Continuous Insulin Infusion Research Articles

Factors affecting time to recovery from diabetic ketoacidosis in adult diabetic patients in Alexandria Main University Hospital

BackgroundDiabetic ketoacidosis (DKA) is a life-threatening condition as a complication of diabetes and represents a significant healthcare global burden. The current study goal was to determine factors affecting time to recovery from DKA in Alexandria Main University Hospital.Patients and methodsOne hundred fifty patients who had been admitted with DKA were included in this study. All patients were managed with hospitalization for IV fluids, continuous intravenous insulin infusion, electrolyte correction, as well as detection and treatment of the predisposing factor until the full resolution of DKA.ResultsMales contributed to 58.7% of the total patients in this study with a mean age of 32.16 ± 15.06 years. DKA mean time of resolution was 18.76 ± 14.07 h. The majority of patients were with T1DM (86%), while T2DM were 14%. Missed insulin dose was the leading precipitating factor (60.7%) followed by infections (38.7%). There was a statistically significant relationship between DKA resolution time with age, time of presentation, type of diabetes, initial pH, initial serum K+ level, initial HCO3− level, initial anion gap, initial base excess, and initial RBS (p value < 0.001).ConclusionDelayed time of resolution from DKA was associated with initial lower pH, initial lower HCO3− level, initial lower base excess level, initial higher anion gap level, type 2 diabetes mellitus, patients on pre-mixed insulin regimen, old patients, delayed time for seeking medical care, and abnormal serum K+ level.

Glycemic Management in Patients with COVID-19 Admitted to the Intensive Care Unit: Evaluation of Glycemic Control and Drug Therapy.

Emerging evidence describes the high incidence and strong impact of hyperglycemia on the outcomes of critically ill patients with a diagnosis of COVID-19. Given resource limitations during the COVID-19 pandemic, clinicians moved away from using continuous IV infusions of insulin to manage hyperglycemia. To evaluate glycemic control in critically ill patients receiving various medication regimens to manage their hyperglycemia. This retrospective cohort study involved 120 mechanically ventilated adult patients (> 18 years) with COVID-19 who were admitted to the intensive care unit (ICU) between February 2020 and December 2021. The following data were collected for the first 14 days of the ICU admission: blood glucose values (up to 4 times daily), hypoglycemia events, and antihyperglycemic medication regimens. The use of IV insulin infusions maintained glucose measurements within the target range of 4 to 10 mmol/L more often than any other medication regimen, with 60% of measured values falling within the target range. The use of a sliding-scale insulin regimen maintained 52% of glucose measurements within the target range. Oral hypoglycemic agents performed relatively poorly, with only 12% to 29% of glucose measurements within range. The coadministration of corticosteroids led to worse glycemic control across all medication regimens. This study confirmed that ICUs should continue using the standard protocol of IV insulin infusion to achieve recommended blood glucose targets in critically ill patients with COVID-19, particularly those receiving corticosteroids.

6541 Recurrent Euglycemic Diabetic Ketoacidosis And Myonecrosis In A Patient Previously Thought To Have Type 2 Diabetes Mellitus

Abstract Disclosure: K. Haridas: None. M.M. McConnell : None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a well-recognized complication with the use of sodium linked cotransport of glucose-2 (SGLT2) inhibitors. Diabetic myonecrosis is a rare complication of diabetes mellitus caused by spontaneous death of muscle due to microvascular ischemia. Clinical Case: A 48-year-old male diagnosed with Type 2 Diabetes Mellitus with HbA1c 11.3%, treated with Empagliflozin and basal-bolus insulin was admitted to the hospital with left thigh pain and anorexia. Physical examination was notable for BMI of 19kg/m2 and left lateral thigh induration. Laboratory evaluation revealed venous pH 7.1, bicarbonate 10mmol/L (20-30), anion gap 32mmol/L(8-12), glucose 168mg/dl (65-99), ESR 67mm/h (&amp;lt;=12), Creatinine Kinase 31 U/L (63-473), glucosuria (4+) and ketonuria (4+). He was diagnosed with euglycemic DKA due to SGLT2 inhibitor. He was also diagnosed with Type 1 Diabetes Mellitus (T1DM) based on undetectable C-peptide and GAD antibody titer 64.3IU/ml(&amp;lt;5). MRI of the left thigh revealed an area of diabetic myonecrosis, measuring 11cm. He was treated with continuous insulin infusion. On hospital day 3, after resolution of the anion gap metabolic acidosis, transition was made to basal-bolus insulin. On hospital day 5, recurrent euglycemic DKA was diagnosed with bicarbonate 15mmol/L, anion gap 18mmol/L, beta-hydroxybutyrate 49.6mg/dl (&amp;lt;=3mg/dl), glucose 185mg/dl, glucosuria (4+) and ketonuria (4+). Continuous insulin infusion was restarted. On hospital day 8, transition was made to subcutaneous insulin. Diabetic myonecrosis was initially managed conservatively with analgesics, aspirin, and physical therapy. Due to worsening leukocytosis on hospital day 13, Ceftriaxone was started and surgical debridement was performed, revealing a loculated abscess within necrotic muscle. Empagliflozin was discontinued at discharge. Discussion: The risk of euglycemic DKA with SGLT2i use is increased in patients with T1DM and decreased oral intake, and insults like trauma or surgery as seen in this patient. Although the half-life of empagliflozin is 12 to 14 hours, there have been case reports of persistent or recurrent euglycemic DKA for 7-12 days from the time of last dose. The continued glucosuria and ketonuria in this patient with serum glucose levels below the renal threshold confirmed the recurrence. Diabetic myonecrosis usually affects the muscles of the proximal lower extremities and is seen in patients with poorly controlled diabetes with microvascular complications, between one and two decades after diagnosis, as in this patient. Conclusion: A high index of suspicion for recurrent euglycemic DKA must be maintained in patients who have new or persistent high anion gap metabolic acidosis until 2 weeks from last dose of SGLT2 inhibitor. Diabetic myonecrosis, especially if complicated by abscess formation, may require surgical intervention. Presentation: 6/1/2024

12618 A Rare Case Of Diabetic Ketoacidosis Leading To Severe Hypertriglyceridemia-induced Necrotizing Pancreatitis

Abstract Disclosure: E.R. Perez Roman: None. D.A. Lopez Rodriguez: None. K. Ramirez Gorbea: None. M. Sanchez Cordero: None. Y. Garcia Cruz: None. Acute pancreatitis is an acute inflammatory process of the pancreas that if left untreated can become complicated resulting in multiple organ damage and a fatal outcome in approximately 10%-40% of patients. There are well-known causes that can lead to pancreatitis such as alcohol, hereditary disorders, cholelithiasis, prior pancreatitis, and medications. Less frequently, it can be related to poorly controlled diabetes mellitus and diabetic ketoacidosis (DKA), given that in a state of low or deprived insulin, there is a breakdown of triglycerides into toxic fatty acids by pancreatic lipases; this lipotoxicity can result in the development of acute pancreatitis. We present a case of a 50-year-old woman with a past medical history of untreated hyperlipidemia and previous pancreatitis who was transferred to our institution with acute epigastric pain radiating to the back, nausea, and persistent vomiting. Upon arrival, blood glucose was 299 mg/dL, HbgA1c of 11.4%, lactic acid of 3.6 mmol/L, hypocalcemia of 6.0 mg/dl, hypoalbuminemia, and elevated pancreatic enzymes, amylase 869 U/L and lipase 2,493 U/L. The lipid panel was remarkable for total cholesterol of 1,085 mg/dL and triglycerides of 4,369mg/dL. Abdominopelvic CT scan confirmed acute pancreatitis with extensive peripancreatic and regional mesenteric edema. This patient was treated with aggressive IV fluid resuscitation and treated for DKA as per protocol. Despite prompt treatment, the patient rapidly deteriorated, developing pulmonary effusions and impending respiratory failure requiring mechanical ventilation. Her hyperglycemia was challenging to control and in the setting of severe hypertriglyceridemia, insulin requirements were higher, as intravenous insulin is useful in patients with concomitant findings, in the absence of plasmapheresis availability. Despite the marked reduction of triglyceride to 978 mg/dL and a decrease in pancreatic enzymes, multiorgan failure developed. Unfortunately, the patient died. Repeated abdominopelvic CT imaging revealed the progression of the disease to necrotizing pancreatitis involving the pancreatic head, uncinate process, and neck of the pancreas with evidence of a small hypodense lesion at the level of the tail of the pancreas. This case emphasizes the importance of prompt recognition of acute pancreatitis secondary to uncontrolled hyperglycemia with concomitant severe hypertriglyceridemia since it can lead to a worse clinical outcome as seen in our patient who developed rapid progression to necrotizing pancreatitis. It is paramount not to delay treatment with aggressive fluid resuscitation, continuous insulin infusion, and if available, plasmapheresis; as these treatment strategies in conjunction can be life-saving. Presentation: 6/3/2024

6844 Comparison of Lactated Ringers and Normal Saline in the Treatment of Diabetic Ketoacidosis

Abstract Disclosure: J.N. Johnson: None. A.T. Drincic: None. K. Nein: None. E. Buddenhagen: None. K. Samson: None. T. Langenhan: None. Background: Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. We hypothesized that the use of LR compared to NS for volume management in DKA will shorten time to DKA resolution, reduce time to DKA associated protocol insulin infusion discontinuation, and result in lower post-intravenous fluid resuscitation chloride values. Methods: We conducted a single institution, retrospective cohort study of patients admitted with the diagnosis of DKA following our institution’s transition from NS to lactated ringers (LR) as the default resuscitative and maintenance fluid in our DKA management protocol. Adult patients admitted with DKA before and after the protocol change were identified. The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol continuous insulin infusion. Results: Of 246 patients meeting inclusion criteria, 119 were stratified to the NS group (pre-protocol change) and 127 to the LR group (post-protocol change). T-test analysis revealed decreased time to DKA resolution in the LR group (mean 17.1 hours; SD 11.02) relative to the NS group (mean 20.6 hours; SD 12.22; p = .02). Duration of DKA protocol continuous intravenous insulin was shorter in the LR group (mean 16.0 hours; SD 8.72) compared to the NS group (mean 21.4 hours; SD 12.50; p = 0.0001). Conclusions: In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol continuous insulin infusion. Presentation: 6/2/2024

The Effects of Subcutaneous Rapid-Acting Insulin Aspart in the Treatment of Mild and Moderate Diabetic Ketoacidosis in Children: A Prospective Study.

Background and objectives The traditional treatment approach to diabetic ketoacidosis (DKA) involves the replacement of fluid and electrolyte deficits and a continuous intravenous infusion of regular insulin. Several clinical trials supported the administration of subcutaneous rapid-acting insulin analogs in the management of uncomplicated DKA. This study aimed to determine the effects/safety of subcutaneous rapid-acting insulin aspart injections in treating uncomplicated mild and moderate DKA in children. Methods In this prospective study in 2022, 25 children with mild/or moderate DKA were enrolled. The main outcome measure was median time (hours) for the resolution of ketoacidosis. Data recorded were as follows: clinical characteristics, severity of ketoacidosis and dehydration, blood glucose, sodium, potassium, creatinine, urine ketones, hospitalization's duration, and complications. Based on the degree of dehydration, fluid deficit was replaced by sodium chloride 0.45%. Insulin aspart 0.15 units/kg subcutaneous injections were given every 2 hours in the hospital outside ICU. Blood glucose was measured hourly and blood gases every 2 hours. Ketoacidosis was considered resolved when the patient did not have nausea/vomiting, was conscious, and could eat, and blood glucose was <250 mg/dL, pH was >7.30, and/or HCO3 was >15 mmol/L. Results Of 25 DKA patients (mean age 11.06±3.89, range 4-17 years, 60% girls), 16 cases (64%) had established type 1 diabetes. Overall, 13 (52%) cases had mild ketoacidosis (average pH=7.25), and 12 (48%) cases had moderate ketoacidosis (average pH=7.15). The mean time to resolution of ketoacidosis was 11.24 hours. All but one patient met DKA recovery criteria without complications. Mild cases compared to moderate cases of DKA had a shorter duration to resolution of DKA (p = 0.04). Mean duration of hospitalization was 2.3 days. No electrolyte disturbances, hypoglycemia events, readmission or mortality, or other adverse effects were observed. Conclusion In children with mild and moderate DKA, subcutaneous rapid-acting insulin aspart administration was an effective, safe, and convenient treatment.

Treatment of Severe Hyperglycemia in Extremely Preterm Infants Using Continuous Subcutaneous Insulin Therapy.

Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of iv insulin treatment. The aim of our study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Clinical data from 15 extemely premature infants (< 28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia at the NICU were included. Blood glucose levels during CSII as well as the nutritional intake and insulin intake were sampled. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Normoglycemia rates were best in the iv insulin-cohort (50.3%; 15.6%). Hypoglycemia was very rare in both groups (0.4%; 0.0%). CSII therapy might require higher insulin doses compared to continuous iv therapy. Subcutaneous Insulin therapy in extremely preterm infants is feasible, regarding the prevention of hypoglycemia. However, dose control needs to be improved. The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII.

Ketosis-prone Diabetes Presenting with Acute Esophageal Necrosis or “Black Esophagus”: An Intriguing New Clinical Association

Background:: Ketosis-prone diabetes (KPD) is an intermediate subtype of diabetes mellitus, usually affecting Afro-American adults, presenting with diabetic ketoacidosis (DKA), without the classic phenotype of autoimmune type 1 diabetes. Patients require insulin therapy at onset for the acute decompensation, then usually remain insulin-free for prolonged periods with diet alone or with other antidiabetic drugs. DKA can be rarely complicated by upper gastrointestinal bleeding and mucosal necrosis, a severe complication named acute esophageal necrosis (AEN) burdened by high mortality. The association of KPD presenting with DKA complicated by AEN is here reported for the first time, to the knowledge of the authors, in the medical literature. Case Presentation:: Here we report an interesting case of middle-aged African woman, newly diagnosed with KPD, presenting with DKA hematemesis. The patient was first treated at Intensive Care Unit for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. At the same time, esophagogastroduodenoscopy (EGD) was performed to diagnose acute esophageal necrosis, which was promptly managed with proton pump inhibitors infusion, fasting, and parenteral nutrition. After the correct clinical evaluation, the patient was switched to oral antidiabetic and basal insulin at discharge and an EGD follow-up was scheduled. Conclusions:: KPD remains an under-recognized and under-diagnosed type of diabetes which can present as DKA. Since DKA could be a possible trigger of AEN, a rare but potentially lifethreatening condition, that clinicians should be aware of, in patients presenting with upper gastrointestinal bleeding and ketoacidosis. The prompt management and classification of DKA, combined with the EGD execution for early AEN diagnosis and follow-up, is essential.

Unraveling a Novel Mechanism of Altered Glomerular Hemodynamics in Pre-diabetic Obesity

Background: In pre-diabetic obesity, disrupted glomerular autoregulation leads to increased glomerular capillary pressure and renal blood flow, causing potential barotrauma-induced glomerular damage. A decrease in Afferent arteriole ( Af-Art) resistance causes higher glomerular capillary pressure but the underlying mechanism behind this, specifically in pre-diabetic obesity, remains unclear. Hyperinsulinemia is common in pre-diabetic obesity, but its role in reducing Af-Art resistance in the kidneys is unknown. Kidney blood flow is auto-regulated by vasoconstriction via tubuloglomerular feedback (TGF) and vasodilation through the Distal convoluted tubule-2/connecting tubule (DCT-2/CNT) mechanism. Our earlier studies indicate increased Af-Art dilation in pre-diabetic obese rats through the DCT-2/CNT mechanism without affecting TGF. This DCT-2/CNT induced Af-Art dilation requires initiation from epithelial sodium channels (ENaC) present at this tubular segment and interestingly insulin is a known ENaC activator. Hypothesis: We hypothesize that in the context of pre-diabetic obesity, hyperinsulinemia contributes to an increase in renal cortical blood flow (CBF) by increasing DCT-2/CNT-induced Af-Art dilation, subsequently leading to glomerular injury. Methods: We assessed the effects of insulin on Af-Art dilation by perfusing juxtaposed DCT-2/CNT segments with insulin in normal rabbits. Contribution of DCT-2/CNT induced Af-Art dilation was measured by co-administration of the ENaC blocker benzamil. To study hyperinsulinemia's role in an in-vivo setting without altering blood glucose levels, we used a hyperinsulinemic-euglycemic (HI-EUG) clamp in obese rats with intravenous (IV) glucose and insulin infusions. Renal CBF and blood pressure were monitored using a laser Doppler probe and femoral artery catheter, respectively, both with and without benzamil administration (400 μg/kg, IV). To evaluate insulin's potential role in causation of renal damage, we infused insulin directly into one kidney of lean rats for 6 weeks via a renal sub-capsular catheter, with the contralateral kidney serving as control. Glomerular basement membrane (GBM) thickness, a marker of renal damage, was measured via electron microscopy. Untargeted lipidomic analysis of the renal cortex was performed to identify potential renal damage pathways in insulin infused kidneys. Results: Insulin perfusion in rabbits' DCT-2/CNT potentiated the dilation of adherent Af-Art compared to control infusions with artificial tubular fluid. ENaC inhibition reversed the insulin-induced Af-Art dilation, confirming that insulin increases Af-Art dilation through the ENaC-initiated DCT-2/CNT mechanism. In obese rats, insulin delivery using a HI-EUG clamp resulted in a significant 20.8±4.9% increase in CBF, which was negated by the administration of the ENaC blocker benzamil, indicating the potential involvement of DCT-2/CNT-mediated vasodilation. Neither the HI-EUG clamp nor benzamil infusion affected blood pressure. Additionally, continuous direct insulin infusion into the kidneys of lean rats led to an increase in glomerular basement membrane (GBM) thickness and ceramide accumulation in the renal cortex, both indicative of renal damage. Conclusion: Our study demonstrates that insulin directly augments DCT-2/CNT-mediated Af-Art dilation and increases renal cortical blood flow in obese rats. Chronic renal insulin infusion led to structural changes and damage markers in the kidney, independent of blood glucose and blood pressure levels. Henry Ford Health System Internal Funding. Pilot and Feasibility grant from southeast center for integrated metabolomics. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Signs and symptoms in the diagnosis of type 1 diabetes mellitus and interventions for the management of diabetic ketoacidosis: scoping review

Objective: To identify the most prevalent signs and symptoms in the diagnosis of Type 1 Diabetes Mellitus (DM1) in children and adolescents, as well as the signs and symptoms of Diabetic Ketoacidosis (DKA), its complications, and the nursing and medical interventions indicated for its management. Method: This is a scoping review, carried out in the LILACS, PUBMED, SCOPUS, LIVIVO, and Embase databases, with additional search in gray literature. The data were analyzed qualitatively. Results: We found 840 studies in the search, but only 10 studies met the eligibility criteria. The most frequent signs and symptoms in the diagnosis of DM1 were polydipsia (83%), polyuria (78%), and weight loss (56%). DKA symptoms were variable. The main complications of DKA were cerebral edema and death and transfer to the pediatric intensive care unit and continuous infusion of intravenous insulin were the most recommended interventions. Conclusion: Early recognition of the signs and symptoms of DM1 plays an important role in patient management, leading to rapid initiation of treatment and relevant interventions, thus preventing the occurrence of complications.

Feasibility and Performance of Continuous Glucose Monitoring to Guide Computerized Insulin Infusion Therapy in Cardiovascular Intensive Care Unit.

We evaluated the feasibility of real-time continuous glucose monitoring (CGM) for titrating continuous intravenous insulin infusion (CII) to manage hyperglycemia in postoperative individuals in the cardiovascular intensive care unit and assessed their accuracy, nursing acceptance, and postoperative individual satisfaction. Dexcom G6 CGM devices were applied to 59 postsurgical patients with hyperglycemia receiving CII. A hybrid approach combining CGM with periodic point-of-care blood glucose (POC-BG) tests with two phases (initial-ongoing) of validation was used to determine CGM accuracy. Mean and median absolute relative differences and Clarke Error Grid were plotted to evaluate the CGM accuracy. Surveys of nurses and patients on the use of CGMs experience were conducted and results were analyzed. In this cohort (mean age 64, 32% female, 32% with diabetes) with 864 paired POC-BG and CGM values analyzed, mean and median absolute relative difference between POC-BG and CGM values were 13.2% and 9.8%, respectively. 99.7% of paired CGM and POC-BG were in Zones A and B of the Clarke Error Grid. Responses from nurses reported CGMs being very or quite convenient (n = 28; 93%) and it was favored over POC-BG testing (n = 28; 93%). Majority of patients (n = 42; 93%) reported their care process using CGM as being good or very good. This pilot study demonstrates the feasibility, accuracy, and nursing convenience of adopting CGM via a hybrid approach for insulin titration in postoperative settings. These findings provide robust rationale for larger confirmatory studies to evaluate the benefit of CGM in postoperative care to improve workflow, enhance health outcomes, and cost-effectiveness.

Multiple daily injection insulin regimen is an effective, and more economical, alternative to continuous insulin infusion for type 1 diabetics

A clinical decision report using: Heller S, White D, Lee E, et al. A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial. Health Technol Assess. 2017 Apr;21(20):1-278. https://doi.org/10.3310/hta21200 for a patient with type 1 diabetes.

Insulin Infusion Protocols for Blood Glucose Management in Critically Ill Patients: A Scoping Review.

Continuous insulin infusion is a method for maintaining blood glucose stability in critically ill patients with hyperglycemia. Many insulin infusion protocols have been applied in intensive care units. Understanding the content of these protocols can help clinical staff choose the most appropriate and convenient protocol and promote best practices in managing glucose levels in critically ill adult patients. To examine the types of insulin infusion therapies performed for blood glucose management in critically ill patients. For this scoping review, 3 Chinese-language and 8 English-language databases were searched for articles published from May 25, 2016, to October 25, 2022. Twenty-one articles met the inclusion criteria. Twenty-one insulin infusion protocols were examined. Most of the insulin infusion protocols were paper protocols. Fourteen glucose management indicators were included in the 21 protocols. The glucose target range for all 21 protocols ranged from 70 to 180 mg/dL (3.9-10.0 mmol/L). Nurses were primarily responsible for protocol implementation in most protocol development processes. The roles of nurses differed in nurse-led insulin infusion protocols and non-nurse-led insulin infusion protocols. This scoping review indicates an urgent need for more comprehensive glycemic control guidelines for patients receiving critical care. Because insulin infusion protocols are core aspects of blood glucose management guidelines, different population subgroups should also be considered. Nurse-led guidelines must be based on the best available evidence and should include other variables related to glucose management (eg, patient disease type, medication, and nutrition) in addition to insulin infusion.

Case of hypertriglyceridemia-induced subacute pancreatitis and hypertriglyceridemia-triggered transverse sinus thrombosis in a recently diagnosed diabetic patient and the efficacy of management of hypertriglyceridemia with continuous insulin infusion

ABSTRACT A 28-year-old single female diagnosed with transverse sinus thrombosis; she was also discovered to be diabetic with severe hyperlipidemia. She presented by recurrent episodes of diffuse dull aching abdominal pain referred to the back; she was diagnosed with acute pancreatitis with markedly elevated triglyceride (TG) levels. She started medical treatment for hypertriglyceridemia with no improvement. She started four sessions of plasma exchanges with marked improvement of the general condition, abdominal pain and appetite, and TGs declined.While the patient was on plasma exchange she developed catheter related infection so it is stopped and soon triglycerides raised again with recurrence of the abdominal pain and we started insulin infusion with improvement of her condition

A novel class of oral, non-immunosuppressive, beta cell-targeting, TXNIP-inhibiting T1D drugs is emerging.

Diabetes treatment options have improved dramatically over the last 100 years, however, close to 2 million individuals in the U.S. alone live with type 1 diabetes (T1D) and are still dependent on multiple daily insulin injections and/or continuous insulin infusion with a pump to stay alive and no oral medications are available. After decades of focusing on immunosuppressive/immunomodulatory approaches for T1D, it has now become apparent that at least after disease onset, this by itself may not be sufficient, and in order to be effective, therapies need to also address beta cell health. This Perspective article discusses the emergence of such a beta cell-targeting, novel class of oral T1D drugs targeting thioredoxin-interacting protein (TXNIP) and some very recent advances in this field that start to address this unmet medical need. It thereby focuses on repurposing of the antihypertensive drug, verapamil found to non-specifically inhibit TXNIP and on TIX100, a new chemical entity specifically developed as an oral anti-diabetic drug to inhibit TXNIP. Both have shown striking anti-diabetic effects in preclinical studies. Verapamil has also proven to be beneficial in adults and children with recent onset T1D, while TIX100 has just been cleared by the U.S. Food and Drug Administration (FDA) to proceed to clinical trials. Taken together, we propose that such non-immunosuppressive, adjunctive therapies to insulin, alone or in combination with immune modulatory approaches, are critical in order to achieve effective and durable disease-modifying treatments for T1D.

Management of diabetic ketoacidosis in internal medicine: insulin protocols, electrolyte balance, and clinical outcomes

Diabetic ketoacidosis (DKA) is a critical complication of diabetes mellitus (DM), characterized by hyper-glycemia, acidosis, and ketosis. It poses a substantial risk of morbidity and mortality, especially in type 1 DM patients. DKA can be triggered by various factors, including insulin deficiency, infections, alcohol abuse, and other medical conditions. Hospital admissions for DKA are increasing, with mortality rates of up to 5-9%, often linked to severe underlying illnesses and complications such as myocardial infarction and stroke. Effective DKA management involves rehydration, correction of electrolyte imbalances, insulin administration, and addressing precipitating factors. Fluid resuscitation with isotonic saline is vital to restore hydration, and continuous intravenous insulin infusion is the preferred method to control blood glucose and suppress ketone production. Electrolyte imbalances, particularly potassium, sodium, phosphate, and magnesium, require careful monitoring and correction. Clinical outcomes in DKA management include resolving acidosis, normalizing blood glucose, and restoring electrolyte balance, all while achieving and maintaining clinical stability. Complications like cerebral edema and acute respiratory distress syndrome can significantly impact the prognosis. Long-term considerations encompass diabetes management, patient education, and follow-up care.

A Nutritional Approach to Optimizing Pump Therapy in Type 1 Diabetes Mellitus

Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient–practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.

SAT364 A Rare Cause of Hyperandrogenism in a Premenopausal Woman

Abstract Disclosure: L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. A. Rosado-Burgos: None. M.A. Ortiz-Rivera: None. B. Torres Rivera: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. M. Marcos Martínez: None. M. Correa Rivas: None. N. Bracero, MD: None. Hyperandrogenism in premenopausal women is most commonly associated to polycystic ovarian syndrome (PCOS). Approximately 10% of females in reproductive age present with clinical and/or biochemical findings of androgen excess, such as hirsutism, acne, alopecia, oligo-amenorrhea or if hyperandrogenism is severe it can lead to extreme virilization. Androgen excess can also contribute to insulin resistance. In this case we discuss a patient with severe hyperandrogenism, extreme insulin resistance and a rare cause of androgen excess in a woman of childbearing age. 34-year-old female patient G0P0 with type 2 diabetes mellitus (T2DM) on continuous insulin infusion system (CIIS), familial partial lipodystrophy, PCOS and severe hyperandrogenism, who was referred to our clinics for management of uncontrolled T2DM. Patient was on CIIS with regular insulin U-500 using a total daily dose of 95 units. She referred amenorrhea for the past 12 years and significant progression of hirsutism, alopecia and acanthosis nigricans in the past two years. Patient had clinical findings of hyperandrogenism such as hirsutism evaluated with modified Ferriman-Gallwey scale with a score of 32, alopecia Ludwig class 3 and marked acanthosis nigricans in neck and abdomen.Pre-operative laboratories: hemoglobin (Hgb) level 15.13 g/dL, hematocrit (Ht) 44.59 %, total testosterone level 525 ng/dL (13-53 ng/dL) and DHEAS 113 ug/dL (95.8-511.7 ug/dL), suggesting an ovarian source of androgen excess. Transvaginal ovarian ultrasound showed at the posteromedial edge of right ovary a hyperechoic structure measuring 1.5 cm long x 1.0 cm AP representing a lesion of unknown etiology. After discussion with patient a decision for oophorectomy was made. Pathology report described the ovary negative for neoplasia with findings consistent with hyperthecosis. Laboratories two weeks post-operative showed significant decrease in total testosterone to 81 ng/dL and in Hgb/ Ht (12.50 g/dL and 37.8% respectively). Insulin requirement decreased and she was able to be transitioned to U-100 insulin lispro with a total daily dose of 100. Four weeks after surgery patient had her menstrual period. Ovarian hyperthecosis is a disorder where there is an increased tissue with luteinized theca cells in the ovarian stroma; these cells are ovarian interstitial cells that differentiate into steroidogenically active cells. It is most commonly observed in post-menopausal women, but it has been described in women of childbearing age presenting with worsening hirsutism, virilization and insulin resistance. Monitoring patterns and progression of androgen excess is important in premenopausal women with a diagnosis of PCOS. Severe biochemical or clinical presentation, as well as progression of hyperandrogenism should increase suspicion of additional pathological entities as it will improve patient’s quality of life with the appropriate management. Presentation Date: Saturday, June 17, 2023

Continuous insulin infusion versus sliding scale for perioperative glycemic control in diabetic patients undergoing elective hip arthroplasty

Continuous insulin infusion versus sliding scale for perioperative glycemic control in diabetic patients undergoing elective hip arthroplasty

Hyperglycemia and insulin infusion in pancreatoduodenectomy: a prospective cohort study on feasibility and impact on complications.

Hyperglycemia is a risk factor for postoperative complications but its impact on outcome after pancreatoduodenectomy (PD) is scarcely studied. This prospective cohort study aimed to assess the effect of continuous insulin infusion on postoperative complications and blood glucose, as well as to evaluate the impact of hyperglycemia on complications, after PD. One hundred patients planned for PD at Skåne University Hospital, Sweden were prospectively included for perioperative continuous insulin infusion and a historic cohort of 100 patients was included retrospectively. Median blood glucose levels were calculated and data on complications were analyzed and compared between the historic cohort and the intervention group as well as between normo- and hyperglycemic patients. Median glucose levels were significantly lower in the intervention group compared to the historic cohort up to 30 days postoperatively (median glucose 8.5mmol/l (interquartile range 6.4-11) vs. 9.1mmol/l (interquartile range 6.8-17) ( P =0.007)). No significant differences in complication rates were recorded between these two groups. The incidence of complications classified as Clavien ≥3 was higher in hyperglycemic patients (100 vs. 27%, P =0.024). Among hyperglycemic patients the prevalence of preoperative diabetes was higher compared to normoglycemic patients (52 vs.12%, P <0.001). In patients with a known diagnosis of diabetes, a trend, although not statistically significant, towards a lower incidence of postoperative pancreatic fistula grade B and C, as well as postpancreatectomy hemorrhage grade B and C, was seen compared to those without preoperative diabetes (6.8 vs. 14%, P =0.231 and 2.3 vs. 7.0%, P =0.238, respectively). Insulin infusion in the early postoperative phase after PD is feasible in a non-ICU setting and significantly decreased blood glucose levels. The influence on complications was limited. Preoperative diabetes was a significant predictor of postoperative hyperglycemia and was associated with a lower incidence of clinically significant postoperative pancreatic fistula.