Risk Of Ketoacidosis Research Articles

Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the U.S., evaluating SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE patients and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PS) based on clinical and demographic factors. Hazard ratios (HR with 95% confidence intervals) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 0.50-0.76), end-stage renal disease (HR 0.40, 0.20-0.80), heart failure (HR 0.72, 0.56-0.92), and emergency department visits (HR 0.90, 0.82-0.99). Risks of all-cause mortality (HR 0.89, 0.65-1.21), lupus nephritis (HR 0.67, 0.38-1.15), myocardial infarction (HR 0.81, 0.54-1.23), stroke (HR 1.03, 0.74-1.44), and hospitalizations (HR 0.76, 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.065, 0.53-2.14) and fractures (HR 0.95, 0.66-1.36). In this emulated clinical trial, SGLT2i vs. DPP4i use was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Knowledge and awareness of ketoacidosis associated with high exposure to acetone-containing products: A crosssectional assessment

Purpose: To assess the knowledge and awareness of the Jordanian public about the hazards associated with high levels of exposure to acetone-containing products. Methods: The study was conducted between September 2019 and December 2020. An electronic anonymous questionnaire was distributed via different channels to be self-completed by the study population. Socio-demographic characteristics, knowledge about acetone-containing nail polish removers and sterilizing products, and awareness about the risk of ketoacidosis associated with high degree of exposure to these products, were assessed. Results: The findings revealed that a majority of participants were aware of the presence of acetone in nail polish removers (92.61 %) and sterilizing products (84.41 %), regardless of gender, age, educational type and educational level. In addition, females (70.4 or 83.0 %), youngest age group (70.7 or 83.0 %), those with health-related education (56.6 or 76.0 %), and graduates (72.0 or 83.9 %) were significantly (p < 0.05) more aware about the safety of these products if inhaled or exposed to flame sources, respectively, than their peers. Moreover, concerning the risks of developing ketoacidosis and raised liver ketone levels as hazards associated with the high degree of exposure to acetone-containing products, females (44.2, 41.9 and 50.6 %), those with health-related education (64.1, 63.4 and 73.3 %), youngest age group (47.4, 44.6 and 56.5 %), and graduates (45.3, 43.5 and 52.8 %), respectively, were significantly more aware than the others (p < 0.05). Conclusion: These findings indicate signs of significantly poor awareness about the serious risks associated with acetone-caused ketoacidosis among the study population. Therefore, well-organized educational campaigns are needed to enlighten graduates with health-related education and to improve public perception of the health hazards associated with human exposure to acetone-containing products.

Starvation Ketoacidosis on the Acute Medical Take: An Easily Missed Complication of the Keto Diet.

Always check ketones in patients with an unexplained metabolic acidosis; there can be overlap between starvation, alcohol-related and lactic acidosis.Management of starvation ketoacidosis is often empirical, involving close monitoring of fluid status and electrolytes.Clinicians should discuss the risk of ketoacidosis associated with the ketogenic diet in women who plan to breast-feed and lose weight following pregnancy.

Association of circulating inflammatory proteins with type 2 diabetes mellitus and its complications: a bidirectional Mendelian randomization study.

Increasing evidence indicates that immune response underlies the pathology of type 2 diabetes (T2D). Nevertheless, the specific inflammatory regulators involved in this pathogenesis remain unclear. We systematically explored circulating inflammatory proteins that are causally associated with T2D via a bidirectional Mendelian randomization (MR) study and further investigated them in prevalent complications of T2D. Genetic instruments for 91 circulating inflammatory proteins were derived from a genome-wide association study (GWAS) that enrolled 14,824 predominantly European participants. Regarding the summary-level GWASs of type 2 diabetes, we adopted the largest meta-analysis of European population (74,124 cases vs. 824,006 controls) and a prospective nested case-cohort study in Europe (9,978 cases vs. 12,348 controls). Summary statistics for five complications of T2D were acquired from the FinnGen R9 repository. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted median and maximum likelihood methods were employed as supplementary analyses. Results from the two T2D studies were combined in a meta-analysis. Sensitivity analyses and phenotype-wide association studies (PheWAS) were performed to detect heterogeneity and potential horizontal pleiotropy in the study. Genetic evidence indicated that elevated levels of TGF-α (OR = 1.16, 95% CI = 1.15-1.17) and CX3CL1 (OR = 1.30, 95% CI = 1.04-1.63) promoted the occurrence of T2D, and increased concentrations of FGF-21 (OR = 0.87, 95% CI = 0.81-0.93) and hGDNF (OR = 0.96, 95% CI = 0.95-0.98) mitigated the risk of developing T2D, while type 2 diabetes did not exert a significant influence on said proteins. Elevated levels of TGF-α were associated with an increased risk of ketoacidosis, neurological complications, and ocular complications in patients with T2D, and increased concentrations of FGF-21 were potentially correlated with a diminished risk of T2D with neurological complications. Higher levels of hGDNF were associated with an increased risk of T2D with peripheral vascular complications, while CX3CL1 did not demonstrate a significant association with T2D complications. Sensitivity analyses and PheWAS further ensure the robustness of our findings. This study determined four circulating inflammatory proteins that affected the occurrence of T2D, providing opportunities for the early prevention and innovative therapy of type 2 diabetes and its complications.

The emerging risks of ketoacidosis and its detection by an innovative Breath Ketone Analyser - KetoMetrics

Ketoacidosis is a dangerous condition, of which diabetic ketoacidosis and euglycemic diabetic ketoacidosis are increasingly common in the community due to uncontrol diabetes and its medical management. This paper describes the common situations leading to ketoacidosis and the dilemma facing clinicians in handling this life-threatening condition. The development of an innovative Breath Ketone Analyser has improved the point of care in diabetes management by detecting and preventing the development of dangerous ketoacidosis.

Ketone production and excretion even during mild hyperglycemia and the impact of sodium-glucose co-transporter inhibition in type 1 diabetes

AimsWe aimed to determine if ketone production and excretion are increased even at mild fasting hyperglycemia in type 1 diabetes (T1D) and if these are modified by ketoacidosis risk factors, including sodium-glucose co-transporter inhibition (SGLTi) and female sex. MethodsIn secondary analysis of an 8-week single-arm open-label trial of empagliflozin (NCT01392560) we evaluated ketone concentrations during extended fasting and clamped euglycemia (4–6 mmol/L) and mild hyperglycemia (9–11 mmol/L) prior to and after treatment. Plasma and urine beta-hydroxybutyrate (BHB) concentrations and fractional excretion were analyzed by metabolomic analysis. ResultsForty participants (50 % female), aged 24 ± 5 years, HbA1c 8.0 ± 0.9 % (64 ± 0.08 mmol/mol) with T1D duration of 17.5 ± 7 years, were studied. Increased BHB production even during mild hyperglycemia (median urine 6.3[3.5–13.6] vs. 3.5[2.2–7.0] µmol/mmol creatinine during euglycemia, p < 0.001) was compensated by increased fractional excretion (0.9 % [0.3–1.6] vs. 0.4 % [0.2–0.9], p < 0.001). SGLTi increased production and attenuated the increased BHB fractional excretion (decreased to 0.3 % during mild hyperglycemia, p < 0.001), resulting in higher plasma concentrations (increased to 0.21 [0.05–0.40] mmol/L, p < 0.001), particularly in females (interaction p < 0.001). ConclusionsEven mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion, in T1D. However, SGLTi exaggerates production and partially reduces compensatory excretion, particularly in women.

Continuous glucose monitoring versus blood glucose monitoring for risk of severe hypoglycaemia and diabetic ketoacidosis in children, adolescents, and young adults with type 1 diabetes: a population-based study

The effect of continuous glucose monitoring on the risk of severe hypoglycaemia and ketoacidosis in patients with diabetes is unclear. We investigated whether rates of acute diabetes complications are lower with continuous glucose monitoring, compared with blood glucose monitoring, and which metrics predict its risk in young patients with type 1 diabetes. In this population-based cohort study, patients were identified from 511 diabetes centres across Austria, Germany, Luxembourg, and Switzerland participating in the Diabetes Prospective Follow-up initiative. We included people with type 1 diabetes aged 1·5-25·0 years, with a diabetes duration of more than 1 year, who had been treated between Jan 1, 2014, and June 30, 2021, and had an observation time of longer than 120 days in the most recent treatment year. Severe hypoglycaemia and ketoacidosis rates during the most recent treatment year were examined in people using continuous glucose monitoring and in those using blood glucose monitoring. Adjustments of statistical models included age, sex, diabetes duration, migration background, insulin therapy (pump or injections), and treatment period. Rates of severe hypoglycaemia and diabetic ketoacidosis were evaluated by several continuous glucose monitoring metrics, including percentage of time below target glucose range (<3·9 mmol/L), glycaemic variability (measured as the coefficient of variation), and mean sensor glucose. Of 32 117 people with type 1 diabetes (median age 16·8 years [IQR 13·3-18·1], 17 056 [53·1%] males), 10 883 used continuous glucose monitoring (median 289 days per year), and 21 234 used blood glucose monitoring. People using continuous glucose monitoring had lower rates of severe hypoglycaemia than those using blood glucose monitoring (6·74 [95% CI 5·90-7·69] per 100 patient-years vs 8·84 [8·09-9·66] per 100 patient-years; incidence rate ratio 0·76 [95% CI 0·64-0·91]; p=0·0017) and diabetic ketoacidosis (3·72 [3·32-4·18] per 100 patient-years vs 7·29 [6·83-7·78] per 100 patient-years; 0·51 [0·44-0·59]; p<0·0001). Severe hypoglycaemia rates increased with percentage of time below target glucose range (incidence rate ratio 1·69 [95% CI 1·18-2·43]; p=0·0024, for 4·0-7·9% vs <4·0% and 2·38 [1·51-3·76]; p<0·0001, for ≥8·0% vs <4·0%) and glycaemic variability (coefficient of variation ≥36% vs <36%; incidence rate ratio 1·52 [95% CI 1·06-2·17]; p=0·022). Diabetic ketoacidosis rates increased with mean sensor glucose (incidence rate ratio 1·77 [95% CI 0·89-3·51], p=0·13, for 8·3-9·9 mmol/L vs <8·3 mmol/L; 3·56 [1·83-6·93], p<0·0001, for 10·0-11·6 mmol/L vs <8·3 mmol/L; and 8·66 [4·48-16·75], p<0·0001, for ≥11·7 mmol/L vs <8·3 mmol/L). These findings provide evidence that continuous glucose monitoring can reduce severe hypoglycaemia and ketoacidosis risk in young people with type 1 diabetes on insulin therapy. Continuous glucose monitoring metrics might help to identify those at risk for acute diabetes complications. German Center for Diabetes Research, German Federal Ministry of Education and Research, German Diabetes Association, and Robert Koch Institute.

Blood glucose control with different treatment regimens in type 2 diabetes patients hospitalized with COVID-19 infection: A retrospective study.

Coronavirus disease (COVID-19) is closely associated with hyperglycemia and a worse prognosis in patients with a previous diagnosis of type 2 diabetes mellitus. A few studies investigated the effects of diabetes treatment regimens in these patients during hospitalization. Here, we evaluate the impact of insulin and non-insulin therapy on glucose control in patients with type 2 diabetes admitted with COVID-19. This is a retrospective study including 359 COVID-19 patients with type 2 diabetes. Patients were divided into 2 groups according to diabetes treatment during hospitalization. The first group included patients treated with insulin only, and the second group patients treated with other antidiabetic agents with or without insulin. Average blood glucose was higher in the insulin-only treatment group (201 ± 66 mg/dL vs 180 ± 71 mg/dL, P = .004), even after excluding mechanically ventilated patients (192 ± 69 vs 169 ± 59 mg/dL, P = .003). In patients with moderate severity of COVID-19, average blood glucose was also significantly higher in the insulin-only treated group (197 ± 76 vs 168 ± 51 mg/dL, P = .001). Most patients (80%) in the combination treatment group received metformin. Moderately affected COVID-19 patients with type 2 diabetes could safely be treated with antihyperglycemic medications with or without insulin.

Monitoring of continuous subcutaneous insulin infusion treatment in Portugal and its implications for diabetes management.

Intensive insulin therapy in the treatment of type 1 diabetes can, in place of multiple daily injections of subcutaneous insulin (MDI), be performed with continuous subcutaneous insulin infusion (CSII) systems. This method allows for better glycemic control and thus reduces the risk of complications of the disease. The aim of this study was to evaluate the results of treatment with CSII in Portugal. A retrospective analysis of the records on the national CSII platform was carried out between January 2010 and August 2021. All the registered patients are followed in certified CSII treatment centers in Portugal. Of the 7135 registered patients, 3807 were excluded due to absence of monitoring data. The reasons for treatment were analyzed and a comparison was made between patients with and without CSII. The statistical significance considered was α < 0.05. A total of 3328 patients were included in the study, 1136 under MDI and 2192 under CSII. The main reasons for CSII use were marked glycemic variability (25%) and HbA1c greater than 7% (23%). Patients under CSII had a lower HbA1c (7.7 ± 1.0% vs. 8.0 ± 1.5%, p < 0.001), as well as a lower frequency of episodes of severe hypoglycemia (1.4 vs. 3.3 per 100 patient-years, p < 0.001), and ketoacidosis (1 vs. 2.4 per 100 patient-years, p < 0.001). The present analysis validates the advantage of using CSII in metabolic control and reduction of acute complications of type 1 diabetes, both severe hypoglycemia and ketoacidosis, in the Portuguese population. CSII therapy is classically associated with an increased risk of ketoacidosis; however, in experienced centers and adequate patient education, the opposite is found.

ODP183 Diabetic Ketoacidosis Precipitated by Ketogenic Diet and SGLT-2 Inhibitor Use in an Individual with T2DM

Abstract Background SGLT-2 inhibitors have been associated with increased risk of ketoacidosis even with normal blood glucose levels. A ketogenic diet is a low-carb, high-fat diet which has recently gained popularity for weight loss by producing a state of ketosis. We present this case to emphasize the risk of ketoacidosis in patients on SGLT-2 inhibitors and a ketogenic diet. Clinical Case A 48-year-old woman with a 16-year history of T2DM presented to the ER with a 3-day history of upper abdominal cramping and headaches, decreased urine output, and progressively worsening nausea and vomiting. Her glycated hemoglobin level was 9.4% (n: 4-6%) and her blood glucose readings were not elevated during this time. Other medical issues include dyslipidemia, transaminitis and hypertension. She does not smoke or drink alcohol. She takes glimepiride 0.5 mg daily and canagliflozin was added approximately 1.5 weeks prior to presentation. She was on a ketogenic diet. A few days prior to these symptoms she was in the process of moving out of her home, spending long days physically exerting herself. On exam she was in mild distress with dry mucous membranes. Vitals showed tachycardia (119BPM) but otherwise were stable. Labs revealed that she was severely acidotic with an anion gap of &amp;gt;27 and pH &amp;lt; 6.9 (n: 7.34-7.43), with urinalysis positive for ketones (2+, n: negative), protein (3+, n: negative), and glucose (3+, n: negative). Complete blood count showed leukocytosis (WBC: 18,000, n: 4. 00-12. 00*10 3 /mcL). Complete metabolic panel showed hyponatremia (130, n: 136-145mmol/L), elevated glucose (305, n: 70-99,g/dL), and low bicarbonate (&amp;lt;5, n: 22-30mmol/L). A chest X-ray, lumbar puncture and CT of head and abdomen were unrevealing. She was admitted to the ICU for treatment of suspected DKA with severe acidosis and hypovolemia. She was hydrated with IV fluids and was started on an insulin drip according to DKA protocol. Her anion gap closed in 22 hours. The patient spent 3 days in the ICU and 1 day on general floor before discharge on home medications and was advised to follow up with endocrinology. At follow up 2 months later her C-peptide was 2.14 (0.78-5.19 ng/mL) and GAD65 antibody assay was 0. 00 (&amp;lt;0. 02 nmol/L), the SGLT-2 inhibitor was discontinued, and she was instead started on a GLP-1 agonist. Conclusion The mechanism behind DKA with SGLT-2 inhibitor use involves glycosuria and volume depletion, lowering the insulin-to-glucagon ratio, while stimulating lipolysis. The addition of a low carbohydrate or ketogenic diet produces a state of ketosis as fat is utilized for energy and ketones are produced, further promoting DKA. With increased use of SGLT-2 inhibitors in patients with and without diabetes mellitus extreme caution should be exercised in prescribing SGLT-2 inhibiters in a patient on a low carbohydrate diet. Presentation: No date and time listed

Decreased occurrence of ketoacidosis and preservation of beta cell function in relatives screened and monitored for type 1 diabetes in Australia and New Zealand.

Islet autoantibody screening of infants and young children in the Northern Hemisphere, together with semi-annual metabolic monitoring, is associated with a lower risk of ketoacidosis (DKA) and improved glucose control after diagnosis of clinical (stage 3) type 1 diabetes (T1D). We aimed to determine if similar benefits applied to older Australians and New Zealanders monitored less rigorously. DKA occurrence and metabolic control were compared between T1D relatives screened and monitored for T1D and unscreened individuals diagnosed in the general population, ascertained from the Australasian Diabetes Data Network. Between 2005 and 2019, 17,105 relatives (mean (SD) age 15.7 (10.8) years; 52% female) were screened for autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2. Of these, 652 screened positive to a single and 306 to multiple autoantibody specificities, of whom 201 and 215, respectively, underwent metabolic monitoring. Of 178 relatives diagnosed with stage 3 T1D, 9 (5%) had DKA, 7 of whom had not undertaken metabolic monitoring. The frequency of DKA in the general population was 31%. After correction for age, sex and T1D family history, the frequency of DKA in screened relatives was >80% lower than in the general population. HbA1c and insulin requirements following diagnosis were also lower in screened relatives, consistent with greater beta cell reserve. T1D autoantibody screening and metabolic monitoring of older children and young adults in Australia and New Zealand, by enabling pre-clinical diagnosis when beta cell reserve is greater, confers protection from DKA. These clinical benefits support ongoing efforts to increase screening activity in the region and should facilitate the application of emerging immunotherapies.

Potential Clinical Applications for Continuous Ketone Monitoring in the Hospitalized Patient with Diabetes.

Purpose of ReviewIn this review, the authors discuss potential clinical applications for continuous ketone monitoring (CKM) in a broad continuum of clinical settings from pre-hospital care and the emergency department to acute inpatient management and post-discharge follow-up.Recent FindingsThough in its early stages, the concept of a novel continuous ketone sensing technology exerts great potential for use in the detection and hospital management of DKA, namely to overcome diagnostic barriers associated with ketoacidosis in patients with diabetes and obtain real-time BOHB levels, which may be useful in understanding both patients’ response to treatment and DKA trajectory. Peri- and intra-operative use of CKM technology can potentially be applied in a number of urgent and elective surgical procedures frequently underwent by patients with diabetes and in the observation of patients during peri-operative fasting. In transitional care management, CKM technology could potentially facilitate patients’ safe transition through levels of care, following hospital discharge from a DKA episode.SummaryThis evaluation of the literature presents the potential advantages of adopting CKM and integrating this technology into the care algorithm of patients at risk for ketoacidosis.

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes.

To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D). Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n=12) or placebo (n=11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater. During the 7- to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( -27.6 vs. -4.4mg/dL [-1.5 vs. -0.2 mmol/L]; P=0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants. When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

173-OR: Associations between Post-Discharge Care (PDC) and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults with Diabetes

Cognitive Impairment (CI) is associated with an increased risk of ketoacidosis (DKA) and severe hypoglycemia (SH) in persons with diabetes (DM) . Post-discharge Care (PDC) in nursing homes and home care facilities provides continuous medical care after hospital discharges. This study examined whether PDC is associated with lower CI-related hospital readmission for DKA and SH in US adults with DM (age &amp;gt;18) . Our study population includes 43,467 and 166,221 adults admitted for DKA and SH from the 2016-2018 National Readmission Database, among which 1492 (3.43%) and 822 (0.49%) had CI, respectively. Readmission was defined as hospitalization for all causes within 30 days after discharge. CI-related readmission risk was estimated by comparing those with and without CI using a multiple logistic regression model, adjusting for age, sex, primary payer, income level, disease severity, mortality risk at the index discharge, and PDC status. PDC as an effect modulator was tested as an interaction term of PDC and CI. For patients initially admitted for DKA, CI was associated with 62% (adjusted odds ratio (aOR) =1.62, 1.25-2.11) higher odds of readmission among those who were discharged to home. The CI-related increase in readmission risk disappeared if patients received PDC (aOR=1.05, 0.88-1.26) . For patients initially admitted for SH, CI was associated with 34% (aOR=1.34, 95% CI 1.08-1.66) higher odds of readmission among those discharged to home and a 32% lower odds of readmission if patients received PDC (aOR=0.68, 0.59-0.81) . CI was associated with increased readmission risks for SH and DKA among adults with DM discharged to home. This CI-related readmission risk was substantially lower in patients who received PDC, indicating the importance of PDC for people with DM and CI. Disclosure Y.Wang: None. P.Zhang: None. R.R.Fang: None. J.D.Brown: None. T.Jiao: None. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.

IDF21-0150 A dose-based comparison of safety among sodium-glucose co-transporter inhibitor-treated type1 diabetes patients

Background: The dose-wise variation in sodium-glucose co-transporter inhibitor (SGLTi) treated type 1 diabetes mellitus (T1DM) patients' safety profile remains poorly understood. Aim: Therefore, this study aims to study it. Method: A database search occurred in PubMed, Embase, and Scopus databases for double-blinded randomized controlled trials reporting the above outcomes. The risk of bias assessment of the reviewed RCTs happened using the Cochrane tool. Pairwise random-effect meta-analysis (DerSimonian and Laird method) was used to compare SGLTis’ safety between its mega (maximum dose in which it got tested in the reviewed trials) and low dosages and between SGLTi dosage irrespectively and placebo. The relative safety between respective and different generic SGLTi dosages was contrasted by network meta-analysis (NMA). The NMA models included double-blinded RCTs' data and excluded pooled safety data from RCTs with different follow-up duration to reduce the intransitivity risk. Effect-sizes got estimated in risk ratio (RR). The statistical significance estimation occurred at p<0.05 and 95% confidence interval (CI). Stata software, v16, was used for analysis. Results: This review incorporated fifteen studies sourcing data from 7,330 participants from 120 countries. The risk of bias among these studies was primarily low. Dose irrespectively SGLTis increased the risk of any adverse event-led study discontinuation (RR: 1.42; 95% CI: 1.04-1.93; I2: 14.8%), genital infection (RR: 3.18; 95% CI: 2.48-4.09; I2: 0%), and diabetic ketoacidosis (RR: 2.40; 95% CI: 1.23-4.64; I2: 27.4%). The mega and low doses were indifferent safety-wise. On NMA, compared to the respective different generic SGLT type 2 inhibitors (SGLT2i), the risk of any side effect, any adverse event-led study discontinuation, documented hypoglycemia, severe hypoglycemia, and urinary tract infection were lower with 2.5 mg empagliflozin, 50 mg ipragliflozin, 2.5 mg dapagliflozin, 10 mg dapagliflozin, and 50 mg ipragliflozin, respectively. The surface under the cumulative ranking curves for outcomes with statistically significant differences between two SGLT2i dosages supported these findings chiefly. Supplementary NMA that included trials of identical follow-up duration or mechanism of action closely replicated the preliminary NMA findings. Discussion: Using the GRADE Working Group’s (2004) approach, the statistically significant findings from all direct pairwise and indirect NMA comparisons were downgraded to moderate and low-quality evidence, respectively. The key strengths of this review include its comprehensive database search strategy, incorporation of double-blinded RCTs only (highest level of epidemiological evidence), and the intransitivity risk reduction strategies. Its main limitations include the poor representation of certain SGLTis tested by fewer trials (e.g., canagliflozin), a few unclear risks of bias components in the reviewed trials, and dependence of relative safety between two generic SGLT2i-dosages on indirect NMA comparisons. Regarding its implication, besides providing SGLTi-associated safety information, it will plausibly aid physicians in choosing T1DM patient-specific generic SGLTi type and dosage. Also, it emphasizes the need for different generic SGLTi-based multi-arm RCTs. To conclude, SGLTi treatment increases any adverse event-led study discontinuation, genital infection, and ketoacidosis risk in T1DM patients; however, the safety profile doesn't vary between its mega and low dosages. A relatively safer SGLTi dosage is available to ensure individualized diabetes care for specific SGLTi-dosage-related side effects in T1DM patients.

Dapagliflozin associated with higher risk of ketoacidosis in T2DM patients

Dapagliflozin associated with higher risk of ketoacidosis in T2DM patients

Increased Frequency of Diabetic Ketoacidosis: The Link With COVID-19 Pandemic.

Diabetic ketoacidosis is the most severe metabolic derangement due to prolonged insulin deficiency as in type 1 diabetes. Diabetic ketoacidosis, a life-threatening condition, is often diagnosed late. A timely diagnosis is mandatory to prevent its consequences, mainly neurological. The COVID-19 pandemic and lockdown have reduced the availability of medical care and access to hospitals. The aim of our retrospective study was to compare the frequency of ketoacidosis at the diagnosis of type 1 diabetes between the lockdown-post lockdown period and the previous two calendar years, in order to evaluate the impact of the COVID-19 pandemic. We retrospectively assessed the clinical and metabolic data atthe diagnosis of type 1 diabetes in children in the Liguria Region during 3 different timeperiods: calendar year 2018 (Period A), calendar year 2019 until February 23,2020 (Period B) and from February 24, 2020 onwards to March 31, 2021 (Period C). We analyzed 99 patients with newly-diagnosed T1DM from 01/01/2018 to 31/03/2021. Briefly, a younger age at diagnosis of T1DM was observed in Period 2 compared to Period 1 (p = 0.03). The frequency of DKA at clinical onset of T1DM was similar in Period A (32.3%) and Period B (37.5%), while it significantly increased in Period C (61.1%) compared to Period B (37.5%) (p = 0.03). PH values were similar in Period A (7.29 ± 0.14) and Period B (7.27 ± 0.17), while they were significantly lower in Period C (7.21 ± 0.17) compared to Period B (p = 0.04). An increase in the frequency of diabetic ketoacidosis has been documented in newly diagnosed pediatric patients in the Liguria Region during and after the lockdown period compared to previous calendar years. This increase could have been caused by the delay in diagnosis following the restrictions imposed by the lockdown with consequently reduced access to health care facilities. More information on the risks of ketoacidosis is desirable by means of social and medical awareness campaigns.

Steroid-induced diabetic ketoacidosis - case report

Background: Diabetic ketoacidosis (DKA) is an acute complication of diabetes, a severe metabolic disorder that requires urgent treatment. The aim of this article is to present a case of steroid-induced diabetes with complications. Case presentation: A young 25-year-old man without any co-morbid, presented to the emergency department with fever, vomiting, coughing, and buttock pain which started 3 days before. On the right gluteus, there was a hematoma approx. 10 × 5 cm with fluctuation. The patient had hyperglycemia (9.1 mmol/l), associated with high anion-gap metabolic acidosis, acute kidney injury (AKI), grossly elevated muscle enzymes, hyperkalemia, hyperphosphatemia, hypoalbuminemia, hypocalcemia and hypomagnesemia, and deranged liver function tests. The urine dipstick was grossly cola-colored and biochemically was positive for glucose, ketones, and proteins. Abscess drainage was performed, and Streptococcus pyogenes was isolated on culture and sensitivity. The patient was treated for DKA, complicated by an AKI and infection. Diabetes is confirmed based on glycosylated hemoglobin. Conclusion: The risk of ketoacidosis and hyperglycemia should be considered in the course of steroid therapy, even without a diagnosis of diabetes, in patients who abuse steroids or have risk factors for diabetes and obesity.

Outcome of COVID-19: Diabetes and Obesity

Today the world is facing one of the biggest crisis, due to a new beta-corona virus emerged from Wuhan in China, on December 2019. WHO declared ‘acute respiratory syndrome COVID-19 (SARS Co-2)’as a pandemic on March 12, 2020. Corona viruses are enveloped positive single stranded RNA viruses, causing severe acute respiratory syndrome in the infected individuals. The risk of getting infected by covid-19 is similar in all the individuals across the nation. But the outcome of the infection varies from one individual to another, depending on the comorbidities present in them. The most vulnerable group of patients in respect to severity of outcome of the infection are the once with unbalanced heath conditions like age (&gt;65 years), immune-compromised, hypertension, type 2 diabetes, increased insulin resistance, cardiovascular diseases, chronic kidney disease, chronic liver disease, vasculitis(vascular inflammation)and obesity. It is now a public knowledge that diabetes and obesity are a risk factor for any individual as these conditions can exacerbate the manifestations of COVID-19 infections thus increasing the severity of the condition, that may require hospitalization of the patient, later may even require intensive care unit or/and mechanical ventilation, with increased risk of mortality rates. In diabetic patients it is mainly due to failure in controlling the glucose levels and the risk of ketoacidosis. In patients with obesity lipid peroxidase creates reactive lipid aldehydes leading to poor prognosis.

Clinical study of autoantibodies in type 1 diabetes mellitus children with ketoacidosis or microalbuminuria.

AimsThe study aimed to investigate the value of autoantibodies in predicting the risk of ketoacidosis or microalbuminuria in children with type 1 diabetes mellitus.MethodsClinical data and laboratory indicators of 80 patients with type 1 diabetes admitted to the Department of Endocrinology in Tianjin Children's Hospital, from June 2017 to March 2019, were retrospectively analyzed. The patients were divided into two groups: diabetes without ketoacidosis group (n = 20) and diabetes with ketoacidosis group (n = 60). The differences in general data, laboratory test indexes, and autoantibodies between the two groups were analyzed. Finally, ROC curves and multivariate logistic regression analysis were used to explore the value of autoantibodies in patients with ketoacidosis or microalbuminuria.ResultsA total of 80 children with type 1 diabetes were assessed, including 35 boys and 45 girls, ranging in age from 10 months to 15 years. The concentration of GADA, IA2A, and ZnT8A was not statistically different between the two groups, but the positive rate of ZnT8A was statistically significant (p = 0.038) and had a diagnostic value for the occurrence of ketoacidosis (p = 0.025). ZnT8A‐positive patients had a higher titer of IA2A and a more frequent prevalence of GADA and IA2A than ZnT8A‐negative patients (p < 0.01). In multivariate logistic regression analyses, the presence of positive ZnT8A was associated with a higher risk of microalbuminuria independent of age, sex, and BMI (OR = 4.184 [95% CI 1.034~16.934], p = 0.045).ConclusionsThe positive ZnT8A had diagnostic value for ketoacidosis in children with type 1 diabetes and had the highest specificity among the three kinds of autoantibodies. Moreover, ZnT8A positivity was related to a higher titer of IA2A and more frequent occurrence of multiple diabetes‐related autoantibodies. Besides, the presence of positive ZnT8A was an independent risk factor of microalbuminuria in children with type 1 diabetes. Therefore, we can infer that positive ZnT8A may be related to ketoacidosis and microalbuminuria, accelerating the progression of T1DM.