Search Results (1,195)

Background/Objectives: Bipolar disorder affects about 40 million people worldwide, and the greatest burden of the disease is associated with depressive episodes. About 25% of patients experience drug-resistant depression, in which standard treatment turns out to be insufficient, and monotherapy often does not bring full remission. Despite the use of second-generation antipsychotics, the effectiveness of therapy in TRBD remains limited, which necessitates rational polypharmacotherapy and augmentation strategies. The paper discusses the receptor mechanisms of drug combination, current therapeutic regimens and new interventions such as ketamine acting on the glutamate anergic system. The aim was to synthetically compare the efficacy and safety of available augmentation strategies and polypharmacotherapy. Methods: The material consists of published clinical, observational and randomized trials on pharmacotherapy of drug-resistant bipolar depression, including atypical neuroleptics, ketamine, pramipexole, modafinil, lamotrigine, celecoxib and memantine. The authors analyze receptor mechanisms, neurobiological data and clinical trial results, comparing them with current definitions of TRBD according to ISBD and CINP. Biomarker data, such as the Systemic Immune-Inflammation Index, and the results of neuroimaging and metabolomic studies were also used in the work. Results: The analysis showed that atypical neuroleptics showed limited efficacy and high rates of side effects, while ketamine has the fastest and most pronounced antidepressant effect with a low risk of phase change. Pramipexole has shown promise in terms of long-term efficacy, but its use reduces the high risk of induction of mania and impulse control disorders. Celecoxib as an anti-inflammatory therapy significantly increased response and remission rates compared to escitalopram alone, and memantine showed only an early, short-term antidepressant effect. The results highlight that TRBD requires targeted polypharmacotherapy, with the most promising directions being glutamatergic modulation and anti-inflammatory therapies. Conclusions: Drug-resistant bipolar depression requires a departure from classical monotherapy in favor of rational, mechanistically justified polypharmacotherapy, targeting complex monoaminergic, glutamatergic and neuroinflammatory disorders. Available data indicate that ketamine has the greatest clinical potential among the current strategies, characterized by a rapid onset of action and a favorable safety profile compared to atypical neuroleptics or dopamine agonists. Modulation of inflammatory processes with the use of celecoxib also has promising results, which highlights the importance of biomarkers and personalization of therapy. However, further, large, and well-designed studies are needed to unambiguously determine optimal treatment strategies for TRBD and to verify the effectiveness of new pharmacological interventions. Full article

Background/Objectives: Psychotic relapse affects over 80% of individuals with schizophrenia-spectrum disorders, driving long-term disability and hospitalization. Clinical relapse management relies on symptomatic monitoring without objective neurobiological tools to guide individualized antipsychotic decisions. Methods: This systematic review synthesizes evidence on neurophysiological, blood-based, molecular, neuroimaging, and digital biomarkers for relapse prediction in schizophrenia-spectrum disorders. Results: Following the PRISMA 2020 guidelines, five databases were searched through March 2026 for longitudinal biomarker studies. Quality was assessed using the Newcastle-Ottawa Scale and PROBAST; findings were synthesized narratively due to substantial heterogeneity. From the 6812 citations screened, 21 studies were included across clinical high-risk, first-episode, and established illness populations. Conclusions: Mismatch negativity and P300 event-related potential (P300) showed the most consistent associations with relapse vulnerability, with mismatch negativity demonstrating relative independence from antipsychotic effects. Inflammatory and neuroendocrine markers—interleukin-6, C-reactive protein, and cortisol awakening response—predicted poor treatment response in multiple longitudinal investigations. Peripheral blood gene expression profiling identified TCF4 network dysregulation as a candidate molecular marker of impending relapse. Neuroimaging models did not outperform standard clinical variables. Digital phenotyping showed ecological promise but remains methodologically nascent. No single biomarker achieves sufficient accuracy for clinical implementation. Neurophysiological and inflammatory markers are the most tractable candidates for monitoring protocols. Future research should prioritize multimodal longitudinal designs, external validation, and systematic antipsychotic confounding control. Among the biomarkers reviewed, mismatch negativity and the interleukin-6/cortisol awakening response combination represent the most tractable candidates for pilot clinical implementation, particularly in specialized early psychosis services and antipsychotic dose-reduction research contexts; no biomarker currently achieves sufficient accuracy for routine use in maintenance treatment decisions. Full article

Emerging evidence implicates the gut–brain axis in the pathophysiology of schizophrenia, yet literature regarding specific microbiome alterations remains inconsistent. This study aims to synthesize evidence on gut microbiota diversity and taxonomic composition in individuals with schizophrenia compared to healthy controls. Unlike prior meta-analyses, this study integrates quantitative alpha diversity synthesis with cross-taxonomic qualitative analysis and contextualizes findings within functional frameworks of the gut–brain axis, highlighting the methodological heterogeneity that limits biological interpretation. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. Electronic databases (Web of Science, PubMed, MDPI) were searched for observational studies published between 2017 and 2025. Forty-eight studies met inclusion criteria for qualitative synthesis, with 14 providing sufficient data for random-effects meta-analyses of alpha diversity. Meta-analyses revealed no statistically significant differences in alpha diversity indices (Shannon, Simpson, Chao1, ACE, Observed) between patients and controls, despite high heterogeneity. Conversely, beta diversity analyses generally demonstrated significant differences in microbial community composition. Taxonomic synthesis identified recurrent but heterogeneous dysbiotic patterns characterized by the depletion of short-chain fatty acid-producing taxa (e.g., Faecalibacterium, Roseburia, Lachnospiraceae) and enrichment of pro-inflammatory taxa (e.g., Proteobacteria, Fusobacterium). Schizophrenia is associated with evidence of compositional alterations and functional shifts rather than a global loss of microbial richness. These findings highlight candidate taxa that may warrant further investigation in biomarker-focused studies and microbiome-based therapeutics. However, these findings should be interpreted cautiously due to substantial heterogeneity and limited control for key confounders such as antipsychotic medication, diet, and life-style factors. Full article

Heat waves have intensified since the 1960s, leaving older adults uniquely susceptible to heat-related illnesses, including hyperthermia and fluid-electrolyte imbalances. While clinicians recognize that certain medications increase heat vulnerability, the specific interplay between drug use and patient characteristics remains unclear. This scoping review, following the Joanna Briggs Institute framework for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, investigated the risk of heat-related illness associated with medication use in older adults to identify research gaps. Investigators queried four databases for English-language primary literature (2000–2025) based on predefined Population, Concept, and Context criteria. Additionally, a grey literature search mapped existing United States (U.S.) mitigation strategies. Two reviewers independently screened studies via Covidence, and one extracted data. Results included 61 primary studies and 41 grey literature sources. While epidemiological data confirm higher heat-related morbidity and mortality in older populations, few experimental studies evaluate medication’s specific role. Despite many public health efforts, specific, evidence-based guidance on managing drug-heat interactions is limited. Diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), anticholinergics, and antipsychotics were the medication classes most frequently associated with heat-related illness. This review underscores a critical need for research into the confluence of age, multimorbidity, and polypharmacy to inform future clinical mitigation and protect vulnerable populations. Full article

Tardive dyskinesia (TD) is a persistent hyperkinetic movement disorder associated with prolonged dopamine D2 receptor blockade, particularly during chronic haloperidol (HP) exposure. Emerging evidence suggests that TD-like pathology is sustained by an interconnected redox–mitochondrial–inflammatory network within striatal circuits; however, the regulatory architecture of this network remains incompletely defined. Hyperoside (HS), a flavonol glycoside with cytoprotective properties, has been implicated in cellular stress-response modulation, yet its role in antipsychotic-induced motor dysfunction remains unclear. In this study, a six-group mechanistic design was employed in which rats received HP (1 mg/kg, i.p., 21 days) to induce TD-like orofacial dyskinesia (OD), quantified by vacuous chewing movements (VCMs) and tongue protrusions (TPs). HS (30 mg/kg, i.p.) was administered alone or in combination with HP, with or without pharmacological inhibition of nuclear factor erythroid 2–related factor 2 (Nrf2) using ML385. HP exposure induced progressive dyskinetic behavior accompanied by oxidative and nitrosative stress, mitochondrial dysfunction, increased pro-inflammatory cytokines, and elevated caspase-3 activity in the striatum. HS significantly attenuated behavioral abnormalities while restoring redox balance, preserving mitochondrial enzyme activities, and reducing inflammatory and apoptotic signaling. Notably, Nrf2 inhibition intensified molecular pathology without proportionally worsening behavioral outcomes, indicating a dissociation between biochemical vulnerability and overt motor expression. Furthermore, ML385 markedly attenuated HS-mediated protection across multiple endpoints. Collectively, these findings support a potential protective role for Nrf2-related regulatory mechanisms in limiting network destabilization in TD-like pathology, while highlighting the importance of integrated stress-response pathways in modulating disease progression. Full article

Background: Data on early changes in body composition during acute-phase treatment in adolescents with major depressive disorder (MDD) remain limited. In particular, the utility of novel anthropometric indices reflecting central and visceral adiposity has not been explored in this population. This study therefore aimed to examine short-term clinical outcomes alongside detailed anthropometric measures in drug-naïve adolescent inpatients receiving fluoxetine-based pharmacotherapy. Methods: Prospective, clinician-directed, non-randomized inpatient study. Drug-naïve adolescents with severe MDD (n = 23) received fluoxetine 20 mg/day, with some patients additionally receiving low-dose quetiapine (100 mg/day) based on clinical indication for six weeks. Depressive symptomatology was evaluated by questionnaires Montgomery–Åsberg Depression Rating Scale (MADRS) and Children’s Depression Inventory (CDI). Conventional and novel anthropometric indices (BMI, WHtR; BRI, AVI, ABSI, BAI) were examined using the objective bioimpedance-derived method for body composition. Results: Depressive symptom severity decreased over the six-week treatment period, with significant improvements observed on both MADRS and CDI (time effect p < 0.001). Response and remission rates increased over time in the overall sample. No statistically significant changes were observed in conventional or novel anthropometric indices across the study period. Conclusions: In this prospective pilot cohort of adolescent inpatients with MDD, six weeks of fluoxetine-based pharmacotherapy was associated with improvement in depressive symptoms. No short-term changes were observed in anthropometric indices; however, given the small sample size and limited follow-up, these findings should be interpreted cautiously and cannot be considered definitive evidence of cardiometabolic safety. Full article

Background/Objectives: This study aimed to evaluate the frequency and predictors of adverse drug events (ADEs) related to medication abuse, misuse, and dependence, along with serious adverse events (SAEs), and to develop machine learning models to detect serious abuse, misuse, and dependence cases. Methods: This study included 455,415 ADE reports involving medications with high dependence potential reported to the Korea Adverse Event Reporting System (KIDS KAERS DB) between 2013 and 2022. Multivariate logistic regression was used to identify predictors. Three machine learning algorithms, random forest (RF), support vector machine, and eXtreme Gradient Boosting, were developed and evaluated. Results: Higher reporting likelihood of abuse-, misuse-, and dependence-related ADEs was observed with concomitant use of acetaminophen (OR 3.60, 95% CI 2.40–5.39), antidepressants (OR 1.75, 95% CI 1.17–2.61), antipsychotics (OR 4.97, 95% CI 3.21–7.17), and anticonvulsants (OR 3.42, 95% CI 2.42–4.81). Reports from the general public were associated with higher odds of abuse, misuse, and dependence than those from healthcare professionals (OR 4.59, 95% CI 3.04–6.94). Ketamine (ROR 14.03) and bromazepam (ROR 13.02) showed the highest likelihood of being classified as SAEs. Cardiovascular (ROR 30.36) and respiratory disorders (ROR 17.03) demonstrated the highest SAE reporting likelihood. RF model demonstrated the best predictive performance (AUC-ROC 0.928; accuracy 94.4%), with reporter type identified as a key feature. Conclusions: RF model demonstrated optimal predictive performance, with reporter type as the most important feature for detecting serious cases. This study emphasizes the importance of incorporating patient-reported data and polypharmacy surveillance to facilitate early detection of serious cases. Full article

Background: In recent years, case reports and case series have suggested an association between the use of second- (SGAs), but not first-generation antipsychotics (FGAs), also known as atypical and typical APDs, respectively, and hyperglycemic complications, notably diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). Although this evidence is informative, there is a need for more observational studies to strengthen this body of knowledge. Objective: To conduct a systematic review of evidence established in observational studies on adverse drug events, specifically DKA and HHS, associated with the use of FGAs and SGAs. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using appropriate index phrases and keywords through October 17, 2025. Exposure included at least one United States Food and Drugs Administration (US FDA)-approved antipsychotic drug (APD); outcomes were limited to DKA and HHS. Results: A total of 15 observational studies were included in this review, including seven analytical and eight descriptive studies. These studies varied in scope and used different case definitions, study populations, exposures, and outcomes. The observational studies support existing evidence of an association between atypical APDs and DKA, mainly. As a class, typical APDs were associated with an increased risk of DKA, when compared to non-antipsychotic drug use. Although some studies evaluated this association in relation to HHS, there is insufficient information to draw conclusions for this outcome at this time. Conclusions: This analysis provides additional evidence of an association between use of atypical APDs and DKA. Additional analytical studies using administrative health databases are needed to clarify this association. Full article

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by a progressive clinical course and associated with a wide range of gene transcription signatures. This review examined studies retrieved from PubMed (published between 2005 and 2025) that investigated transcription factors (TFs) correlated with SCZ. Approximately 150 studies aligning with the eligibility criteria were selected. The synthesized evidence identified more than 40 TFs implicated in the pathogenesis and risk of SCZ. Based on functionality, these TFs were categorized into four groups: (1) progenitor cell TFs (TCF4, POU3F2, NKX2.1, EGR3), (2) stem cell TFs (MYC, SOX2, ASCL1, REST, NR2E1), (3) metabolic reprogramming TFs (HIF1, SREBPs, STATs, SOX9, NRF1, NRF2, p53, FOXO, ATF4, NF-κB), and (4) nuclear TFs (AhR, RXR). The discussion shed light on how these TFs in consort with hundreds of potential genes could shape the pathophysiology of SCZ. Indeed, SCZ represents a complex genomic, nuclear, metabolic, and immune disorder characterized by a diseased cellular microenvironment, with hypoxia emerging as a key feature. Although targeting TFs pharmacologically remains challenging, innovative therapeutic strategies—such as antineoplastic and antipsychotic agents that modulate the cellular microenvironment—may offer promising new directions for SCZ treatment. Full article

Background: Sexual dysfunction is a frequent adverse effect of antipsychotic treatment and a major contributor to poor adherence and reduced quality of life. Evidence regarding the impact of switching to prolactin-sparing antipsychotics in routine clinical practice remains limited. This study evaluated changes in sexual function following initiation or switch to cariprazine in real-world patients with schizophrenia spectrum disorders. Methods: In this prospective observational study, adult outpatients were either initiated on cariprazine de novo (Group A) or switched from a previous antipsychotic due to clinically significant sexual dysfunction (Group B). Sexual function was assessed using the Psychotropic-Related Sexual Dysfunction Questionnaire (SALSEX) at baseline and Month 3. Secondary measures included serum prolactin levels and Brief Psychiatric Rating Scale (BPRS) an CGI scores. Effect sizes were calculated using Cohen’s d. Results: Forty-two patients were included (Group A: n = 14; Group B: n = 28). In Group B, mean SALSEX total scores significantly decreased from 8.04 ± 2.76 to 2.41 ± 2.06 (Δ = −5.63; p < 0.001; d = 2.27). Prolactin levels also significantly decreased after switching (p = 0.012). In Group A, SALSEX scores showed a statistically significant but clinically modest reduction (2.79 ± 2.01 to 1.23 ± 1.24; p = 0.023; d = 0.93), with no evidence of treatment-emergent sexual dysfunction. Improvements in sexual function were not associated with changes either in BPRS or CGI scores, baseline symptom severity, sex, or testosterone levels. Conclusions: Switching to cariprazine in patients with antipsychotic-related sexual dysfunction was associated with large and clinically meaningful improvement in sexual function in routine practice. The effect appeared independent of overall symptom improvement and endocrine normalization thresholds, supporting the clinical value of prolactin-sparing switching strategies. Full article

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and its co-occurrence with psychiatric disorders poses significant therapeutic challenges. This narrative review examines the safe use of psychopharmacological agents in patients with HF, focusing on mood stabilizers (particularly lithium) and antipsychotics. We summarize clinically relevant pharmacokinetic and pharmacodynamic interactions between these agents and guideline-directed HF therapies, including ACEIs, ARBs, ARNIs, beta-blockers, MRAs, SGLT2 inhibitors, and diuretics. Lithium is particularly prone to interactions due to its narrow therapeutic index and dependence on renal sodium handling, with RAAS inhibitors, thiazide diuretics, and SGLT2 inhibitors increasing the risk of toxicity. Antipsychotics are associated with QT prolongation, orthostatic hypotension, and electrolyte disturbances, with substantial variability between agents. This review highlights key clinical risks, provides a practical summary of drug interactions, and outlines principles for individualized, multidisciplinary management. Care requires coordinated cardiology–psychiatry collaboration, careful drug selection, and assessment of renal function, electrolytes, drug levels, and ECG parameters. Further studies and improved guideline integration are needed. Full article

Background: Autonomic side effects are a major determinant of tolerability for many psychotherapeutic drugs. While often attributed to receptor-mediated mechanisms, the potential contribution of direct modulation of smooth muscle excitability remains poorly characterized at a comparative pharmacological level. Methods: A systematic comparative pharmacological profiling of a broad panel of psychotherapeutic drugs (antidepressants, antipsychotics, and anxiolytics) was conducted using a standardized ex vivo model. Potassium chloride (KCl, 105 mM) was used to induce depolarization-dependent contraction in three isolated smooth muscle preparations (rat uterus, rat vas deferens, and guinea-pig ileum). Inhibitory potency (IC₅₀), dose-dependency, and tissue consistency were integrated to define functional inhibitory profiles. Results: Psychotherapeutic drugs exhibited marked heterogeneity in their ability to inhibit K⁺-induced smooth muscle contraction. Integrative analysis stratified compounds into four distinct functional profiles: (i) High Inhibitory Liability (e.g., nortriptyline, paroxetine), characterized by low micromolar IC₅₀ values and dose-dependent inhibition across multiple tissues; (ii) Non-Selective Inhibition (e.g., flunarizine, cinnarizine), showing consistent but dose-independent inhibition; (iii) Tissue-Dependent Inhibition (e.g., risperidone, reboxetine); and (iv) Minimal Inhibition (e.g., moclobemide). Agents classified within the High Inhibitory Liability profile correspond to drugs known to carry a higher clinical burden of autonomic adverse effects. Conclusions: This study reveals a previously underrecognized pharmacodynamic dimension of psychotherapeutic drugs and establishes a comparative functional taxonomy based on their direct, non-receptor-mediated inhibition of smooth muscle excitability. The identified profiles provide a mechanism-informed framework for contextualizing autonomic side-effect liability and may support improved safety evaluation in psychotherapeutic drug development. Full article

Background: Post-psychotic depression (PPD) is an underestimated but clinically significant affective syndrome that occurs during remission from psychosis, particularly in schizophrenia. Material and Methods: This comprehensive review traces the evolution of this concept over five decades of research, starting from its initial differentiation from primary depression and schizoaffective disorders in the 1970s. Relying on more than thirty studies, we analyze historical definitions, biological and psychosocial mechanisms, diagnostic controversies, and therapeutic implications. Results: Research indicates that PPD develops from multiple contributing factors, including psychological insight, autobiographical disturbances, pharmacological influences, and social losses, rather than simply as a byproduct of psychosis or pharmacological treatment. We discuss the persistence of depressive symptoms after acute remission, their role in suicidal tendencies, and the diagnostic challenges arising from the overlap of negative symptoms and demoralization. Despite its exclusion from current diagnostic standards, PPD continues to affect a significant fraction of patients, particularly those with high insight and early onset. Conclusions: Effective treatment requires a multidimensional, phase-specific approach combining antidepressants, atypical antipsychotics such as lurasidone, and psychological interventions targeting identity, self-esteem, and narrative processing. We argue that PPD should be reintroduced as a distinct clinical unit and incorporated into psychiatric guidelines to reduce diagnostic oversights and improve patient outcomes. Full article

Introduction: Antipsychotic (AP) medications are widely prescribed beyond psychotic disorders, yet their long-term safety profile regarding breast cancer (BC) risk remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating the association between AP exposure and incident BC. Eligible studies reported adjusted odds ratios (ORs) with 95% confidence intervals for any AP, prolactin-increasing antipsychotics (PIAPs), or prolactin-sparing antipsychotics (PSAPs). Study quality was assessed using the modified Newcastle-Ottawa Scale (mNOS), and certainty of evidence was graded with the GRADE framework. Random-effect models were used to pool effect estimates by exposure category, duration, and cumulative Defined Daily Dose (DDD). Results: Nine high-quality observational studies encompassing 108 effect estimates were included. Most studies achieved mNOS scores of 9, yet GRADE certainty ranged from very low to moderate, with the overall body of evidence graded as low certainty due primarily to residual confounding. Any AP exposure was associated with a modestly increased BC risk, particularly with long-term use: use for >5 years yielded pooled ORs around 1.5–1.6, while short-to-medium duration (1–5 years) showed smaller increases (pooled ORs in the range 1.2–1.3). For PIAPs, both longer duration (>5 years) and higher cumulative exposure (>1000–2000 DDDs) were consistently associated with ORs/HRs in the 1.3–1.6 range, suggesting a possible dose–response pattern. Histological analyses indicated stronger associations for ductal than lobular BC, and elevated risks were observed across age strata, including women aged <55 and ≥70 years. Discussion: This meta-analysis suggests that chronic exposure to prolactin-increasing antipsychotics is associated with a potentially clinically relevant increase in BC risk, whereas prolactin-sparing agents do not show a clear signal of harm. However, the certainty of this association is limited by inconsistently measured confounders and by the observational nature of the data. These findings support a cautious, individualized approach in which clinicians preferentially consider PSAPs when appropriate, discuss BC risk as part of shared decision-making, and integrate tailored screening strategies for women requiring long-term PIAP therapy. Further high-quality pharmacoepidemiologic studies with better confounder control and mechanistic integration are needed to refine risk estimates and inform preventive neuropsychopharmacology. Full article

Background/Objective: In recent years, epidemiological and clinical evidence has suggested an association between the use of second-generation antipsychotics (SGAs) and hyperglycemic complications: notably, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). However, the role of first-generation antipsychotics (FGAs) remains less well understood. To conduct a systematic review of evidence established in case reports (CRs) on adverse drug reactions, specifically DKA and HHS, associated with the use of both FGAs and SGAs in order to identify patterns that may inform clinical awareness and future research. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using index phrases and keywords up until 17 October 2025. Eligible CRs discussed exposure to at least one US FDA-approved antipsychotic drug (APD) and assessed either DKA or HHS. Results: A total of 151 CRs were included in the systematic review (DKA, n = 121; HHS, n = 28; both conditions, n = 2). Patients aged 30 to 39 years accounted for the highest number of emergencies (n = 49, 32.5%), which occurred mostly in males (n = 108, 71.5%). The most common mental health diagnosis was schizophrenia (n = 77, 51%), followed by bipolar disorder (n = 26, 17.2%). Olanzapine was associated with the highest number of DKA cases (n = 53, 43.1%), followed by clozapine (n = 24, 19.5%). The average blood glucose at presentation was 842.8 mg/dL for DKA patients and 1252.8 mg/dL for HHS patients. The average hemoglobin A1c levels (HbA1c) were 11.5% and 12%, respectively, for these two conditions. Of the 12 reported fatalities, treatment with olanzapine was noted in four DKA cases and in one HHS case. Conclusions: This analysis provides additional evidence of an association between the use of atypical APDs and DKA or HHS. Clinicians should continue to monitor metabolic risk factors for these conditions, as well as educating patients about the prevention of acute diabetic complications. Full article