Untreated Diabetes Mellitus Research Articles

A Study of Abnormal Echocardiogram Findings in Patients With Chronic Kidney Disease With Reference to Cardiac Biomarkers.

Background Chronic kidney disease (CKD) isprevalent, especially in populations with multiple risk factors, such as undiagnosed and untreated hypertension and diabetes mellitus. Cardiovascular diseases (CVDs) leading to poor quality of life or even death have been noted as an increasing trend among CKD patients. This study aims to use cardiac biomarkers to evaluate their association with abnormal echocardiogram findings in CKD patients, which may allow for the improvement of quality of life with early treatment. Methods and materials This observational, cross-sectional study was conducted on 103 diagnosed CKD patients at the Department of Medicine, Dr. D.Y. Patil Medical College, Hospital, and Research Centre in Pimpri, Pune, from January 2023 to January 2024. Ethical approval was acquired, and written consent was obtained from participants. The study utilised cardiac biomarkers such as N-terminal pro-B type natriuretic peptide (NT-proBNP), troponin I (Trop I), and a radiological tool, transthoracic echocardiography (TTE). All patients with diagnosed stages 3, 4, and 5 CKD between the ages of 18-80 years were included, and the exclusion criteria consisted of patients who had already undergone cardiac interventional procedures or known cases of CVDs. Results In our study, out of 103 participants, the majority were aged between 51 and 60 years (35, 34%). The study had a majority of male participants (76, 73.8%). Major risk factors were considered, noting hypertension in 63 (61.2%) and diabetes mellitus in 81(78.6%). Participants were divided into stages of CKD. Cardiac biomarkers such as NT-proBNP and Trop I levels were assessed in all participants in the different stages of CKD showing elevated levels of NT-proBNP across all stages. Transthoracic echocardiogram (TTE) screening tests were also evaluated for all patients, showing diastolic dysfunction (DD) as the most common finding in stage 3 (5, 41.67%), stage 4 (25, 62.5%), and stage 5 (35, 68.83%), followed by left ventricular hypertrophy (LVH) as a common finding in stage 3 (4, 33.3%), stage 4 (20, 50%), and stage 5 (30, 58.2%) CKD. Furthermore, the association between raised cardiac biomarkers and abnormal echocardiogram findings across the stages of CKD was evaluated, resulting in a statistically significant association with p-values < 0.05. Conclusion This research sheds light on the association between cardiac biomarkers and abnormal echocardiogram findings in CKD patients and helps us determine if there is any added benefit orpredictive value in screening these individuals at different stages of the disease to allow early interventionand improvement in treatment and quality of life.

Severe Hypertriglyceridemia in a Child with Refractory, Fatal Diabetic Ketoacidosis: A Case Report with Review of Literature

Background: Diabetic ketoacidosis (DKA) is an acute life-threatening complication of diabetes. Dyslipidemia due to disturbance in glucose metabolism can cause elevation in serum triglyceride levels. Severe hypertriglyceridemia is a complication of DKA, rarely reported in children. Clinical Description: A 3-year-old girl, newly diagnosed, but untreated type 1 diabetes mellitus (DM), presented with DKA. The first blood sample showed serum as grossly milky, with highly raised levels of triglyceride (2170 mg/dL) and cholesterol (791 mg/dL). Many of the blood parameters were erroneous due to the lipemic sample. Serum amylase and lipase were normal, ruling out pancreatitis. Management and Outcome: Correction of dehydration, insulin infusion, antibiotics, and vasopressor support were started. Despite treatment with insulin and supportive care, the patient had a rapidly deteriorating course and ultimately succumbed to the illness. Conclusion: Uncontrolled, untreated DM in a child can result in decompensated DKA, which is usually associated with severe hypertriglyceridemia, and a rapidly progressive fatal course.

Antidiabetic properties of Tarchonanthus camphoratus in fructose-induced diabetic Wistar rats

Tarchonantus camphoratus (TC) has been used traditionally to manage diabetes mellitus (DM) in Kenya but its efficacy has not been scientifically evaluated. This study aimed at evaluating the antidiabetic properties of TC crude leaf extract in diet-induced diabetic Wistar rats. DM was induced using high fructose (25% w/v) in drinking water for 12 weeks. Rats were divided into five groups (n=7): Groups I: normal control; II; diabetic untreated; III, IV &amp; V; diabetic treated (21 days) with metformin (100 mg/kg.bw/day), 300 and 600 mg/kg.bw/day of TC extract respectively. Fasting body weights and blood glucose levels were monitored weekly. Oral glucose tolerance test, serum lipid profile, creatinine, urea, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins (TP), C-reactive protein (CRP), albumin (ALB) and triglyceride (TG) mass in skeletal muscle were analysed at end of the study. Qualitative phytochemical analysis was done using standard procedures. Diabetic untreated rats had significantly higher body weights (p ˂0.05) compared to other groups. There was a significant reduction in fasting blood glucose in TC treatment groups compared to untreated controls. Increased glucose tolerance was observed in treated groups. TC extract significantly improved fructose-induced hypertriglyceridemia compared to DM groups. ALP, ALT, and CRP were significantly lowered while TP and ALB were elevated in the extract treated rats compared with untreated DM rats. DM group also exhibited significantly higher skeletal muscle TG mass when compared to normal control and diabetic treated groups. The phytochemical-rich TC leaf extract therefore possess potential alternative medicine for DM management.

Socio-economic inequalities in undiagnosed, untreated, and uncontrolled diabetes mellitus in Bangladesh: is there a gender difference?

ObjectivesWe aimed to determine: (1) the prevalence and socio-economic distribution of undiagnosed, untreated, and uncontrolled diabetes mellitus (DM); (2) the relationship between socio-economic status (SES) and undiagnosed, untreated, and uncontrolled DM; and (3) if this relationship is mediated by gender. Study designCross-sectional nationally representative household-based survey. MethodsWe used data from the Bangladesh Demographic Health Survey from 2017 to 18. Our findings were based on the responses of 12,144 individuals aged 18 years and older. As a measure of SES, we focused on standard of living (hereinafter referred to as wealth). The study's outcome variables were prevalence of total (diagnosed + undiagnosed), undiagnosed, untreated, and uncontrolled DM. We used three regression-based approaches—adjusted odds ratio, relative inequality index, and slope inequality index—to assess different aspects of SES differences in the prevalence of total, undiagnosed, untreated, and uncontrolled DM. We used logistic regression analysis to look at the adjusted association between SES and the outcomes after gender stratification to see whether gender status moderates the association between SES and the targeted outcomes. ResultsIn our sample analysis, the age-adjusted prevalence of total, undiagnosed, untreated, and uncontrolled DM was 9.1%, 61.4%, 64.7%, and 72.1%, respectively. Females had a higher prevalence of DM and undiagnosed, untreated, and uncontrolled DM than males. When compared to people in the poor SES group, people in the rich and middle SES groups had 2.60 times (95% confidence interval [CI] 2.05–3.29) and 1.47 times (95% CI 1.18–1.83) higher chance of developing DM. When compared to individuals in the poor SES group, those in the rich SES groups were 0.50 (95% CI 0.33–0.77) and 0.55 times (95% CI 0.36–0.85) less likely to have undiagnosed and untreated DM. ConclusionsIn Bangladesh, rich SES groups were more likely than poor SES groups to have DM, whereas poor SES groups with DM were less likely than rich SES groups to be aware of their disease and obtain treatment. The government and other concerned parties are urged by this study to pay more attention to developing suitable policy measures to reduce the risk of DM, particularly among rich SES groups, as well as targeted efforts to screen for and diagnose DM in socio-economically disadvantaged groups.

Incidence and Outcomes of Undiagnosed and Untreated Diabetes Mellitus in Trauma Patients.

Diabetes is a major determinate for mortality in trauma patients. Many diabetics are undiagnosed or poorly controlled. Trauma patients disproportionately come from lower socioeconomic status, making missed diagnoses more likely. We aimed to quantify the incidence of undiagnosed or poorly controlled diabetics assessed at a Level 1 Trauma Center. We did a retrospective chart review of admitted trauma patients over a one-month period. Past Medical History, home medication lists, and Hemoglobin A1c on admission were recorded for each patient. We determined that 30 of 173 trauma patients qualifying for the study were diabetic. Furthermore, 30% of these diabetics were undiagnosed or had poorly controlled diabetes. Undiagnosed pre-diabetics made up 20% of the entire study group. Our data show that 26% of trauma patients would benefit from an intervention for improved glucose control. Trauma centers should consider creating routine clinical practice guidelines to identify at-risk patients and provide intervention for long-term management.

Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study.

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

Undiagnosed Diabetes Mellitus in Acute Coronary Syndrome (ACS) Patients

Introduction: Diabetes mellitus is a significant precursor of CAD. Patients hospitalised for suspected myocardial infarction had type 2 diabetes at higher rates than the general population, increasing the likelihood of cardiovascular complications. Hospitalized individuals with CAD have a worse prognosis if they also have diabetes mellitus. Objective: With this study, we want to quantify the prevalence of unrecognised diabetes mellitus among Acute Coronary Syndrome patients at a tertiary care hospital in Lahore. Study design: Cross sectional study Setting: Department of Cardiology, Bahria Town Hospital, Lahore Duration: Six months (09-2018 to 03-2019) Data collection procedure: One hundred forty patients who fulfilled the study's inclusion and exclusion criteria were included. Using a standardised questionnaire, we were able to collect information such as age, gender, and type of ACS (STEMI, Non-STEMI, or unstable angina). Diabetes was diagnosed by measuring fasting blood sugar and haemoglobin A1c in a serum sample of 3 cc. It was noted that untreated diabetes mellitus was present. Results: There were 110(78.6%) males and 30(21.4%) females in our study. The mean age of patients was 57.08±12.72 years. The mean height was 171.95±14.37 cm, mean weight was 80.70±11.23 kg and mean BMI was 26.89±3.64. There were 63(45%) patients with family history of diabetes. There were 60(42.9%) patients with Non-STEMI, 52(37.1%) with STEMI and 28(20%) with unstable angina. The mean HbA1c of the patients was 6.11±0.86. There were 10(7.1%) patients with undiagnosed Diabetes mellitus. Conclusion: 7 percent of ACS patients have diabetes mellitus that has not been diagnosed. Keywords: Undiagnosed Diabetes Mellitus, Acute Coronary Syndrome, type 2 diabetes, family history, STEMI,

Sleep disorders and increased risk of dementia.

Sleep disorders and increased risk of dementia.

A metacognitive confidence calibration (MCC) tool to help medical students scaffold diagnostic reasoning in decision-making during high-fidelity patient simulations.

The purpose of this study was to 1) help novice students scaffold problem-solving and engage safely in the deliberate practice of diagnostic reasoning and medical decision-making in real time; 2) assess how accurately students gather and apply data in medical reasoning and treatment during high-fidelity patient simulations (HFPSs); 3) identify students' scientific misconceptions related to the case; 4) promote student metacognitive processing, self-assessment, and self-efficacy; and 5) facilitate the explicit calibration of student confidence in deliberate reasoning with patient outcomes. In a mixed-method design, a metacognitive calibration self-assessing (MCC) survey tool was applied to HFPS (n = 80, 20 teams of 6 medical students) and semistructured interviews were conducted with faculty (n = 5). When scored by faculty with a rubric, the mean student accuracy ranged from 23% to 74%, whereas their self-assessment of confidence ranged from 71% to 86%. This result revealed overconfidence bias in novice students regarding the correctness of their wrong responses. The most common misconception identified was inverting cause and effect: metabolic acidosis was pointed to as the cause of the patient's problems rather than a consequence of untreated diabetes mellitus. The most common treatment error was overtreatment, with unnecessary added medication. Interviews with faculty suggested that the MCC tool improved the team process by slowing students down, requiring them to think through their answers, and that overall the tool improved their critical thinking. This study demonstrated the feasibility of using a metacognitive confidence calibration tool to assist novice students in learning safely to make deliberate diagnostic reasoning and decisions on patient care in real time during complex simulations while observing objectively their levels of psychological confidence against patient outcomes.NEW & NOTEWORTHY This study demonstrates the feasibility of a metacognitive confidence calibration tool (MCC) to assess and promote novices in the learning of diagnostic reasoning and treatment decisions on patient care in real time during high-fidelity patient simulations while comparing confidence and accuracy data and identifying students' scientific misconceptions. Results revealed the presence of overconfidence bias, overtreatment, and the misconception of metabolic acidosis as the cause of the patient's problems rather than a consequence of untreated diabetes mellitus.

Abstract 123: Insulin resistance syndrome presenting with diabetic ketoacidosis – A rare case presentation

Background: Insulin Resistance Syndrome (IRS) occurs either due to mutation or auto-antibodies to insulin receptor. Presentation as diabetic ketoacidosis (DKA) although rare has been reported in few case reports. We report a young male presenting with DKA with very high insulin requirement.Case Presentation: A 17-year-old male, with untreated diabetes mellitus diagnosed at 12 years of age, presented with vomiting and kussmaul breathing. On examination he was emaciated, had short stature; severe acanthosis nigricans and hypertrichosis. At admission, his plasma glucose was 470 mg/dl, HCO3 6 mEq/L with positive ketones. He was diagnosed as severe DKA and treated with insulin with dose requirement of 120 units/day for adequate glycemic control. GAD-65 antibodies were negative and he had dyslipidemia but no organomegaly. Genetic test was sent for a suspicion of insulin resistance or lipodystrophy which showed homozygous mutation in INSR gene previously described in Rabson Mendenhall syndrome. The child was treated with insulin, metformin and pioglitazone.Conclusion: Type 1 DM is the most common etiology for DKA. But in patients with very high insulin requirement and signs of insulin resistance, possibility of IRS should be kept and genetic testing offered.

Abstract 49: Insulin resistance syndrome presenting with diabetic ketoacidosis – A rare case presentation

Background: Insulin Resistance Syndrome (IRS) occurs either due to mutation or auto-antibodies to insulin receptor. Presentation as diabetic ketoacidosis (DKA) although rare has been reported in few case reports. We report a young male presenting with DKA with very high insulin requirement.Case Presentation: A 17-year-old male, with untreated diabetes mellitus diagnosed at 12 years of age, presented with vomiting and kussmaul breathing. On examination he was emaciated, had short stature; severe acanthosis nigricans and hypertrichosis. At admission, his plasma glucose was 470 mg/dl, HCO3 6 mEq/L with positive ketones. He was diagnosed as severe DKA and treated with insulin with dose requirement of 120 units/day for adequate glycemic control. GAD-65 antibodies were negative and he had dyslipidemia but no organomegaly. Genetic test was sent for a suspicion of insulin resistance or lipodystrophy which showed homozygous mutation in INSR gene previously described in Rabson Mendenhall syndrome. The child was treated with insulin, metformin and pioglitazone.Conclusion: Type 1 DM is the most common etiology for DKA. But in patients with very high insulin requirement and signs of insulin resistance, possibility of IRS should be kept and genetic testing offered.

Short-Term Treatment of Metformin and Glipizide on Oxidative Stress, Lipid Profile and Renal Function in a Rat Model with Diabetes Mellitus

Background: Oxidative stress, lipid profile and renal functions are well-known conventional risk factors for diabetes mellitus (DM). Metformin and gliclazide are popularly used monotherapy drugs for the treatment of DM. Aims: This study aims to assess the short-term treatment of single and dual therapy of glipizide/metformin on oxidative stress, glycemic control, serum lipid profiles and renal function in diabetic rats. Methods: DM was induced in rats with streptozotocin (STZ), then five different treatments were applied, including group I (untreated healthy control), group II (diabetic and untreated), group III (diabetic and treated with metformin), group IVI (diabetic and treated with glipizide) and group V (diabetic and treated with a combination of metformin and glipizide. Lipid peroxidation (LPO), nitric oxide (NO), total antioxidant capacity (TAC), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and urea were measured. Results: Compared to the untreated DM group, FBG and HbA1c were significantly reduced in the DM groups (p &lt; 0.01) treated with metformin (159.7 mg/dL &amp; 6.7%), glipizide (184.3 mg/dL &amp; 7.3%) and dual therapy (118 mg/dL &amp; 5.2%), respectively. Treatment with dual therapy and metformin significantly decreased LPO and NO levels but increased TAC in diabetic rats more than glipizide compared to untreated diabetic rats. Furthermore, metformin (19.8 mg/dL, p &lt; 0.001), glipizide (22.7 mg/dL, p &lt; 0.001), and dual therapy (25.7 mg/dL, p &lt; 0.001) significantly decreased urea levels in the treated rats compared to untreated DM rats (32.2 mg/dL). Both drugs and their combination exhibited a substantial effect on total cholesterol, HDL, LDL and atherogenic index. Conclusions: These results suggest that the therapeutic benefits of metformin and glipizide are complementary. Metformin exhibited superior performance in improving glycemic control and decreasing oxidative stress, while glipizide was more effective against dyslipidemia. These findings could be helpful for the treatment of future vascular patients, antilipidemic medicines and antioxidant therapy to improve the quality of life.

Docking-based virtual screening, ADMET, and network pharmacology prediction of anthocyanidins against human alpha-amylase and alpha-glucosidase enzymes as potential antidiabetic agents

Diabetes mellitus (DM) characterized by high blood sugar concentration is a major global public health problem and untreated DM results in blindness, kidney failure, heart attack, stroke, and lower extremity amputation. In this structure-based drug design (SBDD) study, the potential inhibitory effects of twelve anthocyanidins (aglycon unit of anthocyanins) components on human pancreatic α-amylase and intestinal α-glucosidase enzymes were investigated using the molecular docking method and a novel approach developed by our research group was used to rank the global binding potentials of ligands to a series of different enzymes simultaneously. In addition, drug-likeness, absorption-distribution-metabolism-excretion-toxicity (ADMET) predictions, and intracellular target-component interaction network analyses of twelve anthocyanidin components were performed using the search tool for interactions of chemicals (STITCH). Petunidin, peonidin, and aurantinidin were determined as 'hit' phytochemicals according to the docking binding energy and relative binding capacity index (RBCI) analyses, whereas, based on the RBCI index, petunidin was found to be the most effective ligand in terms of binding capacity to both enzymes that play an important role in DM. The more accessible and large-volume active site of α-amylase compared to α-glucosidase caused petunidin to bind with higher affinity against α-amylase. Promisingly, petunidin did not violate any of the criteria for drug-likeness consisting of a combination of the Lipinski's rule of 5, Ghose and Veber filters, showed no cytochrome (CYP) P450 or hERG I-II inhibitory activity in the ADMET analysis, however, it was found to have a low gastrointestinal absorption profile. In intracellular target-component network analysis using the STITCH online platform, it was determined that petunidin did not show negative functional interactions with any enzyme in the human protein network. Considering these results, it is recommended that petunidin be advanced to further in vitro and in vivo assays as a potential α-amylase and α-glucosidase inhibitory agent in the treatment of DM. However, the intestinal absorption profile of petunidin must be enhanced by molecular optimization without compromising its pharmacological activity.

Minimally invasive arthroscopic-assisted arthrodesis of the first metatarsophalangeal joint

Clinical and radiographic analysis of aminimally invasive arthrodesis technique of the first metatarsophalangeal joint. Symptomatic hallux rigidus, symptomatic hallux rigido-valgus, hallux varus. Absolute contraindication (CI): osteomyelitis; relative CI: untreated diabetes mellitus, smoking. Under arthroscopic assistance, aminimally invasive arthrodesis technique of the first metatarsophalangeal joint is performed with removal of the subchondral sclerosis and remaining cartilage of the osteoarthritic joint. Immediate weight-bearing starts on day1 using aready-made hallux valgus shoe for 6weeks. Physiotherapy without movement of the first metatarsophalangeal joint is allowed after surgery. Aseries of 5patients with symptomatic hallux rigidus and relevant medical diseases were evaluated after minimally invasive arthroscopic arthrodesis of the first metatarsophalangeal joint. In all cases osseous union was found after 8.4months. Follow-up was 22.6 months and the American Orthopedic Foot and Ankle Society (AOFAS) score increased significantly from 42.4 to 82.8 points. No complications requiring therapy were observed in our cohort nor was revision surgery necessary. The results of our series are in line with the published results of minimally invasive fusion techniques of the first metatarsophalangeal joint.

Potential of Hibiscus sabdariffa Linn. Polyphenol-Rich Extract in Improving Diabetes-Induced Vascular Functional and Structural Abnormalities in Rats

Hibiscus sabdariffa Linn. contains a high concentration of polyphenolic compounds and shows potentials in reducing vascular complications in diabetes mellitus (DM) patients. This study was aimed to determine the ability of H. sabdariffa Linn. polyphenol-rich extract (HPE) in improving vascular endothelial dysfunction and attenuating oxidative stress in type 1 DM. DM was induced in adult male rats and the rats were then divided into three groups; untreated DM (DM); DM with HPE supplementation (DM+HPE); and DM with metformin (DM+MET). Another group of non-diabetic rats served as the normal control group. These rats were left untreated for four weeks before being subjected to the supplementations for another four weeks. The thoracic descending aorta was isolated from the treated and untreated rats to measure the vascular reactivity, oxidative stress, and morphological alterations. The results showed that HPE supplementation significantly reduced the systolic blood pressure (SBP) and mean arterial pressure (MAP) in the DM+HPE group (p&lt;0.05). HPE also showed a tendency to improve endothelium-dependent vasorelaxation compared to the untreated diabetic rats. Rats treated with HPE exhibited a considerable improvement in the activities of antioxidants and significantly attenuated oxidative damage (p&lt;0.05). Histological findings showed that HPE supplementation improved morphological changes in the aorta. In conclusion, HPE supplementation reduces vascular abnormalities in DM condition probably via amelioration of oxidative stress.

Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions.

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

An implant-supported prosthetic rehabilitation of a patient with a bilateral subtotal maxillectomy defect secondary to rhino-orbital-cerebral mucormycosis: A clinical report of a graftless approach

This clinical report presents the rehabilitation of extensive hard and soft tissue defects caused by rhino-orbital-cerebral mucormycosis as a result of untreated diabetes mellitus. The patient underwent subtotal maxillectomy and was rehabilitated with an implant-supported maxillofacial prosthesis with zygomatic and pterygoid implants by following an immediate loading protocol.

The effect of cordycepin on brain oxidative stress and protein expression in streptozotocin-induced diabetic mice.

Diabetes mellitus (DM) is characterized by metabolic disorders and psychological deficits, including cognitive decline. Here, we investigated the effect of cordycepin on oxidative stress and protein expression in the brains of diabetic mice. Twenty-four mice were divided into four groups, one comprising untreated healthy mice (N); one comprising healthy mice treated with cordycepin (24 mg/kg body weight) (N+Cor); one comprising untreated DM mice; and one comprising DM mice treated with cordycepin (24 mg/kg body weight) (DM+Cor). After 14 days of treatment, cognitive behavior was assessed using the novel object recognition (NOR) test. The brain levels of oxidative stress markers (glutathione, catalase, and superoxide dismutase) were examined using the respective detection kits. Protein expression in brain tissues was assessed by liquid chromatography with tandem mass spectrometry (LC–MS/MS); the functions of the identified proteins were annotated by PANTHER, while major protein–protein interactions were assessed using STITCH. We found that cordycepin treatment significantly decreased body weight and food and water intake in the DM+Cor group compared with that in the DM group; however, no differences in blood glucose levels were found between the two groups. Cordycepin treatment significantly reversed cognitive decline in diabetic mice in the NOR test and ameliorated antioxidant defenses. Additionally, we identified ULK1 isoform 2, a protein associated with cognitive function via the activated AMPK and autophagic pathways, as being uniquely expressed in the DM+Cor group. Our findings provide novel insights into the cellular mechanisms underlying how cordycepin improves cognitive decline in diabetic mice.

Морфологические особенности эндокриноцитов поджелудочной железы крыс с сахарным диабетом 2-го типа при разной длительности терапии инкретиномиметиками

Группа препаратов, основанных на инкретиновых эффектах (аналоги глюкагоноподобного пептида-1 аГПП1) и ингибиторы дипептидилпептидазы-4, иДПП4), обладают способностью увеличивать репликацию β -клеток и ингибировать апоптоз. Инкретиномиметики способны влиять на функцию α-клеток, восстанавливая физиологическую регуляцию уровня глюкагона. При этом эффекты инкретиномиметиков на пролиферацию/апоптоз α-клеток изучены недостаточно. В единичных исследованиях отмечено увеличение пролиферации α-клеток, но факторы, определяющие выраженность этих изменений, не установлены. Цель - оценка влияния терапии инкретиномиметиками разной продолжительности на морфологические и функциональные особенности α- и β-клеток поджелудочной железы крыс (12 мес) с сахарным диабетом 2-го типа (СД 2-го типа). Методика. У крыс (возраст 12 мес), находящихся на высокожировой диете, моделировали стрептозотоцин-никотинамид-индуцированный СД 2-го типа. Животные получали инкретиномиметки: агонист рецепторов ГПП1 (лираглутид) или ингибитор ДПП4 (вилдаглиптин) в течение 4,10 и 24 нед. Макроскопически оценивали наличие/отсутствие видимых изменений поджелудочной железы. Парафиновые срезы поджелудочной железы окрашивали гематоксилином и эозином для оценки микроструктуры ткани. Проводили иммуногистохимическое (ИГХ) исследование с применением антител (Abcam) к глюкагону, инсулину в аппарате для ИГХ «Thermo Autostainer 720». После процедуры ИГХ ядра доокрашивали гематоксилином в аппарате для окраски гистологических микропрепаратов LeicaST5020. Результаты. Показано, что без лечения сахарный диабет приводил к снижению числа α- и β- клеток на всех сроках наблюдения. Лечение диабета лираглутидом и вилдаглиптином приводило к восстановлению пула как α-, так и β- клеток. При сравнении групп, получавших терапию и без терапии, с группой контроля значимые отличия сохранялись по количеству как α-, так и β-клеток во все сроки наблюдения. Через 4 нед в группах, получавших лираглутид, количество α-клеток стало сопоставимым с таковым в группе контроля, но количество β-клеток оставалось сниженным. После 10 и 24 нед терапии статистически значимой разницы между группой контроля и животными, получавшими терапию лиралутидом, по количеству как β-, так и α- клеток не выявлено. Заключение. Полученные данные свидетельствуют в пользу того, что терапия инкретиномиметиками способствует восстановлению пула как α-, так и β-клеток поджелудочной железы. Drugs based on incretin effects, including analogs of glucagon-like peptide-1 (GLP1) and dipeptidyl peptidase-4 inhibitors (DPP4), increase replication and inhibit apoptosis of β-cells. Incretin mimetics can influence the function of α-cells thereby restoring physiological regulation of glucagon. However, effects of incretin mimetics on proliferation and apoptosis of α-cells are understudied. A few studies reported increased α-cell proliferation, but the factors determining the degree of these changes were not established. Aim. To evaluate the effect of incretin mimetic treatment of different duration on morphological and functional features of pancreatic α- and β-cells of 12-month-old rats with type 2 diabetes mellitus. Method. Streptozotocin-nicotinamide-induced type 2 diabetes mellitus was modeled in 12-month-old rats receiving a high-fat diet. The rats were treated with incretin mimetics, a GLP-1 receptor antagonist (Liraglutide) or a DPP-4 inhibitor (Vildagliptin) for 4, 10 or 24 weeks. Paraffin sections of the pancreas were stained with hematoxylin-eosin to evaluate the tissue microstructure. An immunohistochemical (IHC) study was performed using glucagon and insulin antibodies (Abcam) with a Thermo Autostainer 720 IHC instrument. After the IHC procedure, nuclei were additionally stained with hematoxylin using a Leica ST5020 stainer for histological micropreparations. Results. Untreated diabetes mellitus resulted in decreased numbers of α- and β-cells at all timepoints of observation. The treatments with Liraglutide and Vildagliptin recovered the pools of α- and β-cells. Significant differences of both treated and untreated diabetic groups from the control group in the number of α- and β-cells remained at all timepoints of observation. In the Liraglutide group at 4 weeks, the number of α-cells became comparable with the control group, but the number of β-cells remained lower. At 10 and 24 weeks of treatment, statistically significant differences between the control group and the Liraglutide or Vildagliptin treatment groups in the number of α- and β-cells were not observed. Conclusion. The results of the study suggested that the incretin mimetic therapy provided recovery of both α and β-cell pools in the pancreas.

Burden of Undiagnosed Type 2 Diabetes in Diabetic Kidney Disease: A Japanese Retrospective Cohort Study.

The risk of developing diabetic kidney disease (DKD) in patients with undiagnosed diabetes mellitus (UD) has never been evaluated. We studied the burden of UD on the risk of developing DKD in the Japanese population in a single-center retrospective cohort study. The patients with type 2 diabetes mellitus, but without DKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or proteinuria), were recruited from January 2018 to January 2019; medical records were scrutinized retrospectively from January 2003 until May 2019. The individuals, with diabetes that could not be denied based on past and current records, comprised the undiagnosed diabetes (UD) group whereas those with confirmed diagnosis comprised the diagnosed diabetes (DD) group. The group differences were tested using a Kaplan–Meier curve and Cox proportional hazards model. Among the 408 participants, 164 (40.2%) and 244 (59.8%) comprised the DD and UD groups, respectively. The baseline parameters, including age, male gender, and BMI were comparable between the groups, but the plasma glucose, HbA1c levels, and diabetic retinopathy prevalence were higher in the UD group. The risk of developing DKD (log rank test, p < 0.001), an eGFR of < 60 mL/min/1.73 m2 (p = 0.001) and proteinuria (p = 0.007) were also higher in the UD group. The unadjusted and adjusted hazard ratios for DKD were 1.760 ((95% CI: 1.323–2.341), p < 0.001) and 1.566 ((95% CI: 1.159–2.115), p = 0.003), respectively, for the UD group. In conclusion, this is the first report showing that UD is a strong risk factor for DKD. The notion that a longer duration of untreated diabetes mellitus is involved strongly in the risk of developing DKD warrants the need for the identification and monitoring of UD patients.