Fulminant type 1 diabetes: Focusing on triggering factors.

Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic ß cells. Early diagnosis or prediction of FT1D is critical for the prevention or timely treatment of diabetes ketoacidosis, which can be life-threatening. Understanding its triggers or promoting factors plays an important role in the prevention and treatment of FT1D. In this review, we summarised the various triggering factors of FT1D, including susceptibility genes, immunological factors (cellular and humoural immunity), immune checkpoint inhibitor therapies, drug reactions with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome, pregnancy, viral infections, and vaccine inoculation. This review provides the basis for future research into the pathogenetic mechanisms that regulate FT1D development and progression to further improve the prognosis and clinical management of patients with FT1D.

Outcomes measured in studies assessing health systems interventions for type 1 diabetes management: A scoping review.

AIMS: Describe the outcomes reported in research on health systems interventions for type 1 diabetes management in comparison to the outcomes proposed by a core outcome set (COS) for this condition, an essential list of outcomes that studies should measure. METHODS: Systematic search of studies published between 2010 and 2021 reporting health systems interventions directed to improve the management of type 1 diabetes using PubMed, EMBASE and CENTRAL. Information on the outcomes was extracted and classified according to a COS: self-management, level of clinical engagement, perceived control over diabetes, diabetes-related quality of life, diabetes burden, diabetes ketoacidosis, severe hypoglycemia, and glycated hemoglobin (HbA1C). RESULTS: 187 studies were included. Most of the studies included either children (n = 82/187) or adults (n = 82/187) living with type 1 diabetes. The most common outcome measured was HbA1C (n = 149/187), followed by self-management (n = 105/187). While the least measured ones were diabetes ketoacidosis (n = 15/187), and clinical engagement (n = 0/187). None of the studies measured all the outcomes recommended in the COS. Additionally, different tools were found to be used in measuring the same outcome. CONCLUSIONS: This study provides a description of what researchers are measuring when assessing health systems interventions to improve type 1 diabetes management. In contrast to a COS, it was found that there is a predominance of clinical-based outcomes over patient-reported outcome measures.

Modifiable factors to prevent severe hypoglycaemic and diabetic ketoacidosis presentations in people with type 1 diabetes.

AIMS: In tackling rising diabetes-related emergencies, the need to understand and address emergency service usage by people with type 1 diabetes is vital. This review aimed to quantify current trends in presentations for type 1 diabetes-related emergencies and identify public health strategies that reduce the frequency of diabetes-related emergencies and improve glycaemic management. METHODS: Medline (OVID), Cochrane and CINAHL were searched for studies published between 2000 and 2023, focusing on people with type 1 diabetes, severe hypoglycaemia and/or diabetic ketoacidosis, and ambulance and/or emergency department usage. There were 1313 papers identified, with 37 publications meeting review criteria. RESULTS: The incidence of type 1 diabetes-related emergencies varied from 2.4 to 14.6% over one year for hypoglycaemic episodes, and between 0.07 and 11.8 events per 100 person-years for hyperglycaemic episodes. Notably, our findings revealed that ongoing diabetes education and the integration of diabetes technology, such as continuous glucose monitoring and insulin pump therapy, significantly reduced the incidence of these emergencies. However, socio-economic disparities posed barriers to accessing these technologies, subsequently shifting the cost to emergency healthcare and highlighting the need for governments to consider subsidising these technologies as part of preventative measures. CONCLUSIONS: Improving access to continuous glucose monitoring and insulin pump therapy, in combination with ongoing diabetes education focusing on symptom recognition and early management, will reduce the incidence of diabetes-related emergencies. Concurrent research assessing emergency healthcare usage patterns during the implementation of such measures is essential to ensure these are cost-effective.

Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts.

AIM: To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI) and genital infection (GI) among patients with type 2 diabetes initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND METHODS: In this large multinational, observational, new-user cohort study in UK, Danish and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014 and August 2019, were aged ≥18 years, and had ≥12 months' continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios, adjusted for propensity-score deciles, were calculated. RESULTS: In total, 64 599 empagliflozin initiators and 203 315 DPP-4 inhibitor initiators were included. There was an increased risk [pooled adjusted incidence rate ratios (95% confidence interval)] of DKA [2.19 (1.74-2.76)] and decreased risks of ALI [0.77 (0.50-1.19) in patients without predisposing conditions of liver disease; 0.70 (0.56-0.88) in all patients] and AKI [0.54 (0.41-0.73)]. In the UK data, there was an increased risk of GI [males: 4.04 (3.46-4.71); females: 3.24 (2.81-3.74)] and decreased risks of CKD [0.53 (0.43-0.65)] and severe complications of UTI [0.51 (0.37-0.72)]. The results were generally consistent in subgroup and sensitivity analyses. CONCLUSIONS: Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.

Risk of perioperative discontinuation of SGLT2 inhibitors.

When sodium-glucose cotransporter-2 (SGLT2) inhibitors were primarily prescribed for treatment of diabetes mellitus, guidelines recommended withholding SGLT2 inhibitors before surgery to mitigate the associated risk of ketoacidosis. However, currently, SGLT2 inhibitors are an established therapy for patients with heart failure, and there is evidence that withholding SGLT2 inhibitors can worsen these patients' cardiovascular risk profile. We present an updated risk-benefit analysis of withholding SGLT2 inhibitors before surgery, focusing on patients with heart failure and addressing the risk of ketoacidosis and its treatment in these patients. Clinicians should consider perioperative continuation of SGLT2 inhibitors when prescribed for treatment of heart failure.

Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.

OBJECTIVE: Hyperglycemia in patients with type 2 diabetes mellitus is frequently encountered in the hospital setting. The recent guidelines for the management of inpatient hyperglycemia have included the use of dipeptidyl peptidase 4 inhibitors as an alternative to standard insulin therapy in select patients. This raises the question of the inpatient use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), which have gained increasing popularity in the outpatient setting because of beneficial cardiovascular and renal outcomes. This article describes the risks associated with the use of SGLT2i for the management of inpatient hyperglycemia. METHODS: A literature review was performed using PubMed and Google Scholar for studies assessing the inpatient use of SGLT2i. Search terms included "SGLT2 inhibitors," "euglycemic DKA," "inpatient hyperglycemia," "DPP4 inhibitors," "hypovolemia," and "urinary tract infections." Studies not written in English were excluded. Forty-eight articles were included. RESULTS: Review of the literature showed significant safety concerns with the use of SGLT2i for the inpatient management of hyperglycemia. Hospitalized patients treated with SGLT2i were at increased risk of diabetic ketoacidosis, euglycemic diabetic ketoacidosis, hypovolemia, and urinary tract infections. When compared head-to-head, SGLT2i were not more effective for inpatient glycemic control than dipeptidyl peptidase 4 inhibitors and did not reduce insulin requirements when used in combination with insulin. Although SGLT2i can be considered for the treatment of congestive heart failure, they should be started close to or at the time of discharge. CONCLUSION: Although SGLT2i are a preferred pharmacotherapy class for the outpatient management of type 2 diabetes mellitus, there are considerable safety concerns when using them in a hospital setting, and avoidance is recommended.

Type 1 diabetes and low carbohydrate diets-Defining the degree of nutritional ketosis.

AIMS: Adopting a low- or very low-carbohydrate (LCD or VLCD) diet in type 1 diabetes mellitus (T1D) is a controversial intervention. The main fear is that these diets may increase the risk of diabetic ketoacidosis. However, there is little data about the ketoacidosis risk and the level of physiological nutritional ketosis in individuals following these diets. We aimed to define the level of ketosis in those with T1D following carbohydrate restricted diets in a real-world observational study. METHODS: Patients with T1D who had self-selected dietary carbohydrate restriction were enrolled from local clinics and were compared to those following an unrestricted regular carbohydrate control diet (RCCD). Participants completed a 3-day diary, documenting food intake, ketones, and blood/interstitial glucose concentrations. RESULTS: Participants were divided into three groups according to mean carbohydrate intake: VLCD (<50 g carbohydrates/day) n = 6, LCD (50-130 g carbohydrates/day) n = 6, and RCCD (>130 g carbohydrates/day) n = 3. Mean beta-hydroxybutyrate (BOHB) concentrations were 1.2 mmol/l (SD 0.14), 0.3 mmol/l (SD 0.12) and 0.1mmol/l (SD 0.05) in the VLCD, LCD and RCCD groups, respectively (p = 0.02). Post hoc Dunn test demonstrated this reached statistical significance between the VLCD and RCCD groups (p = 0.02). CONCLUSION: Carbohydrate restricted diets, in particular VLCDs, are associated with a higher BOHB level. However, the degree of ketosis seen is much lower than we expected, and significantly lower than the level typically associated with diabetic ketoacidosis. This may suggest the risk of ketoacidosis is lower than feared, although safety will need to be evaluated further in large scale randomised trials.

Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

Impact of school-supervised ultra-long-acting basal insulin injections on ketosis in youth with T1D and elevated haemoglobin A1c: A pilot study.

BACKGROUND: In youth with type 1 diabetes (T1D), high haemoglobin A1c (HbA1c) levels are associated with an increased risk for diabetic ketoacidosis (DKA). AIMS: This study examined whether daily school-supervised basal insulin injections were feasible and if they reduced the risk of morning ketosis in children and adolescents with high HbA1c levels. We hypothesized that supervised glargine and degludec would reduce the risk of ketosis and that the prolonged action of degludec would protect from ketosis after consecutive days of unsupervised injections. MATERIALS & METHODS: After a 2-4-week run-in, youth (10-18 years, HbA1c ≥ 8.5%) managing T1D with injections were randomized to school-supervised administration of degludec or glargine for 4 months. School nurses observed daily blood ß-hydroxybutyrate (BHB) and glucose checks. During COVID closures, the research team supervised procedures remotely. RESULTS: Data from 28 youth (age 14.3 ± 2.3 years, HbA1c 11.4 ± 1.9%, 64% F) were analysed. School-supervised injections of both basal insulins for 1-4 days progressively lowered the percent of participants with elevated BHB. The percent of participants with elevated BHB (≥0.6 mmol/L) after 2 days of unsupervised basal insulin doses at home was greater in the glargine than degludec group but had a high p-value (17.2% vs. 9.0%, p = 0.3). HbA1c was unchanged in both groups. DISCUSSION: In youth with T1D at high risk for DKA, daily supervised long-acting insulin administration decreased the probability of elevated ketone levels on subsequent school days, regardless of basal insulin type. A larger sample size may have demonstrated that the longer action profile of degludec would offer additional protection from ketosis during days of not attending school. CONCLUSION: Engaging school-based caregivers in management of youth with T1D on injected insulin may decrease clinically significant ketosis and minimize acute complications of diabetes.

Safety of sodium-glucose cotransporter 2 inhibitors in elderly patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are particularly effective in preventing adverse outcomes of heart failure and chronic kidney disease, which are highly prevalent in the elderly. Here, we aimed to access the safety of SGLT2i in elderly patients with type 2 diabetes. MATERIALS AND METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) reporting safety outcomes of the elderly (≥65 years) patients with type 2 diabetes, randomized to an SGLT2i or placebo. We recorded the incidence of acute kidney injury, volume depletion, genital tract infections, urinary tract infections, bone fractures, amputations, diabetic ketoacidosis, hypoglycaemia and drug discontinuation, by group of treatment. RESULTS: Of the 130 RCTs screened, only six reported data on elderly patients. In total, 19 986 patients were included. The SGLT2i discontinuation rate was approximately 20%. The risk of acute kidney injury was significantly lower among SGLT2i users compared with placebo [risk ratio (RR) 0.73; 95% CI 0.62-0.87]. SGLT2i were associated with a six-fold increased risk of genital tract infections (RR 6.55; 95% CI 2.09-20.5). The rate of amputations was increased only among canagliflozin users (RR 1.94, 95% CI 1.25-3). The risk of fractures, urinary tract infection, volume depletion, hypoglycaemia and diabetic ketoacidosis was similar between SGLT2i and placebo. CONCLUSIONS: SGLT2is were well tolerated in the elderly. However, older patients are underrepresented in most RCTs and a call for action is need to favour clinical trials reporting safety outcomes stratified by age.

SGLT2 Inhibition in Type 1 Diabetes with Diabetic Kidney Disease: Potential Cardiorenal Benefits Can Outweigh Preventable Risk of Diabetic Ketoacidosis.

PURPOSE OF REVIEW: The aim of this review is to summarize existing research investigating the use of sodium glucose cotransporter-2 (SGLT2) inhibitors in patients with type 1 diabetes mellitus (T1DM) while highlighting potential strategies to mitigate the risk of diabetic ketoacidosis (DKA). RECENT FINDINGS: SGLT2 inhibitors have been studied in patients with T1DM in phase 3 clinical trials such as the inTandem, DEPICT, and EASE trials, which demonstrated consistent reductions in HbA1c. Secondary analyses of these trials have also reported potential kidney protective effects that are independent of improved glycemic control. However, trials in patients with type 2 diabetes mellitus (T2DM) have found an increased risk of DKA with SGLT2 inhibitors, a serious concern in patients with T1DM. SGLT2 inhibitors provide cardiovascular benefits and kidney protection in patients with T2DM and are a promising therapeutic option for patients with T1DM due to overlapping pathophysiological mechanisms. However, SGLT2 inhibitors increase the risk of DKA, and there is currently a lack of research investigating the beneficial effects of SGLT2 inhibitors in patients with T1DM. Preventative measure for DKA would have to be implemented and the risks would need to be carefully balanced with the benefits offered by SGLT2 inhibitors. Additional research will also be required to determine the kidney protective effects of SGLT2 inhibitors in patients with T1DM and diabetic kidney disease and to quantify the risk of DKA after the implementation of preventative measures, proper patient education, and ketone monitoring.

Re-examining the widespread policy of stopping sodium-glucose cotransporter-2 inhibitors during acute illness: A perspective based on the updated evidence.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or chronic kidney disease, the risk of DKA is similar to placebo. Over the course of the COVID-19 pandemic, cases of DKA have also been reported in cases of COVID-19 hospitalizations. Consensus guidelines have recommended that SGLT2 inhibitors should be avoided in cases of serious illness and suggest they are not recommended for routine in-hospital use. However, recent data suggest potential beneficial effects of SGLT2 inhibitors in the setting of acute illness with COVID-19 with no increase in adverse events and low rates of DKA, which were non-severe. Given the low rates of DKA in cardiovascular outcome trials and in hospitalized patients with type 2 diabetes, the potential for SGLT2 inhibitors not being re-initiated following discharge and their cardiovascular and kidney benefits, we believe the practice of routine 'sick day' guidance should be re-examined based on current evidence with a call for further research in this area. Furthermore, high-quality trials of initiation of SGLT2 inhibitors in people admitted to hospital with cardiovascular disease or kidney disease, and trials of continuation of SGLT2 inhibitors in people, with careful monitoring of DKA should be conducted. These should be further supplemented with large observational studies.

Selecting an intervention to prevent ketoacidosis at diabetes diagnosis in children using a behavior change framework.

OBJECTIVE: The rate of diabetic ketoacidosis (DKA), a preventable, life-threatening complication of diabetes, at the time of diagnosis in children remains unacceptably high worldwide. We describe our initial approach to selecting a national DKA prevention strategy, to be implemented by the Canadian Pediatric Endocrine Group DKA Prevention Working Group, informed by a framework for behavior change interventions. METHODS: Existing interventions were identified from a systematic review and our own gray literature search. We then characterized interventions using the Behavior Change Wheel, a framework to inform and drive behavior change, and matched interventions to behavioral targets, audiences, and identified barriers and facilitators. Feedback from the CPEG DKA prevention working group was incorporated into the intervention plan. RESULTS: We identified 27 interventions. Our proposed target behaviors are: (1) prompt recognition of symptoms of diabetes in children; (2) urgent attendance to medical care with a request for an office-based test for diabetes; and (3) rapid confirmation of diagnosis and urgent consultation with pediatric diabetes experts. We initially identified four possible intervention functions including education, training, environment restructuring, and enablement. Feedback from the working group favored education intervention functions including symptom recognition messages targeting parents, caregivers, teachers, and providers and messages about how to make a rapid diagnosis and need for urgent referral targeting providers. CONCLUSIONS: The Behavior Change Wheel has been used successfully in selecting interventions in other clinical areas. We describe how we used this framework to provide a foundation for developing an intervention to prevent DKA at diabetes diagnosis in children.

Inpatient Perioperative Euglycemic Diabetic Ketoacidosis Due to Sodium-Glucose Cotransporter-2 Inhibitors - Lessons From a Case Series and Strategies to Decrease Incidence.

OBJECTIVE: To identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events. METHODS: Electronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmol/L, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA. RESULTS: A total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients; 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively. CONCLUSION: Euglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped.

Do the benefits of sodium-glucose cotransporter 2 inhibitors exceed the risks in patients with type 1 diabetes?

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are well-established means of improving glycemia and preventing cardio-renal events in patients with type 2 diabetes. However, their efficacy and safety have yet to be fully characterized in patients with type 1 diabetes (T1D). We studied patients with T1D who regularly attended one of five diabetes centers and treated with an SGLT2i (ipragliflozin or dapagliflozin) for >52 weeks, and the changes in HbA1c, body mass, insulin dose, and laboratory data were retrospectively evaluated and adverse events (AEs) recorded during December 2018 to April 2021. A total of 216 patients with T1D were enrolled during the period. Of these, 42 were excluded owing to short treatment periods and 15 discontinued their SGLT2i. The mean changes in glycated hemoglobin (HbA1c), body mass, and insulin dose were -0.4%, -2.1 kg, and -9.0%, respectively. The change in HbA1c was closely associated with the baseline HbA1c (p < 0.001), but not with the baseline body mass or renal function. The basal and bolus insulin doses decreased by 18.2% and 12.6%, respectively, in participants with a baseline HbA1c <8%. The most frequent AE was genital infection (2.8%), followed by diabetic ketoacidosis (DKA; 1.4%). None of the participants experienced severe hypoglycemic events. In conclusion, the administration of an SGLT2i in addition to intensive insulin treatment in patients with T1D improves glycemic control and body mass, without increasing the incidence of hypoglycemia or DKA.

Disparities in Utilization and Outcomes With Continuous Subcutaneous Insulin Infusion in Young Adults With Type 1 Diabetes.

OBJECTIVE: To evaluate which factors determine utilization patterns and outcomes of continuous subcutaneous insulin infusion (CSII) in young adults with type 1 diabetes. METHODS: Utilizing the Optum deidentified electronic health record data set between 2008 to 2018 to perform a retrospective cohort study, we identified 2104 subjects with type 1 diabetes aged 18 to 30 years. We evaluated the effect of race on determining CSII utilization, HbA1c (%), and hospital admission for diabetic ketoacidosis (DKA). Crude and adjusted estimates were computed using logistic regression and linear mixed models. RESULTS: There was low CSII utilization among individuals who were Black, Hispanic, male, and those with governmental insurance. These groups also demonstrated higher HbA1c levels. Subjects who were Black, Hispanic, and those with governmental insurance had higher odds of DKA. Even when commercially insured, Black and Hispanic subjects demonstrated higher HbA1c levels, and Black individuals had higher odds of DKA. CONCLUSION: In a large electronic health record database in the U.S., there was low CSII utilization overall, particularly in Black and Hispanic minorities, despite CSII showing superior HbA1c control without an increase in DKA events.

Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes. MATERIALS AND METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to 13 June 2019 for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with control in patients with type 2 diabetes. Paired reviewers independently screened citations, assessed the risk of bias and extracted data. Peto's method was used as the primary approach to pool the effect of SGLT2 inhibitors on DKA. Sensitivity analyses with the alternative effect measure (risk ratio) or pooling method (Mantel-Haenszel), the use of continuity correction of 0.5 for zero-event trials or a generalized linear mixed model were conducted. Six preplanned subgroup analyses were performed to explore heterogeneity. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence. RESULTS: A total of 39 RCTs were included, involving 60 580 patients and 85 DKA events. SGLT2 inhibitors were statistically associated with an increased risk of DKA versus control (SGLT2 inhibitors: 62/34 961 [0.18%] vs. control: 23/25 211 [0.09%], Peto odds ratio [OR] 2.13, 95% confidence interval [CI] 1.38 to 3.27, I2 = 8%; RD 1.7 more events, 95% CI 0.6 more to 3.4 more events per 1000 over 5 years; high-quality evidence). Sensitivity analyses showed similar results. The subgroup analyses by mean age (interaction P = 0 .02) and length of follow-up (interaction P = 0 .03) showed a larger relative effect among older patients (aged ≥60 years) and those with longer use of SGLT2 inhibitors (>52 weeks). CONCLUSIONS: High-quality evidence suggests that SGLT2 inhibitors may increase the risk of DKA in patients with type 2 diabetes. The apparent differences in treatment effects among patients of a different age or follow-up were probable, suggesting the advisability of caution in patients with long-term use of SGLT2 inhibitors or in older patients.

[The Management of Blood Glucose Should be Emphasized in the Treatment of COVID-19].

Based on the higher mortality and the higher proportion of critically ill adults in coronavirus disease 2019 (COVID-19) patients with diabetes, good inpatient glycemic control is particularly important in the comprehensive treatment of COVID-19. Individualized blood glucose target goals and treatment strategies should be made according to specific circumstances of COVID-19 inpatients with diabetes. For mild patients, a strict glycemic control target (fasting plasma glucose (FPG) 4.4-6.1 mmol/L, 2-hour postprandial plasma glucose (2 h PG) 6.1-7.8 mmol/L) are recommended; a target for the glycemic control of common type patients (FPG 6.1-7.8 mmol/L, 2 h PG 7.8-10.0 mmol/L) and subcutaneous insulin deliver therapy are recommended; a target nonfasting blood glucose range of 10.0 mmol or less per liter for severe-type COVID-19 patients, a relatively Less stringent blood glucose control target (FPG 7.8-10.0 mmol/L, 2 h PG 7.8-13.9 mmol/L) for critically ill patients and intravenous insulin infusion therapy are recommended. Due to the rapid changes in the condition of some patients, the risk of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar status (HHS) maybe occur during the treatment. Blood glucose monitoring, dynamic evaluation and timely adjustment of strategies should be strengthened to ensure patient safety and promote early recovery of patients.

[Insulin pump treatment: For whom and how to set it up on an outpatient?] / Traitement par pompe à insuline : pour qui et comment le mettre en place en ambulatoire ?

Pump therapy has existed for over 40 years and provides a more flexible delivery of insulin. To date, almost 25% of type 1 diabetic patients have chosen this therapeutic option. In recent years, it has also been offered to patients with type 2 insulin-requiring diabetes. The choice of insulin pump is based on its indication, the patient's preference, lifestyle and knowledge of the disease. A risk of developing ketoacidosis in case of interruption of insulin delivery exists. Its implementation therefore requires a specialized interdisciplinary care team available in case of emergency.

L'insulinothérapie par pompe existe depuis plus de 40 ans et permet une délivrance plus flexible de l'insuline. À ce jour, près de 25% des patients diabétiques de type 1 ont choisi cette option thérapeutique. Depuis quelques années, elle est aussi proposée aux patients diabétiques de type 2 insulino-requérants. Le choix de la pompe à insuline repose sur son indication, la préférence du patient, son style de vie et ses connaissances de la maladie. Un risque de survenue d'acidocétose en cas d'interruption de la délivrance d'insuline existe. Sa mise en place nécessite donc une équipe de soins interdisciplinaire spécialisée et disponible en cas d'urgence.

Marked improvement in HbA1c following commencement of flash glucose monitoring in people with type 1 diabetes.

AIMS/HYPOTHESIS: Minimal evidence supports the efficacy of flash monitoring in lowering HbA1c. We sought to assess the impact of introducing flash monitoring in our centre. METHODS: We undertook a prospective observational study to assess change in HbA1c in 900 individuals with type 1 diabetes following flash monitoring (comparator group of 518 with no flash monitoring). Secondary outcomes included changes in hypoglycaemia, quality of life, flash monitoring data and hospital admissions. RESULTS: Those with baseline HbA1c ≥58 mmol/mol (7.5%) achieved a median -7 mmol/mol (interquartile range [IQR] -13 to -1) (0.6% [-1.2 to -0.1]%) change in HbA1c (p < 0.001). The percentage achieving HbA1c <58 mmol/mol rose from 34.2% to 50.9% (p < 0.001). Median follow-up was 245 days (IQR 182 to 330). Individuals not using flash monitoring experienced no change in HbA1c across a similar timescale (p = 0.508). Higher HbA1c (p < 0.001), younger age at diagnosis (p = 0.003) and lower social deprivation (p = 0.024) were independently associated with an HbA1c fall of ≥5 mmol/mol (0.5%). More symptomatic (OR 1.9, p < 0.001) and asymptomatic (OR 1.4, p < 0.001) hypoglycaemia was reported after flash monitoring. Following flash monitoring, regimen-related and emotional components of the diabetes distress scale improved although the proportion with elevated anxiety (OR 1.2, p = 0.028) and depression (OR 2.0, p < 0.001) scores increased. Blood glucose test strip use fell from 3.8 to 0.6 per day (p < 0.001). Diabetic ketoacidosis admissions fell significantly following flash monitoring (p = 0.043). CONCLUSIONS/INTERPRETATION: Flash monitoring is associated with significant improvements in HbA1c and fewer diabetic ketoacidosis admissions. Higher rates of hypoglycaemia may relate to greater recognition of hitherto unrecognised events. Impact upon quality of life parameters was mixed but overall treatment satisfaction was overwhelmingly positive.