Management Of Hyperglycemia Research Articles

Combined Administration of Metformin and Vitamin D: A Futuristic Approach for Management of Hyperglycemia.

Diabetes is a series of metabolic disorders that can be categorized into three types depending on different aspects associated with age at onset, intensity of insulin resistance, and beta- cell dysfunction: Type 1 and 2 Diabetes, and Gestational Diabetes Mellitus. Type 2 Diabetes Mellitus (T2DM) has recently been found to account for more than 85% of diabetic cases. The current review intends to raise awareness among clinicians/researchers that combining vitamin D3 with metformin may pave the way for better T2DM treatment and management. An extensive literature survey was performed to analyze vitamin D's role in regulating insulin secretion, their action on the target cells and thus maintaining the normal glucose level. On the other side, the anti-hyperglycemic effect of metformin as well as its detailed mechanism of action was also studied. Interestingly both compounds are known to exhibit the antioxidant effect too. Literature supporting the correlation between diabetic phenotypes and deficiency of vitamin D was also explored further. To thoroughly understand the common/overlapping pathways responsible for the antidiabetic as well as antioxidant nature of metformin and vitamin D3, we compared their antihyperglycemic and antioxidant activities. With this background, we are proposing the hypothesis that it would be of great interest if these two compounds could work in synergy to better manage the condition of T2DM and associated disorders.

Design, synthesis and anti-hyperglycemic assessments of novel 5-benzylidenethiazolidine-2,4-dione derivatives as PPAR-γ agonist

The treatment of diabetes mellitus still relies predominantly on peroxisome proliferator-activated receptor-γ (PPAR-γ) therapy, known for its effectiveness. In this present study, a novel series of benzylidene-linked thiazolidine-2,4-dione compounds was conceptualized, synthesized, and subjected to assessment for their potential antidiabetic properties. Notably, among the compounds examined, 5-((Z)-4-(((E)-Propylidene)amino)benzylidene)thiazolidine-2,4-dione, designated as 4c, emerged as the most promising candidate, exhibiting the highest PPAR-γ agonistic activity with an EC50 value of 0.35 ± 0.52 μM. Additionally, molecular docking investigations were conducted on twelve 2,4-thiazolidinedione compounds, with a pyrazole moiety incorporated, within the ligand binding domain of PPAR-γ. Compound 4c, in particular, demonstrated a Glide XP score of −9.104, surpassing the score of the crystal ligand (Glide XP score = −7.482). Notably, both exhibited similar interactions with key amino acids, including HIE323, SER289, and GLN286. Furthermore, three derivatives (4a-c) with promising PPAR-γ agonistic activity and favorable molecular docking scores underwent in vivo evaluation for their capacity to lower blood glucose levels using a streptozotocin-induced diabetic mice model. In comparison to the reference drug pioglitazone, Compound 4c displayed commendable in-vivo performance across multiple parameters, encompassing serum HDL, serum LDL, serum total cholesterol, and serum triglyceride levels. Molecular dynamics simulations provided insights into the impact of ligand 4c, indicating its role in enhancing protein stability and rigidity. These findings emphasize its potential as a potent protein inhibitor, thus opening novel avenues for the intelligent design of molecules with high efficacy in the management of hyperglycemia.

THU328 Appropriate Initial Insulin Dosage For Management Of Steroid-induced Hyperglycemia In Hospitalized COVID-19 Patients

Abstract Disclosure: N. Ketaroonrut: None. S. Kiertiburanakul: None. C. Sriphrapradang: None. Introduction: Steroid was recommended for the treatment of severe COVID-19 infection. There are limited studies on the management of steroid-associated hyperglycemia in hospitalized COVID-19 patients. We aimed to determine the appropriate initial insulin dosage to control hyperglycemia in hospitalized COVID-19 patients who received steroid therapy. Methods: We conducted a retrospective single-center analysis of electronic medical records of COVID-19 patients with steroid-induced hyperglycemia who had been treated with insulin. We divided the patients into 4 groups according to the total daily dose (TDD) of subcutaneous insulin therapy at the initiation of dexamethasone ≥6 mg/day or an equivalent dose of glucocorticoid. Glycemic outcomes were compared between groups. Results: A total of 156 patients [age 64±14 years; 50% men; body mass index 26.9±6.9 kg/m2; initial TDD of insulin (units/kg/day): group A, <0.29 (n=79); group B, 0.3-0.49 (n=33); group C, 0.5-0.69 (n=27); group D, >0.7 (n=17)] were included. Most patients (62%) had pre-existing type 2 diabetes. Mean admission blood glucose (BG) and HbA1c were 233±112 mg/dL and 7.8±2.3%, respectively. HbA1c was lowest in group A (6.7±1.2%) and highest in group D (9.8±2.5%). The average daily dexamethasone dosage or equivalent was 49.49±45.4 mg and there were no significant differences between the groups in the dexamethasone dose. The proportion of treatment failure (mean BG >280 mg/dL after the first day of insulin therapy or BG >400 mg/dL for at least 1 time/day) was lowest in group A. Among patients who received TDD >0.3 units/kg/day, group D had the lowest in both the percentage of treatment failure (B (52%) vs C (37%) vs D (29.4%), p=0.006) and mean BG during the 3 days of insulin therapy (B (246.0± 56.7 mg/dL) vs C (246.9±59.0 mg/dL) vs D (228.5±64.4 mg/dL), p=0.21). Three patients had severe hypoglycemia (BG <54 mg/dL) in this study (A: n=1 vs B: n=1 vs C: n=0 vs D: n=1, p=0.51). Conclusions: In the patients who require TDD >0.3 units/kg/day, the treatment failure of hyperglycemia was lowest in the patients who received TDD >0.7 units/kg/day without increasing severe hypoglycemia. This initial insulin dosage may guide physicians to achieve better glycemic control among hospitalized COVID-19 patients who received steroid therapy. Presentation: Thursday, June 15, 2023

THU250 Therapeutic Inertia In Primary Care With Poor Information Transfer To Specialist Care - A Rural Irish Experience

Abstract Disclosure: C.T. Coughlan: None. T.M. O'Sullivan: None. M.C. O'Donovan: None. M.J. Hannon: None. The burden of diabetes management in Ireland is shared between primary care physicans and specialists in secondary care, using current international management guidelines (1). However, long waiting lists and resource constraints limit the ability of secondary care to respond rapidly to all referrals. This study was designed to identify missed opportunities for early intervention in the management of diabetes in primary care. Written referrals of diabetes patients from primary care physicians to a specialist endocrinology service in a rural Irish hospital were audited to assess both the appropriateness of the referrals and to identify any missed opportunities for starting adjunctive treatments in primary care. We analysed all 74 referrals - mean age 58, 45% female – that were on the hospital diabetes clinic waiting list at the time of data collection. 61/74 (82%) had type 2 diabetes. The average time between date of referral and date of data collection was 231 days. Only 43/74 (58%) included a HbA1c value in the referral document. Of the type 2 diabetes referrals, only 12/61 (20%) included a BMI value. Mean HbA1c in the type 2 diabetes cohort was 71 mmol/mol (8.6%), and mean BMI was 30.6 kg/m2. Despite this, 19/61 (40%) were on monotherapy at time of referral, only 15/61 (25%) were on a GLP1 analog, and only 17/61 (28%) were on an SGLT2 inhibitor. Of the type 2 patients with documented BMI > 30 kg/m2, only 2/5 (40%) were on a GLP1 analog and only 2/5 (40%) were on an SGLT2 inhibitor. Lipid values were included in the referrals of 26/74 patients (35%), and blood pressure values in 25/74 (34%). Despite this, 44/74 (59%) were on a statin and 40/74 (54%) were on an ACE inhibitor or ARB. The renal function (serum creatinine or eGFR) was provided in 22/74 (30%), and information regarding microalbuminuria was provided in only 12/74 (16%). Foot examination was documented in 13/74 referrals (18%), and retinal screening status was documented in 17/74 (23%). Given the exponential increase in the numbers of patients with obesity and diabetes and increasing evidence on the importance of early multifactorial risk reduction, it is essential that cardiovascular risk factors and diabetes complications are documented and appropriate initial management commenced while patients await secondary care evaluation. Our study shows that referrals lack critical information which makes appropriate prioritization difficult. Also, the major classes of oral hypoglycaemic agents are under utilized in primary care, which exposes patients to damaging hyperglycaemia for an unnecessarily long time prior to secondary care evaluation. 1. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022;65(12):1925-66. Presentation: Thursday, June 15, 2023

SAT100 Management Of Post-exercise Hyperglycemia In A Patient Using Control IQ Artificial Pancreas System - A Case Report

Abstract Disclosure: P. Sharma: None. A. Ramirez Berlioz: None. Introduction: The automated insulin delivery (AID) Tandem Control IQ (CIQ) system has improved glycemic control with increased time in range (∼10%) & decreased hypoglycemic events (∼1%) through automatic basal rate modifications & correction bolus administration. The sleep & exercise activity (EA) decrease hypoglycemia risk. The CIQ EA decreases basal rate for predicted glucose =<140 mg/dl, increases basal rate for predicted glucose >160 mg/dl, and suspends insulin delivery for glucose =<80 mg/dl. It is designed for mild-moderate physical activity and is aggressive for high-intensity aerobic exercise or endurance training. High-intensity activity can cause post-exercise hyperglycemia. There is minimal data regarding management of post-exercise hyperglycemia when using AID systems. Case Report: A 40 year old female with uncomplicated type 1 diabetes mellitus managed by Tandem CIQ system reported post-exercise hyperglycemia after starting a new exercise routine. Previous routine included cardio and weight training on 4 days of the week. She had recently started a stationary cycling routine lasting 15-45 minutes with varying intensity. She would start the CIQ EA 1.5 hours prior to exercise and stop after completion. The pump report revealed hyperglycemia between 200-300 mg/dl occurring within 1 hour after exercise, lasting several hours after. Patient attempted using normal mode during exercise, manual bolusing immediately after exercise, and post-exercise insulin sensitivity factor modification without effect. Stopping EA 10-15 mins before completion led to elimination of post-exercise hyperglycemia. Discussion: The CIQ EA is designed to decrease exercise-induced hypoglycemia. After high-intensity exercise, the CIQ algorithm can exaggerate the hyperglycemia. High-intensity routines such as sprints, weight-lifting, intensive cycling, are associated with varying degrees of hyperglycemia. Our patient's new cycling routine was higher-intensity compared to what she previously did, leading to persistent hyperglycemia. Some recommendations to avoid post-exercise hyperglycemia in patients on AID systems include using CIQ normal mode during exercise, utilization of a temporary basal rate, or administration of a manual correction bolus. However, the use of normal mode or temporary basal rates can lead to glycemic variations during exercise. A manual correction bolus administered after exercise may be too late to avoid the hyperglycemia and leads to subsequent hypoglycemia due to enhanced insulin sensitivity post-activity. We tried stopping EA a few minutes before routine completion and found that 10 minutes was appropriate. We suggest that discontinuation of the EA 10 minutes before completion of exercise routine can alleviate post-exercise hyperglycemia. Additional studies are required to confirm whether this method would work on a larger scale. Presentation: Saturday, June 17, 2023

THU323 Extreme Insulin Resistance In Type 1 Diabetic After Covid 19 Infection

Abstract Disclosure: A.A. Zakkar: None. M. Fadanelli: None. M. Al Mushref: None. Patient is a 46-year-old African American female with a medical history of Diabetes Mellitus Type 1 for 20 years, hypothyroidism, rheumatoid arthritis and celiac disease who presented with a complaint of dizziness and heavy menstrual periods. When she presented, labs were significant for a glucose of 513 mg/dL, anion gap of 22 with a bicarbonate of 8, HbA1c of 10%, Hemoglobin of 8.1 and UA revealed ketones and she was thus started on an insulin drip for diabetic ketoacidosis. Patient was also complaining of a cough and weakness and thus a sputum sample was obtained which was positive for Streptococcus pneumoniae and she was started on antibiotics. At the time of arrival the patient was A&Ox4 and stated that her glucose has been really difficult to control over the last 6 months after she had been infected with COVID-19 and over that time she has also lost approximately 50 lbs. She stated that one month prior to the patient having COVID-19 infection, she was taking aspart 20 units per/meal and detemir 32 units qAM and 62 units qHS, and had an HbA1c of 8.5%. Just prior to presentation, the patient was taking 70 units of the U-100 aspart insulin per meal and 60 units of glargine U300 twice daily with persistent hyperglycemia. Insulin antibodies were tested and returned remarkably high. GAD-65 antibody was also high. The patient's glucose remained in the 500-600 mg/dL range and the acidosis worsened to a pH of 6.9 despite receiving continuous intravenous insulin aspart at 30units/hr with the addition of detemir 100 units q12-hours. The patient's acidosis resolved after two days and she was transitioned to Humulin R-U-500 at 80 units TID and aspart 40 units every 4-hours for tube feeding coverage but was still hyperglycemic in the 200-300 mg/dl range. Due to autoimmunity and extreme insulin requirements the patient was started on methylprednisolone 20 mg q8hr with improvement of glucose to the 150 to 200 mg/dl range and a decrease in her daily insulin requirements and thus she was transitioned to 60mg of prednisone daily with a 10mg taper weekly. By the time she was discharged 2 weeks later, her glucose was more controlled and her insulin requirements were decreased to aspart 14 units per/meal and detemir 40 units BID. Conclusion: In patients with diabetes mellitus who develop extreme insulin resistance following COVID -19 infection, consider autoimmune etiology in the differential diagnosis, such as insulin inactivating antibodies or insulin receptor blocking antibodies. In our experience laboratory testing of the specific antibodies was not available. Management of autoimmune mediated hyperglycemia will require immunosuppressivetherapy. Presentation: Thursday, June 15, 2023

THU054 A Post Hoc Analysis Of The Phase IV B2219 Study To Determine Predictive Factors For Hyperglycemia During Treatment With Pasireotide

Abstract Disclosure: S.L. Samson: Consulting Fee; Self; Novartis Pharmaceuticals, Chiasma. M. Bolanowski: Grant Recipient; Self; Amryt, Recordati, Pfizer, Inc., Novartis Pharmaceuticals, Ipsen, IBSA, Teva Pharmaceutical Industries Ltd., Berlin Chemie. Speaker; Self; Amryt, Recordati, Pfizer, Inc., Novartis Pharmaceuticals, Ipsen, IBSA, Teva Pharmaceutical Industries Ltd., Berlin Chemie. S. Zhang: None. Y. Yu: None. P. Witek: Grant Recipient; Self; Novartis Pharmaceuticals, Ipsen, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge), Lilly USA, LLC. Speaker; Self; Novartis Pharmaceuticals, Ipsen, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge), Lilly USA, LLC. N. Kietsiriroje: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. U. Feldt-Rasmussen: Advisory Board Member; Self; Novartis Pharmaceuticals, Recordati, Novo Nordisk, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Ipsen, Recordati, Novo Nordisk. Speaker; Self; Ipsen, Recordati, Novo Nordisk. Introduction: Pasireotide efficacy and safety in persons with acromegaly or Cushing’s disease (CD) is confirmed in a comprehensive clinical trial program. Pasireotide-induced hyperglycemia events, expected based on the drug’s mechanism of action, are manageable with low rates of treatment discontinuation. To advance knowledge on pasireotide-induced hyperglycemia management, a prospective randomized Phase IV study (B2219, NCT02060383) was conducted. This secondary analysis assessed factors that might predict development of pasireotide-induced hyperglycemia. Methods: In B2219, participants (Pts) with acromegaly or CD who did not need therapy for hyperglycemia or were managed with metformin alone entered the non-randomized observational arm. Pts who developed hyperglycemia not managed with metformin alone were randomized to incretin-based therapy or insulin. This analysis evaluated Pts according to whether therapy for hyperglycemia during pasireotide treatment was needed. Logistic regression analyses evaluated quantitative and qualitative predictive factors associated with pasireotide-induced hyperglycemia. Results: Of 190 Pts with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication during pasireotide treatment; Pt characteristics were generally balanced across subgroups at study baseline (BL). Most Pts who did not develop hyperglycemia had a mean age of <40 years (acromegaly 62.5%, CD 86.7%), BL glycated hemoglobin (HbA1c) <6.5% (acromegaly 98.9%, CD 100.0%) and BL fasting plasma glucose (FPG) <100 mg/dL (acromegaly 76.1%, CD 100.0%). Age (odds ratio [OR] 1.0, 95% CI 1.0−1.1), BL HbA1c (OR 3.5, 95% CI 1.3−9.9) and prediabetes or diabetes conditions (OR 3.0, 95% CI 1.2−7.6) were identified as risk factors associated with pasireotide-induced hyperglycemia in Pts with acromegaly. BL FPG (OR 1.2, 95% CI 1.0−1.3) was associated with increased risk of pasireotide-induced hyperglycemia in Pts with CD. Overall, adverse events (AEs) of hyperglycemia and diabetes mellitus (investigator reported) occurred in 21.1% and 14.2% of Pts with acromegaly and 28.8% and 11.9% of Pts with CD, respectively. More Pts who had diabetes or prediabetes conditions at BL had hyperglycemia-related AEs than Pts with normal glucose levels. Hyperglycemia-related AEs were managed with antihyperglycemic medication (acromegaly 26.3%, CD 30.5%); few Pts temporarily interrupted treatment (acromegaly 3.7%, CD 10.2%). Conclusions: These data suggest that age, HbA1c, FPG and having prediabetes or diabetes conditions at BL are associated with increased risk of developing pasireotide-induced hyperglycemia. AEs were manageable with antihyperglycemic medication. Potential risk factors associated with pasireotide-induced hyperglycemia may be used to identify Pts who need vigilant monitoring to ensure optimal outcomes during pasireotide treatment. Presentation: Thursday, June 15, 2023

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio < 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (<60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

THU372 Finasteride Induced Hyperglycemia

Abstract Disclosure: V. Bose: None. D.S. Martinez: None. Objective: Finasteride is a 5-alpha reductase inhibitor that is often prescribed to treat benign prostatic hyperplasia in men. It prevents the conversion of testosterone to dihydrotestosterone. Dihydrotestosterone has numerous physiological actions including having effects on physiological function of liver and pancreatic β-cells. While the medicine does not have hyperglycemia as an adverse effect on its profile, this is a case presentation of worsening hyperglycemia in a diabetic patient who was started on 5-alpha reductase inhibitor. Methods: The patient’s clinical course with laboratory data is presented. Results: The patient is a 69 year old obese male presented for hyperglycemia management. He had been treated with GLP1 agonist, SGLT2i and NPH. He noted that since starting finasteride in 2018, his fingerstick glucose levels were higher compared to prior readings. His hemoglobin A1c was also noted to have increased from 7% to 8.2%. He also reported some weight gain. Conclusion: In this case, one can see that the use of 5-alpha reductase inhibitor precipitated worsening hyperglycemia. The inhibition of androgens to their various metabolites may result in pathophysiological states that present as hyperglycemia via insulin resistance and liver disturbances. In patients with diabetes, the addition of finasteride or dutasteride should be cautiously monitored and if possible, avoided to limit worsening hyperglycemia and diabetic complications. Reference: Traish AM. Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It's Time to Sound the Alarm. World J Mens Health. 2020 Jul;38(3):323-337. doi: 10.5534/wjmh.200012. Epub 2020 Mar 20. PMID: 32202088; PMCID: PMC7308241. Presentation: Thursday, June 15, 2023

Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.

Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitiveand noncytotoxic inhibitor of α-glucosidase enzyme with half-maximal inhibitory concentration of 24.62±0.94μM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.

Inpatient glycemic management in noncritically ill patients: Updated guidelines.

Hyperglycemia is common in hospitalized patients and is traditionally managed with scheduled and correctional doses of insulin. The authors present an overview of the latest (2022) guidelines from the Endocrine Society on inpatient hyperglycemia management in noncritically ill patients, which includes a role for newer diabetes technologies and nontraditional insulin and noninsulin therapies.

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer.

The combination of fulvestrant with alpelisib, a PI3K inhibitor, improves progression-free survival in metastatic hormone receptor-positive, PIK3CA-mutant breast cancer. This study describes the incidence, risk factors, and treatment of alpelisib-associated hyperglycemia. Patients with metastatic breast cancer who received alpelisib from 2013 to 2021 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Alpelisib prescription dates and patient/tumor characteristics were abstracted from medical records. Risk factors associated with hyperglycemia and alpelisib dose reduction/discontinuation were evaluated using Pearson's χ2 tests. Among 247 patients, baseline median body mass index was 25.4kg/m2 and median hemoglobin A1c (HbA1c) was 5.5%. A total of 152 patients (61.5%) developed any-grade hyperglycemia and 72 patients (29.2%) developed grade 3-4 hyperglycemia; median time to onset was 16days. A total of 100 patients (40.5%) received alpelisib on a clinical trial; rates of hyperglycemia were significantly higher in patients treated as standard care versus on a clinical trial (any-grade hyperglycemia 80.3% vs. 34.0%, grade 3-4 hyperglycemia 40.2% vs. 13.0%, p<.001). Baseline HbA1c was significantly associated with development of hyperglycemia (p<.001) and alpelisib dose reduction/discontinuation (p=.015). Among those who developed hyperglycemia, 101 (40.9%) received treatment, most commonly with metformin. A total of 49 patients (19.8%) were referred to an endocrinologist, which was associated with SGLT2 inhibitor prescription (p=.007). Rates of hyperglycemia among patients treated with alpelisib as standard care were significantly higher than patients treated on clinical trials. Elevated baseline HbA1c is associated with alpelisib-induced hyperglycemia and requiring dose modification. Optimization of glycemic status before alpelisib initiation should become routine practice.

A study on clinical profile of diabetes mellitus in COVID-19 patients, hyperglycemia management, and risk assessment for mortality

A study on clinical profile of diabetes mellitus in COVID-19 patients, hyperglycemia management, and risk assessment for mortality

Identification of a Non-Invasive Urinary Exosomal Biomarker for Diabetic Nephropathy Using Data-Independent Acquisition Proteomics.

Diabetic nephropathy (DN), as the one of most common complications of diabetes, is generally diagnosed based on a longstanding duration, albuminuria, and decreased kidney function. Some patients with the comorbidities of diabetes and other primary renal diseases have similar clinical features to DN, which is defined as non-diabetic renal disease (NDRD). It is necessary to distinguish between DN and NDRD, considering they differ in their pathological characteristics, treatment regimes, and prognosis. Renal biopsy provides a gold standard; however, it is difficult for this to be conducted in all patients. Therefore, it is necessary to discover non-invasive biomarkers that can distinguish between DN and NDRD. In this research, the urinary exosomes were isolated from the midstream morning urine based on ultracentrifugation combined with 0.22 μm membrane filtration. Data-independent acquisition-based quantitative proteomics were used to define the proteome profile of urinary exosomes from DN (n = 12) and NDRD (n = 15) patients diagnosed with renal biopsy and Type 2 diabetes mellitus (T2DM) patients without renal damage (n = 9), as well as healthy people (n = 12). In each sample, 3372 ± 722.1 proteins were identified on average. We isolated 371 urinary exosome proteins that were significantly and differentially expressed between DN and NDRD patients, and bioinformatic analysis revealed them to be mainly enriched in the immune and metabolic pathways. The use of least absolute shrinkage and selection operator (LASSO) logistic regression further identified phytanoyl-CoA dioxygenase domain containing 1 (PHYHD1) as the differential diagnostic biomarker, the efficacy of which was verified with another cohort including eight DN patients, five NDRD patients, seven T2DM patients, and nine healthy people. Additionally, a concentration above 1.203 μg/L was established for DN based on the ELISA method. Furthermore, of the 19 significantly different expressed urinary exosome proteins selected by using the protein-protein interaction network and LASSO logistic regression, 13 of them were significantly related to clinical indicators that could reflect the level of renal function and hyperglycemic management.

Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications.

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body's antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes.

Exercise Prescription Principles among Physicians and Physical Therapists for Patients with Impaired Glucose Control: A Cross-Sectional Study.

Exercise confers a multitude of benefits with limited adverse side effects, making it a powerful "medication" for a plethora of diseases. In people living with uncontrolled glucose levels, exercise can be an effective "medication" to assist in the management of hyperglycemia. We sought to survey healthcare providers (physicians and physical therapists) to determine the current state of exercise recommendation for people with glucose control issues. Healthcare providers were surveyed from six academic medical centers in the Midwest to determine the recommended exercise parameters (type, frequency, duration, intensity, and timing) for patients with glucose control issues. Data from 209 practitioners who completed the survey were used for analysis. Chi-square tests were used to determine differences in exercise recommendations between physical therapists (PTs) and physicians (MD/DOs). PTs and MD/DOs recommended similar exercise parameters. Of all respondents, 78.9% recommended exercise to patients with glucose control issues. Respondents who considered themselves to be active exercisers were more likely to recommend exercise than those who were not exercisers. Only 6.1% of all respondents recommended post-meal exercise. Healthcare providers overwhelmingly recommended exercise for people with glucose control issues, but the "timing" is not congruent with best practice recommendations.

Evaluation of blood glucose changes with regular versus rapid-acting insulin for hyperglycaemia management in the emergency department.

As emergency department (ED) visits secondary to hyperglycaemia increase, goals should focus on optimising treatment to minimise the length of stay (LOS). Both regular and rapid-acting insulins can effectively treat hyperglycaemia, but have different pharmacokinetic profiles. The purpose of this study is to compare blood glucose (BG) reduction over time in patients receiving subcutaneous regular versus rapid-acting insulin in the ED. This retrospective chart review from 1 January 2018 to 31 December 2020 included adult ED patients with a BG ≥200 mg/dl who received subcutaneous regular insulin or insulin aspart. The primary endpoint was a change in BG immediately before and ≥30 min after insulin administration over time. There were 279 patients included in the study (108 regular insulin and 171 insulin aspart). Change in BG over time was 41.5 mg/dl/h in the regular insulin group and 47 mg/dl/h in the insulin aspart group (P = 0.36). There was no difference in hypoglycaemic events, ED LOS, time from insulin administration to discharge and total change in BG during ED stay. Patients who received regular insulin required less additional insulin doses (8.3% vs. 18.1%, P = 0.02), received a greater volume of intravenous fluids (1629 ml vs. 1280 ml, P = 0.02) and higher weight-based dose for the first insulin dose (0.11 units/kg vs. 0.10 units/kg, P = 0.02). There was no significant difference in BG reduction between insulin types for hyperglycaemic patients treated in the ED. This suggests that regular insulin and rapid-acting insulin have similar efficacy in the treatment of hyperglycaemia in the ED.

Long-term, real-world experience of pasireotide dose reduction in patients with acromegaly.

Pasireotide long-acting release is effective in achieving biochemical control and reducing tumour volume in patients with acromegaly inadequately controlled by first-line therapy. As part of a long-term, real-world study at our centre, 20 of 50 patients receiving pasireotide benefited from a reduction in pasireotide dose. Pasireotide reduced insulin-like growth factor I (IGF-I) levels to below the upper limit of the normal range, with some patients responding within 1-3 months of treatment (n=11) and others after ≥4 months (n=9). Following pasireotide dose reduction, IGF-I levels showed a mild increase but remained within the normal range after a median of 39 months in the early responders and 17 months in the late responders. Glucose and glycated haemoglobin levels decreased following dose reduction. Identifying patients who may benefit from a reduction in pasireotide dose warrants further research as it may improve the management of pasireotide-associated hyperglycaemia in susceptible patients.

Study of zeolite clinoptilolite d-glucose adsorption properties in vitro and in vivo

Beneficial effects of a natural zeolite clinoptilolite in vivo on mammals, including humans, have been empirically observed and documented in literature. The positive biological activities have been associated to its detoxifying and antioxidative properties, and its immunostimulative and adsorption properties. Herein, we present the in vitro and in vivo study of clinoptilolite zeolite materials adsorption properties for d-glucose. In particular, we present data on the interaction of d-glucose on the tested zeolites’ surface obtained by scanning electron microscope (SEM) and Energy-dispersive X-ray spectroscopy (EDS) and quantification by ultra high-performance liquid chromatography (UHPLC). We also present results on the reduction of blood glucose levels in mice pre-treated with clinoptilolite in vivo upon feeding with d-glucose. In vivo results were in line with the in vitro adsorption and/or interaction properties of tested zeolite materials for d-glucose and were quantified by UHPLC as well (11.34% for TMAZ; 10.82% for PMA and 8.76% for PMAO2). In vivo experiments in mice showed that PMA zeolite reduces blood glucose levels upon 15 min for 13% (at p < 0.05) up to 19.11% upon 120 min (without statistical significance) in clinoptilolite pre-treated mice fed by addition of d-glucose. Due to lack of explicit mechanistic knowledge on zeolite clinoptilolite interactions or adsorption with sugars in vitro and in vivo, presented study provides novel insights into these aspects for researchers in the field. The presented data merit further investigations as the material clearly shows a potential in management of hyperglycemia, such as for example in obese people, people with diabetes and people with metabolic syndrome where it could help regulate blood glucose levels.

Updates on the Management of Hyperglycemia in Hospitalized Adult Patients

Updates on the Management of Hyperglycemia in Hospitalized Adult Patients