19 associated ketosis or diabetic ketoacidosis (DKA). In total, 27 publications were included and analysed quantitatively and qualitatively. Studies included patients with DKA with existing or new onset diabetes. While the number of case and cohort studies was limited, DKA in the setting of COVID-19 seemed to increase risk of death, particularly in patients with new onset diabetes. Future studies with more specific variables and larger sample sizes are needed to draw better conclusions.

Sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reports.

Although the recommended preoperative cessation period for sodium-glucose cotransporter 2 inhibitors (SGLT2is) changed in 2020 (from 24 h to 3-4 days preoperatively) to reduce the risk of SGLT2i-associated perioperative ketoacidosis (SAPKA), the validity of the new recommendation has not been verified. Using case reports, we assessed the new recommendation effectiveness and extrapolated precipitating factors for SAPKA. We searched electronic databases up to June 1, 2022 to assess SAPKA (blood pH < 7.3 and blood or urine ketone positivity within 30 days postoperatively in patients taking SGLT2i). We included 76 publications with 99 cases. The preoperative SGLT2i cessation duration was reported for 59 patients (59.6%). In all cases with available cessation periods, the SGLT2is were interrupted < 3 days preoperatively. No SAPKA cases with > 2-day preoperative cessation periods were found. Many case reports lack important information for estimating precipitating factors, including preoperative SGLT2i cessation period, body mass index, baseline hemoglobin A1c level, details of perioperative fluid management, and type of anesthesia. Our study suggested that preoperative SGLT2i cessation for at least 3 days could prevent SAPKA. Large prospective epidemiologic studies are needed to identify risk factors for SAPKA.

Diabetic ketoacidosis with SGLT2 inhibitor use - a patient series. / Diabetisk ketoacidose ved bruk av SGLT2-hemmer ­ en pasientserie.

BACKGROUND: Inhibitors of sodium glucose cotransporter 2 (SGLT2 inhibitors) are increasingly being used to treat type 2 diabetes. Results from previous studies suggest a rising incidence of diabetic ketoacidosis with the use of this medication. MATERIAL AND METHOD: We performed a diagnosis search in the electronic patient records at Haukeland University Hospital for the period 1 January 2013-31 May 2021 with the aim of identifying patients with diabetic ketoacidosis who used SGLT2 inhibitors. A total of 806 patient records were reviewed. RESULTS: Twenty-one patients were identified. Thirteen had severe ketoacidosis, and ten had normal blood glucose levels. Probable triggering causes were found in 10 of the 21, with recent surgery being the most common (n = 6). Three of the patients were not tested for ketones, and 9 were not tested for antibodies to rule out type 1 diabetes. INTERPRETATION: The study showed that severe ketoacidosis occurs in patients with type 2 diabetes using SGLT2 inhibitors. It is important to be aware of this risk and the fact that ketoacidosis can occur without hyperglycaemia. Arterial blood gas and ketone tests must be performed to make the diagnosis.

Thoracoscopic esophagectomy for stenosis of thoracic esophagus due to acute esophageal necrosis associated with alcoholic ketoacidosis.

Acute esophageal necrosis (AEN) is a rare disease characterized by the appearance of diffuse black mucosa on upper gastrointestinal endoscopy; the condition often progresses to esophageal stenosis in the chronic phase. A 70-year-old man was admitted to a neighborhood hospital with the diagnosis of alcoholic ketoacidosis and an upper gastrointestinal endoscopy performed to investigate the symptom of esophageal tightness revealed AEN. The patient developed esophageal stenosis with scarring in the chronic phase and was referred to our hospital for surgery 6 months after the diagnosis of AEN. We performed thoracoscopic esophagectomy with the patient in the prone position. Although the esophagus was thickened and strong adhesions were present around the esophagus due to inflammation, we were able to complete the surgical procedure thoracoscopically. In patients presenting with benign esophageal stenosis developing after AEN, thoracoscopic esophagectomy may be a useful treatment option, even in the presence of severe fibrosis.

Significant ketoacidosis at autopsy: a single-centre systematic review.

AIM: To examine the value of vitreous beta-hydroxybutyrate and serum acetone in the investigation of sudden unexpected death. METHODS: Coroners' autopsy reports from a provincial UK city, with a population of approximately 900 000, over a 24-month period with significant ketoacidosis were studied. Demographic features, medical history, anatomical and histological findings, and biochemical parameters, including renal function, vitreous glucose, serum and vitreous alcohol, were analysed. RESULTS: Forty-two cases (28 males and 14 females) were identified; 55% had a history of alcohol and/or substance misuse, and mental health problems, particularly depression and anxiety, and 16% were diabetic. In all, 50% of subjects had alcoholic ketoacidosis (AKA), 19% had diabetic ketoacidosis (DKA) and 12% had a history of both diabetes and alcohol abuse. In 19% of cases, an exact cause of ketoacidosis was established. In AKA, the subjects typically had low vitreous glucose and low or undetected blood alcohol levels. All of the subjects with raised vitreous glucose levels had DKA. CONCLUSION: Ketoacidosis is relatively common and should be considered as a cause of sudden death, especially in alcoholic patients and patients with diabetes with no clear cause of death at autopsy.

Epileptic seizures during Non-Ketotic Hyperglycemia (NKH) in French Guiana: A retrospective study.

Introduction: Epileptic seizures during non-ketotic hyperglycemia (NKH) represent a rare complication of uncontrolled diabetes mellitus. The definition associates a blood sugar level > 200mg/dL (11mmol/L), hyperosmolality, absence of ketosis, dehydration and seizure control after normalization of blood sugar levels. Material and methods: This retrospective observational study included patients hospitalized for epileptic seizures and NKH in the Cayenne Hospital Center between January 2010 and June 2020. The clinical, biological, and radiological results were collected. Results: 18 out of 228 (7.9%) patients with both diabetes and epileptic seizures had NKH. The mean age of the 12 women and 6 men was 64.8 years. In 8 patients, brain imaging did not show acute lesions and the seizures disappeared with control of hyperglycemia by hydration and insulin. In 6 patients, the seizures revealed a stroke, hemorrhagic in 4 cases, ischemic in 2 cases. 4 patients had a seizure in a context of known vascular epilepsy. The epileptic seizures were mainly focal seizures with motor symptoms that could be repeated, focal to bilateral tonic-clonic or focal status. Conclusion: Seizures in NKH are symptomatic of an acute brain lesion or vascular epilepsy more than 1 in 2 times. However, isolated NKH can cause seizures with a suggestive brain MRI.

Anti-programmed Cell Death Protein-1 Therapy in Intrahepatic Cholangiocarcinoma Induced Type 1 Diabetes: A Case Report and Literature Review.

Immune checkpoint inhibitors, widely used in the treatment of malignancies, can improve the prognosis of patients, while it also can induce various immune-related adverse events, and type 1 diabetes induced by anti-programmed cell death protein-1 is a rare but severe complication. Here we reported a case of type 1 diabetes induced by anti-PD-1 which was to treat intrahepatic cholangiocarcinoma. The case was a 61-year-old female who developed diabetes and ketoacidosis symptoms at the 16th week after anti-PD-1 therapy. Her blood glucose was 30.32 mmol/L, HBA1c was 8.10%, and C-peptide was <0.10 ng/ml. The patient was diagnosed as fulminant type 1 diabetes mellitus complicated with ketoacidosis induced by anti-PD-1, and was treated with massive fluid rehydration, intravenous infusion of insulin and correction of acid-base electrolyte disorder. Hepatectomy was performed after stabilization, and the patient was treated with long-term insulin. Through the case report and literature review, this study aims to improve oncologists' understanding of anti-PD-1 induced type 1 diabetes, so as to make early diagnosis and treatment of the complications and ensure medical safety.

[About the safety profile of SGLT2 inhibitors]. / À propos de la sécurité d'emploi des inhibiteurs des SGLT2 (gliflozines).

Since their launch, sodium-glucose cotransporter type 2 inhibitors (SGLT2is) were suspected to be associated with various adverse events. They contributed to delay, as in France, or to restrict the use of this new pharmacological class in clinical practice, despite remarkable results reported in large cardiovascular or renal clinical trials. This article is devoted to three major adverse events that were imputed to SGLT2is : lower-limb extremity amputations, euglycaemic ketoacidosis and acute kidney injuries. In contrast to pharmacovigilance reports that raised suspicion, analysis of all data from the literature, either placebo-controlled trials or retrospective observational cohort studies, led to rather reassuring conclusions. The incidence of amputations does not appear to be increased while cases of acute kidney injury are reduced instead of increased as suspected earlier. Ketoacidosis events are almost doubled with SGLT2is versus comparators, yet their incidence remains extremely low among patients with type 2 diabetes. Of note, this potentially severe complication contributes to the denial of marketing authorization and reimbursement of SGLT2is in the population with type 1 diabetes.

Depuis leur mise sur le marché, les inhibiteurs des cotransporteurs sodium-glucose de type 2 (iSGLT2) ont été incriminés dans diverses manifestations indésirables. Celles-ci ont contribué à retarder, comme en France, ou à limiter la prescription de cette nouvelle classe pharmacologique en pratique clinique, malgré les résultats remarquables rapportés dans de grands essais à visée cardiovasculaire ou rénale. Cet article fait le point sur trois effets secondaires délétères importants imputés aux iSGLT2 : les amputations des extrémités des membres inférieurs, les acidocétoses dites euglycémiques et les insuffisances rénales aiguës. Malgré des données de pharmacovigilance qui avaient soulevé la suspicion, l'analyse de l'ensemble des données de la littérature, que ce soit les essais prospectifs contrôlés versus placebo ou les études observationnelles rétrospectives de cohorte versus des comparateurs actifs, aboutit à des conclusions assez rassurantes. Les amputations ne semblent pas être augmentées tandis que les cas d'insuffisance rénale aiguë sont plutôt en diminution au lieu de présenter une incidence accrue. Les cas d'acidocétose sont environ doublés sous iSGLT2 par rapport aux comparateurs, mais leur incidence reste extrêmement basse chez les patients diabétiques de type 2. Rappelons, néanmoins, que c'est cette complication potentiellement grave qui a entraîné le refus d'autorisation de mise sur le marché et du remboursement des iSGLT2 dans la population diabétique de type 1.

Incidence of Type 1 diabetes and factors associated with presence and severity of ketoacidosis at onset in children.

BACKGROUND AND AIM: To assess the incidence of Type 1 Diabetes Mellitus (T1DM) during the period 2012-2017, the frequency and severity of ketoacidosis (DKA) at diabetes onset, and the factors associated with DKA in children and adolescents younger than 18 years old in the Abruzzo region, Italy. METHODS: All incident cases of T1DM (0-17 years old) diagnosed between January 2012 and December 2017 were included. Data about the patients were obtained from two independent sources; insulin prescriptions and medical records. Clinical data at diabetes onset, as well as demographic and non-demographic data, including center of first hospitalization, distance to regional reference center and number of pediatricians (per 1000 residents younger than 18 years) were collected and evaluated. RESULTS: During 2012-2017 period, 177 patients were diagnosed with T1DM. In 2012, T1DM incidence was 15.6 per 100,000/year; in 2013, 16.4 per 100,000/year; in 2014, 11.6 per 100,000/year; in 2015, 14.2 per 100,000/year; in 2016, 16.2 per 100,000/year and in 2017, 12.2 per 100,000/year. DKA was present in 29.3% of patients, 6.9% with severe DKA. The DKA presence was correlated to age (p<0.02), ethnicity (p<0.04), being transferred to a specialist center instead of being directly admitted to one (p<0.002) and the number of pediatricians in the population (p<0.01). The DKA severity was associated with the delay of transfer (p<0.04). CONCLUSIONS: Being admitted directly to a specialist center is very important and it could be expression of high alertness of pediatricians. Availability of well-trained pediatricians is necessary for the prevention of DKA. (www.actabiomedica.it).

Relationship of concomitant anti-diabetic drug administration with sodium-glucose co-transporter 2 inhibitor-related ketosis.

OBJECTIVE: The use of sodium-glucose co-transporter 2 inhibitors (SGLT2is) may be associated with ketoacidosis. Therefore, the associated risk factors should be identified. In particular, information regarding the effects of the co-administration of anti-diabetic drugs is lacking. METHODS: We performed a retrospective study of 68 consecutive patients with diabetes who were taking an SGLT2i and attending a single medical center. After a period of treatment (median 78 days), their circulating ketone concentrations were measured. The concomitant use of other anti-diabetic drugs was analyzed to identify independent risk factors associated with ketosis. RESULTS: Twenty-five participants were taking empagliflozin, 23 were taking dapagliflozin, and 20 were taking canagliflozin. During the treatment period, no ketoacidotic events were recorded and their mean circulating ketone concentrations at the end of the study period were similar (0.3 mmol/L in the empagliflozin group, 0.26 mmol/L in the dapagliflozin group, and 0.25 mmol/L in the canagliflozin group). After adjustment for the use of anti-diabetic drugs, pioglitazone was found to be independently associated with a risk of high circulating ketone concentration (B value: 0.361, 95% confidence interval: 0.181-0.541). CONCLUSION: SGLT2i-associated ketoacidosis was found to be infrequent, but the concomitant use of pioglitazone was associated with a higher risk of ketosis.

Increase in the Number of Pediatric New-Onset Diabetes and Diabetic Ketoacidosis Cases During the COVID-19 Pandemic.

OBJECTIVE: Infection with SARS-CoV-2 induces a proinflammatory state that causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA) in patients with known or new-onset diabetes. We examined the trends in new-onset diabetes and DKA prior to and following the onset of the COVID-19 pandemic. METHODS: This single-center retrospective observational study included pediatric patients (aged 0 to <18 years) hospitalized with new-onset type 1 diabetes or type 2 diabetes (T2D) before (March 1, 2018, to February 29, 2020) and after (March 1, 2020 to December 31, 2020) the pandemic onset. Demographic, anthropometrics, laboratory and clinical data, and outcomes were obtained. RESULTS: Among 615 children admitted with new-onset diabetes during the entire study period, 401 were admitted before the pandemic onset, and 214 were admitted after the pandemic onset. Children admitted with new-onset diabetes in the postpandemic period were significantly more likely to present with DKA (odds ratio, 1.76; 95% confidence interval, 1.24-2.52) than in the prepandemic phase. Children with DKA after the pandemic onset had higher lengths of hospitalization and were significantly more likely to experience severe DKA (odds ratio, 2.17; 95% confidence interval, 1.34-3.52). A higher proportion of children with DKA admitted to the pediatric intensive care unit required oxygen support after the pandemic onset than before the pandemic onset (8.85% vs 1.92%). Most cases of T2D with DKA occurred following the onset of the pandemic (62.5%). CONCLUSION: A significant increase in T2D cases occurred following the onset of the COVID-19 pandemic with a greater risk of DKA and severe ketoacidosis. Racial disparity was evident with a higher proportion of Black and American Indian children presenting with ketoacidosis following the pandemic onset.