Search Results (259)

Background and Clinical Significance: Diabetic ketoacidosis (DKA) is a common presentation of new-onset type 1 diabetes mellitus in children; however, severe DKA complicated by acute pancreatitis, dialysis-requiring acute kidney injury (AKI), severe hypertension, and neurological involvement is uncommon. Early recognition of these complications is essential because they may substantially increase morbidity and complicate standard DKA management; Case Presentation: An 11-year-old Saudi girl with morbid obesity (BMI 43 kg/m²), previously in good health, was brought to the emergency department after being found semi-conscious. She had experienced intermittent abdominal pain for five weeks and vomiting for four days. On presentation, she was critically ill, dehydrated, and confused (Glasgow Coma Scale 11/15) and exhibited Kussmaul breathing and abdominal tenderness. Laboratory investigations confirmed severe new-onset DKA, with a blood glucose level of 684 mg/dL, pH < 7.0, HbA1c 12.2% and an anion gap > 37 mEq/L. Despite standard DKA management, metabolic acidosis persisted and renal function progressively deteriorated, accompanied by oliguria and severe hypertension reaching 200 mmHg. By day 4, the patient developed anuria and marked creatinine elevation to 560 µmol/L. Brain magnetic resonance imaging demonstrated cerebral microhemorrhages in the setting of multifactorial encephalopathy. Continuous kidney replacement therapy was initiated for KDIGO stage 3 AKI with refractory metabolic acidosis. Autoimmune testing supported the diagnosis of type 1 diabetes mellitus, while renal biopsy demonstrated acute tubular injury; Conclusions: This case highlights a rare, severe multisystem presentation of pediatric DKA. Close monitoring for renal, neurological, pancreatic, and hypertensive complications is crucial, particularly when the clinical course does not improve as expected with standard therapy. Full article

Background: Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are widely prescribed for type 2 diabetes mellitus (T2DM) because of their cardiovascular and renoprotective benefits. However, their use is associated with euglycemic diabetic ketoacidosis (EDKA), a rare but potentially life-threatening complication characterized by severe ketoacidosis despite relatively normal blood glucose levels. Failure to discontinue SGLT-2 inhibitors before surgery, as recommended in current guidelines, together with perioperative fasting and surgical stress, increases the risk of EDKA. Diagnostic complexity is compounded when concurrent postoperative surgical complications provide an alternative explanation for persistent metabolic acidosis. Methods: A 71-year-old man with T2DM receiving uninterrupted empagliflozin underwent direct lateral interbody fusion under general anesthesia. On postoperative day 2, he developed severe high anion-gap metabolic acidosis (pH 7.204, HCO₃⁻ 10.1 mEq/L) with near-normal blood glucose levels (178 mg/dL). Pneumoperitoneum identified on imaging was attributed to Hemovac drain-related peritoneal injury, and emergent laparoscopic exploration was performed under a working diagnosis of surgical sepsis. Although surgical source control was successfully achieved, severe metabolic acidosis persisted postoperatively (pH 7.275). Euglycemic diabetic ketoacidosis is an uncommon diabetic complication associated with several perioperative risk factors, including prolonged fasting and surgical stress. Subsequent serum ketone analysis demonstrated markedly elevated beta-hydroxybutyrate levels (4.8 mmol/L), confirming co-existing EDKA. Results: Following empagliflozin discontinuation, targeted treatment with concurrent insulin–dextrose infusion resulted in complete resolution of acid-base imbalance within five days. Conclusions: A concurrent surgical complication appeared to mask EDKA and contributed to a delay in its recognition. In patients receiving SGLT-2 inhibitors, metabolic acidosis that persists after an apparent surgical cause has been addressed should prompt measurement of serum ketones, irrespective of the blood glucose concentration. Structured perioperative protocols for SGLT-2 inhibitor management and postoperative ketone surveillance may help to prevent similar events. Full article

Background: Diabetic ketoacidosis (DKA) remains a preventable yet frequent complication at the onset of type 1 diabetes (T1D) in children, driven by delayed symptom recognition, socioeconomic disparities, and inconsistent access to care. Early identification of presymptomatic T1D through autoantibody-based screening, together with emerging disease-modifying therapies, may reduce the incidence of DKA. This review synthesizes evidence on epidemiology, risk determinants, screening strategies, and immunological interventions relevant to DKA prevention. Methods: A narrative review was conducted using PubMed, EMBASE, Scopus, Web of Science, and Google Scholar (2011–2026). Eligible sources included clinical studies, guidelines, systematic reviews, meta-analyses, and prevention trials addressing staging, screening, epidemiology, and disease-modifying treatments in pediatric T1D. Landmark publications outside this timeframe were included when essential. Evidence was integrated to identify determinants of DKA and strategies to reduce its occurrence. Results: DKA risk is influenced by younger age, socioeconomic disadvantage, rural residence, misdiagnosis, and limited access to specialized care. Sustained public awareness and community-based education reduce DKA incidence, whereas short-term campaigns show transient effects. Structured screening programs, including TrialNet and TEDDY, demonstrate near-elimination of DKA among monitored children. Teplizumab delayed progression from stage 2 to stage 3 T1D by a median of approximately 24 months in the original TN-10 trial, with extended follow-up demonstrating a median delay of 32.5 months. It is approved for individuals with stage 2 T1D aged ≥ 1 year and has recently gained approval for selected patients with newly diagnosed T1D, expanding opportunities for early disease modification. Global networks such as INNODIA strengthen prevention through coordinated biomarker-driven research. Conclusions: Reducing DKA at T1D onset requires integrated, sustained strategies combining public awareness, systematic autoantibody screening, structured follow-up, and access to emerging immunotherapies. Coordinated care across primary providers, pediatric endocrinologists, and research networks is essential to advance a proactive, prevention-oriented model of pediatric T1D care. Full article

Background and Objectives: This retrospective study evaluated patients with diabetes classified according to cluster-derived diabetes phenotype groups and compared their baseline metabolic characteristics, documented complication profiles, and HbA1c course during follow-up. Materials and Methods: A total of 158 patients with type 1 or type 2 diabetes followed at Zonguldak Bülent Ecevit University Endocrinology Outpatient Clinic were included. Phenotype assignment was based on baseline domains corresponding to the Ahlqvist framework: age at diagnosis, BMI category, HbA1c, beta-cell function, insulin resistance, and autoantibody status. Complications were not used for phenotype assignment. Baseline characteristics, binary complication status, exploratory phenotype-contrast logistic regression, and longitudinal HbA1c data were evaluated. Results: The groups showed significant differences in age, age at diagnosis, HbA1c, obesity status, fasting glucose, C-peptide, fasting insulin, HOMA1-%B, HDL cholesterol, ALT, and eGFR. Hepatic steatosis/suspected NAFLD, retinopathy, nephropathy, polyneuropathy, and ketosis/ketoacidosis differed among groups when complications were analyzed as ever-positive versus negative. In exploratory phenotype-contrast logistic regression, Clusters 3–4 were associated with hepatic steatosis/suspected NAFLD, Cluster 2 with retinopathy and polyneuropathy, Cluster 3 with nephropathy, and Clusters 1–2 with ketosis/ketoacidosis; the contrast for coronary artery disease did not reach statistical significance. In a linear mixed-effects model for repeated HbA1c measurements, phenotype group was associated with HbA1c levels, whereas the time effect and group-by-time interaction were not statistically significant. Conclusions: Cluster-derived diabetes phenotype groups showed distinct baseline metabolic characteristics and different documented complication profiles. These findings should be interpreted as exploratory because of the retrospective design and incomplete follow-up data. Full article

Background and Objectives: Electronic glycemic management systems (eGMSs) are increasingly used to guide intravenous insulin infusion for hospitalized patients with diabetic ketoacidosis (DKA), but available comparative evidence remains non-randomized and clinically heterogeneous and includes multiple algorithmically distinct platforms. Methods and Materials: We conducted a systematic review and meta-analysis in accordance with PRISMA guidance and a prospectively registered protocol (PROSPERO: 2025 CRD420251019614). Seven non-randomized studies comprising 3874 hospitalized patients were included; six studies contributed data to the primary meta-analysis of time to DKA resolution. The primary outcome was time to DKA resolution. Secondary outcomes included ICU length of stay (LOS), hospital LOS, duration of insulin infusion, and hypoglycemia (mild and severe). Random-effects models were applied. Results: Six studies contributed to the primary meta-analysis of time to DKA resolution; across the review, seven studies included 3874 patients. The pooled analysis showed no statistically significant difference between groups (SMD −0.04, 95% CI −0.22 to 0.14; I² = 74.8%). Recorded hypoglycemia was lower among patients managed with eGMS; however, these estimates should be interpreted cautiously because of heterogeneity, serious-to-critical risk of bias, and potential differences in glucose-monitoring and documentation practices. ICU and hospital LOSs and duration of insulin infusion showed no statistically significant differences overall, with heterogeneity across studies. Conclusions: In available non-randomized evidence, eGMS-guided insulin infusion was not associated with a clear difference in time to DKA resolution, ICU length of stay, hospital length of stay, or insulin infusion duration compared with conventional protocols. Lower recorded hypoglycemia was observed with eGMSs, but this finding should be considered hypothesis-generating because of serious-to-critical risk of bias, residual confounding, substantial heterogeneity, and possible detection bias. High-quality randomized trials or target trial emulation studies are needed before recommending widespread adoption, as certainty of evidence was very low across all outcomes. Full article

Background/Objectives: Omnipod 5 is a tubeless automated insulin delivery system integrating continuous glucose monitoring (CGM) with algorithm-driven insulin delivery. Clinical trials and real-world studies have shown improved glycemic control and reduced hypoglycemia in people with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI) or non-automated sensor-augmented pump (SAP) therapy. However, long-term real-world data in young adults remain limited. Methods: We conducted a retrospective, single-centre observational study including adults with T1D who started therapy with a tubeless automated insulin delivery system (Omnipod 5). Participants were previously treated with MDI or SAP therapy. Glycemic outcomes were assessed using CGM metrics at baseline, 1, 3, and 12 months after starting the system. The primary outcome was change in time in range of 70–180 mg/dL (TIR) at 12 months. Secondary outcomes included additional CGM metrics, insulin therapy parameters, and the occurrence of diabetic ketoacidosis (DKA) and severe hypoglycaemia (SH) episodes. Results: Fifty-two patients were included (mean age 23.0 ± 4.3 years; diabetes duration 13.8 ± 5.9 years); 51 completed 12-month follow-up. At 12 months, TIR increased from 56.1 ± 11.4% to 67.4 ± 11.0% (+11.3%; p < 0.001), while time in tight range of 70–140 mg/dL (TITR) increased from 34.5 ± 10.9% to 44.8 ± 8.7% (+10.3%; p < 0.001). Time in hypoglycemia also decreased, with no episodes of DKA or SH reported during the study period. Glycemic improvements were evident at 1 month and maintained at 12 months. The proportion of patients achieving recommended targets improved at 12 months, including TIR > 70% (13.5% to 43.1%). Total daily insulin requirements remained unchanged, while basal insulin proportion increased, and daily boluses decreased (both p < 0.001). Conclusions: In this real-world study, Omnipod 5 therapy was associated with improved glycemic control and reduced hypoglycemia over 12 months in young adults with T1D, without increasing insulin requirements. Full article

A ketogenic diet (KD) is a low-carbohydrate, high-fat dietary approach. Beyond treating neurologic disorders, KDs have attracted significant media attention for their potential to improve obesity and diabetes. The diet induces a metabolic shift from glucose toward fatty acid oxidation and ketone body production. This shift leads to ketosis, which may reduce hunger, partly through the anorexigenic effects of ketone bodies, thereby contributing to weight loss and improved metabolic parameters, including glycaemic control and insulin sensitivity. In particular, the positive effects of KDs lower insulin demand and may thereby improve β-cell function. However, the long-term efficacy, safety, and sustainability of KDs, especially for diabetes, remain debated. This review offers current insights into the effects of ketogenesis and ketosis, as well as the potential mechanisms underlying them. We explore the metabolic effects of KDs in obesity and diabetes, drawing on preclinical and clinical studies, and suggest that combining KDs with antidiabetic agents may provide synergistic benefits. However, combining KDs with these pharmacotherapies, particularly SGLT-2 inhibitors, requires careful clinical supervision because of potential risks, including euglycaemic diabetic ketoacidosis. We explore how a KD alters the composition of the gut microbiota, thereby affecting host health. We conclude by highlighting challenges and future directions for optimising KD-based therapies and by outlining the limitations of the current review. Full article

Diabetes mellitus is a complex metabolic disorder whose management has moved from glycemic control to the control of risk factors through the use of new antihyperglycemic drugs with pleiotropic effects. Despite the multiple cardio–renal benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors, their prescription is often avoided due to concerns regarding side effects. This review aims to discuss the multiple benefits of SGLT2 inhibitors in balance with one of the most concerning side effects, the risk of euglycemic diabetic ketoacidosis (EDKA). A literature search was performed to identify and select articles relevant to this topic. We accessed several databases, including PubMed, Web of Science and Scopus, using appropriate keywords. We selected and evaluated randomized controlled trials, retrospective studies, systematic reviews and meta-analysis published between 2014 and 2024 supporting the multifaceted benefits of SGLT2 inhibitors and the limitations of their recommendations and focusing on the risk of EDKA. Initially designed as antidiabetic agents, SGLT2 inhibitors have demonstrated important cardio–renal benefits, these drugs being the first-line medication in patients with established cardiovascular disease, heart failure and chronic kidney disease. SGLT2 inhibitors are associated with some potential side effects, but with contradictory data concerning their prevalence and clinical relevance. From the possible side effects, EDKA is a life-threatening metabolic emergency whose incidence and recognition has increased, in particular with the use of SGLT2 inhibitors. These drugs can cause this disorder through several mechanisms, including reduced insulin secretion and increased glucagon levels, leading to free fatty acid production, which generally occurs in the presence of some risk factors such as reduced dietary carbohydrates, intercurrent illnesses, surgical stress and alcohol consumption. Through awareness of these risk factors as well as of the clinical symptoms, this condition could be promptly avoided or managed and SGLT2 inhibitors could be safely used. Full article

Background: Kidney transplant recipients (KTRs) with diabetes mellitus (DM) are at high cardiovascular risk, and heart failure (HF) is a major concern. Dapagliflozin has proven benefits in HF, but data in KTRs are scarce. Methods: Retrospective analysis of adult KTRs with DM and HF who received dapagliflozin. Data were collected at baseline, defined as dapagliflozin initiation, and at the most recent follow-up (April 2024). Outcomes included changes in LVEF, renal function, metabolic and hemodynamic parameters, hospitalizations, and adverse events. Results: In 32 KTRs (median age 60.5 years, 66% male), after a median follow-up of 2.2 years, left ventricular ejection fraction (LVEF) did not change significantly (60% to 58%, p = 0.28). Systolic BP decreased by 5 mmHg (p < 0.001) and diastolic BP by 3 mmHg (p = 0.034). HbA1c decreased from 7.3 [6.6–8.1] to 6.8 [6.3–7.7]% (p = 0.034), while LDL-c and triglycerides decreased (p = 0.013 and p < 0.001). Body weight and BMI also decreased (both p < 0.001). Renal function, as assessed by eGFR, remained stable (p = 0.633), with no major renal safety signals. No deaths, severe hypoglycemia, or ketoacidosis occurred; urinary tract infections in 12%. Conclusions: In this exploratory cohort, dapagliflozin use was followed by stable graft function and changes in metabolic and hemodynamic parameters. No significant change in LVEF was observed. Given the observational design, small sample size, limited echocardiographic data, and absence of a control group, causal inference is not possible. These hypothesis-generating findings require confirmation in prospective controlled trials of KTRs with diabetes and heart failure. Full article

Background: The pharmacological management of type 2 diabetes mellitus has become increasingly complex due to expanding therapeutic options and the high prevalence of multimorbidity in affected patients. As a result, the risk of drug–drug and drug–disease interactions has grown significantly, with potential implications for glycemic control, safety, and treatment outcomes. Objective: This narrative review provides a comprehensive, class-based overview of clinically relevant interactions associated with antidiabetic medications, highlighting their mechanisms, clinical consequences, and practical management strategies. Methods: A targeted literature search was conducted using major medical databases to identify clinical studies, meta-analyses, pharmacovigilance reports, and evidence-based guidelines concerning interactions related to key antidiabetic drug classes. Interactions were categorized as pharmacokinetic, pharmacodynamic, or disease-related. Results: Significant variability exists across antidiabetic drug classes in terms of interaction profile and clinical relevance. Metformin presents interaction risks mainly through renal impairment or co-administration with drugs affecting lactate metabolism. Sulfonylureas and glinides are strongly associated with hypoglycemia-enhancing interactions. DPP-4 inhibitors generally exhibit a low interaction burden, whereas GLP-1 receptor agonists may interact through delayed gastric emptying. SGLT2 inhibitors require caution in patients with diuretics or conditions predisposing them to dehydration or ketoacidosis. Insulin remains highly sensitive to pharmacodynamic interactions with a broad spectrum of therapies. Underlying renal, hepatic, and cardiovascular conditions further modify the interaction risk. Conclusions: Understanding class-specific interaction profiles is essential for personalized and safe diabetes management. Careful medication review, close metabolic monitoring, and individualized dose adjustments can mitigate the risk of harmful interactions. Further research is needed to elucidate interactions in populations with advanced multimorbidity and polypharmacy. Full article

A 65-year-old man with type 2 diabetes presented with abdominal pain. Although he had no typical reflux symptoms such as heartburn or acid regurgitation, esophagogastroduodenoscopy (EGD) showed findings suggestive of reflux esophagitis, and proton pump inhibitor therapy was initiated. Two months later, he was admitted with intractable vomiting. EGD demonstrated diffuse circumferential mucosal injury without black discoloration, predominantly in the distal esophagus. These findings were interpreted as severe reflux esophagitis (Los Angeles grade D; RE-D). Symptoms improved with supportive care, glycemic control, and continued PPI therapy; follow-up EGD showed marked improvement. Six months later, he re-presented with identical symptoms and endoscopic findings. Laboratory testing confirmed diabetic ketoacidosis (DKA), with ketonuria, elevated total ketone bodies (2469 µmol/L), and high-anion gap metabolic acidosis (anion gap 17.2 mEq/L). The diagnosis was revised to DKA-associated acute esophageal mucosal lesion (AEML). He improved with fluid resuscitation and insulin therapy, and medication adherence was reinforced. Follow-up EGD showed complete healing without recurrence. AEML has been proposed as a spectrum that includes acute esophageal necrosis (AEN; “black esophagus”) and esophagitis without black-appearing mucosa. This case highlights a diagnostic pitfall in which DKA-associated AEML without black discoloration may be misattributed to severe reflux esophagitis. When the clinical presentation or endoscopic appearance is severe or atypical, clinicians should consider AEML and evaluate for underlying systemic precipitants. Full article

Background: Evidence supports the effectiveness and safety of open-source automated insulin delivery (AID) in patients with type 1 diabetes. However, evidence regarding the clinical application of open-source AID in perioperative patients with type 2 diabetes remains limited. Methods: This was an open-label, single-center, exploratory pilot randomized controlled trial (RCT) with parallel groups. Patients with diabetes (excluding type 1 diabetes mellitus) scheduled for elective surgery were randomly assigned to the closed-loop group (open-source hybrid closed-loop AID system) or the control group (conventional insulin pump). The primary outcome was the percentage of time in the target glucose range (TIR, 3.9–10.0 mmol/L). Other efficacy and safety outcomes were also compared between the groups. Results: A total of 49 participants were included and randomized to the closed-loop group (n = 25) or the control group (n = 24). Participants underwent abdominal, orthopedic, thoracic surgery, or neurosurgery during hospitalization. Patients in the closed-loop group had significantly higher TIR than patients in the control group (76.4 ± 14.1% vs. 61.2 ± 20.0%, p = 0.005). Compared with the control group, the closed-loop group also exhibited a 15.6 percentage point reduction in time above range (TAR, >10 mmol/L) without increasing time below range (TBR, <3.9 mmol/L). There were no episodes of severe hypoglycemia (<2.2 mmol/L) or diabetic ketoacidosis in either group. Conclusions: This study demonstrates that in patients with diabetes undergoing elective surgery, the open-source hybrid closed-loop AID system provides better glycemic control than conventional insulin pump therapy. Full article

Mucormycosis, triggered by fungi of the order Mucorales, represents a potentially fatal invasive mycosis, with death rates over 50% despite intensive therapy. The COVID-19 pandemic brought a sharp increase in cases, especially in individuals with diabetes mellitus and those undergoing immunosuppressive treatment, emphasizing significant gaps in our comprehension of disease pathogenesis. Emerging molecular studies have highlighted key virulence factors, such as the CotH family of invasins that facilitate endothelial invasion via interaction with glucose-regulated protein 78 (GRP78), complex iron acquisition systems necessary for fungal growth, and the release of mucoricin, a ricin-like toxin that impairs vascular integrity. Host defense depends mainly on innate immunity, with neutrophils and macrophages working as critical effector cells, while adaptive Th1 and Th17 responses aid in the fungal removal. Mucorales use a variety of immune evasion techniques, such as pathogen-associated molecular pattern (PAMP) masking via cell wall transformations, resistance to phagocytic death, and metabolic utilization of host factors including hyperglycemia and increased free iron in diabetic ketoacidosis (DKA). This review summarizes current evidence of the molecular processes underlying mucormycosis pathogenesis, underscoring host–pathogen interactions at the cellular and molecular levels, immune evasion tactics, and translational potential for new diagnostic and therapeutic approaches. Comprehending these molecular processes is crucial for creating efficient therapies against mucormycosis in an era of growing immunocompromised patients and expanding infectious disease synergies. Full article