Continuous Insulin Research Articles

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.

Low-Dose Antithymocyte Globulin: A Pragmatic Approach to Treating Stage 2 Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) (2.5 mg/kg) preserves C-peptide and reduces HbA1c in new-onset stage 3 type 1 diabetes, yet efficacy in delaying progression from stage 2 to stage 3 has not been evaluated. Children (n = 6) aged 5-14 years with stage 2 type 1 diabetes received off-label, low-dose ATG. HbA1c, C-peptide, continuous glucose monitoring, insulin requirements, and side effects were followed for 18-48 months. Three subjects (50%) remained diabetes free after 1.5, 3, and 4 years of follow-up, while three developed stage 3 within 1-2 months after therapy. Eighteen months posttreatment, even disease progressors demonstrated near-normal HbA1c (5.1% [32 mmol/mol], 5.6% [38 mmol/mol], and 5.3% [34 mmol/mol]), time in range (93%, 88%, and 98%), low insulin requirements (0.17, 0.18, and 0.34 units/kg/day), and robust C-peptide 90 min after mixed meal (1.3 ng/dL, 2.3 ng/dL, and 1.4 ng/dL). These observations support additional prospective studies evaluating ATG in stage 2 type 1 diabetes.

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.

Ultrarapid Insulin Use Can Reduce Postprandial Hyperglycemia and Late Hypoglycemia, Even in Delayed Insulin Injections: A Connected Insulin Cap-Based Real-World Study.

Objectives: Reaching optimal postprandial glucose dynamics is a daily challenge for people with type 1 diabetes (T1D). This study aimed to analyze the postprandial hyperglycemic excursion (PHEs) and late postprandial hypoglycemia (LPH) risk according to prandial insulin time and type. Research Design and Methods: Real-world, retrospective study in T1D using multiple daily injections (MDI) analyzing 5 h of paired continuous glucose monitoring and insulin injections data collected from the connected cap Insulclock®. Meal events were identified using the rate of change detection methodology. Postprandial glucometrics and LPH (glucose <70 mg/dL 2-5 h after a meal) were evaluated according to insulin injection time and rapid (RI) or ultrarapid analog, Fiasp® (URI), use. Results: Meal glycemic excursions (n = 2488), RI: 1211, 48.7%; UR: 1277, 51.3%, in 82 people were analyzed according to injection time around the PHE: -45 to -15 min; -15 to 0 min; and 0 to +45 min. In 63% of the meals, insulin was injected after the PHE started. Lower PHE was observed with URI versus RI (glucose peak-baseline; mg/dL; mean ± standard deviation): 106.7 ± 35.2 versus 111.2 ± 40.3 (P = 0.003), particularly in 0/+45 injections: 111.6 ± 40.2 versus 118.1 ± 43.3; (P = 0.002). One third (29.1%) of participants added a second (correction) injection. The use of URI and avoiding a second injection were independently associated with less LPH risk, even in delayed injections (0/+45), (-36%, odds ratio [OR] 0.641; confidence interval [CI]: 0.462-0.909; P = 0.012) and -56% (OR 0.641; CI: 0.462-0.909 P = 0.038), respectively. Conclusions: URI analog use as prandial insulin reduces postprandial hyper- and hypoglycemia, even in delayed injections.

Encapsulated stem cell–derived β cells exert glucose control in patients with type 1 diabetes

Clinical studies on the treatment of type 1 diabetes with device-encapsulated pancreatic precursor cells derived from human embryonic stem cells found that insulin output was insufficient for clinical benefit. We are conducting a phase 1/2, open-label, multicenter trial aimed at optimizing cell engraftment (ClinicalTrials.gov identifier: NCT03163511). Here we report interim, 1-year outcomes in one study group that received 2–3-fold higher cell doses in devices with an optimized membrane perforation pattern. β cell function was measured by meal-stimulated plasma C-peptide levels at 3-month intervals, and the effect on glucose control was assessed by continuous glucose monitoring (CGM) and insulin dosing. Of 10 patients with undetectable baseline C-peptide, three achieved levels ≥0.1 nmol l−1 from month 6 onwards that correlated with improved CGM measures and reduced insulin dosing, indicating a glucose-controlling effect. The patient with the highest C-peptide (0.23 nmol l−1) increased CGM time-in-range from 55% to 85% at month 12; β cell mass in sentinel devices in this patient at month 6 was 4% of the initial cell mass, indicating directions for improving efficacy.

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.

Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial

Aims/hypothesisHypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown.MethodsUsing a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18–40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up.ResultsWe recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg−1 min−1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms.Conclusions/interpretationDespite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels.Trial registrationEudraCT number 2021-001243-27.FundingThis study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014).Graphical

Benchmarking Diabetes Technology Use Among 21 U.S. Pediatric Diabetes Centers.

The American Diabetes Association's Standards of Care in Diabetes recommends the use of diabetes technology such as continuous glucose monitoring systems and insulin pumps for people living with type 1 diabetes. Unfortunately, there are multiple barriers to uptake of these devices, including local diabetes center practices. This study aimed to examine overall change and center-to-center variation in uptake of diabetes technology across 21 pediatric centers in the T1D Exchange Quality Improvement Collaborative. It found an overall increase in diabetes technology use for most centers from 2021 to 2022 with significant variation.

RESULTS OF GLYCEMIC CONTROL AMONG SEVERE STROKE PATIENTS

Background: Hyperglycemia is a relatively common condition in stroke patients, whether they have diabetes or not, and it is associated with adverse outcomes. Achieving target blood glucose levels has a partial impact on the results, but it is not the sole determinant. Objectives: We assessed the result of glycemic control among severe stroke patients. Materials and methods: A prospective study was conducted in the Stroke Department, Can Tho Central General Hospital, from June 2020 to April 2022, with 72 severe stroke patients monitored the capillary blood glucose every 3 hours. Nineteen patients who had persistent hyperglycemia were controlled with continuous intravenous insulin. We determined the average blood glucose level for each patient, the time needed to reach the glycemic target range, the frequency of hypoglycemia, and the glycemic variability from all measured blood glucose concentration. R programming was used to analyze the data. Results: The average age of patients was 65.1±16.1. The percentage of ischemic stroke, accounting for 55.6%, was the highest, followed by cerebral hemorrhage at 34.7%, 1.4% of these patients was attributed to cerebral venous thrombosis. In admission, the median Glasgow score was 8 (IQR: 7-9), and the median modified Rankin score was 5 (IQR: 4-5). Enteral nutrition was the primary nutritional therapy. Among 53 severe strokes without persistent hyperglycemia, blood glucose levels fluctuated around the mean value of 143 mg/dL. In 19 patients with persistently elevated blood glucose concentration, the mean blood glucose levels preinfusion and post-insulin infusion were 299±117mg/dL and 165±43.2mg/dL, respectively; time to glycemic target was 8.25 hours (95% CI: 3.50-14.75 hours), the minimum was 3 hours, and the longest was 189 hours; 5.3% of these patients developed hypoglycemia, and 13.3% of persistent hyperglycemia patients did not obtain the target range. Conclusions: Blood glucose levels fluctuate within the target range among patients with nonhyperglycemia or non-persistent hyperglycemia. In patients with persistent hyperglycemia controlled with intravenous insulin, the mean blood glucose levels were achieved close to the upper limit of the glycemic target.

Utility and precision evidence of technology in the treatment of type 1 diabetes: a systematic review

BackgroundThe greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care.MethodsScreening of 835 peer-reviewed articles was followed by systematic review of 70 of them (focusing on randomized trials and extension studies with ≥50 participants from the past 10 years).ResultsWe find that novel technologies, ranging from continuous glucose monitoring systems, insulin pumps and decision support tools to the most advanced hybrid closed loop systems, improve important measures like HbA1c, time in range, and glycemic variability, while reducing hypoglycemia risk. Several studies included person-reported outcomes, allowing assessment of the burden or benefit of the technology in the lives of those with type 1 diabetes, demonstrating positive results or, at a minimum, no increase in self-care burden compared with standard care. Important limitations of the trials to date are their small size, the scarcity of pre-planned or powered analyses in sub-populations such as children, racial/ethnic minorities, people with advanced complications, and variations in baseline glycemic levels. In addition, confounders including education with device initiation, concomitant behavioral modifications, and frequent contact with the healthcare team are rarely described in enough detail to assess their impact.ConclusionsOur review highlights the potential of technology in the treatment of people living with type 1 diabetes and provides suggestions for optimization of outcomes and areas of further study for precision medicine-directed technology use in type 1 diabetes.

THU530 What Works For Ferret, Works For Man

Abstract Disclosure: P.J. Bhatt: None. S. Bendaram: None. V. Kantorovich: None. Insulinomas are rare pancreatic neuroendocrine tumors with an incidence of 4 cases per million per year and present with hypoglycemic symptoms due to uncontrolled and excessive insulin secretion by the tumor. Although most commonly benign and treated with surgery, 5-10% are malignant, inoperable and are managed medically with somatostatin analogs, chemotherapy, mTOR inhibitors and diazoxide. A 28 year old male with a history of metastatic insulinoma with progressive disease and refractory hypoglycemia presented with lethargy, diaphoresis, and blood glucose (BG) level of 32mg/dL [65-99]. He was previously admitted for severe hypoglycemia and was treated with FOLFOX, LUTATHERA, Octreotide, TPN, steroids and diazoxide suspension. Sugars were monitored via continuous glucose monitor (CGM) and insulin and C-peptide levels were closely monitored outpatient. Treatment was effective and medications were tapered off so that he no longer needed a CGM and was only on FOLFOX and octreotide prior to presentation. On admission, insulin level was 172 uIU/mL [&amp;lt;17], peaking at 312 uIU/mL and BG dropping to 22mg/dL. He was placed on a dextrose 10% infusion, TPN, diazoxide suspension, and CGM. This admission, however, his insulin levels were much higher requiring higher doses of diazoxide, but he was unable to tolerate the diazoxide solution due to extreme nausea and projectile vomiting, resigning him to a long-term stay in the ICU. Due to a lack of availability of other oral formulations in the US, compounding pharmacies were contacted and pharmaceutical grade diazoxide powder was compounded into 100mg capsules by an outside pharmacy. Dose was adjusted while monitoring BG and insulin levels. Prior to discharge, insulin level was 77.7 uIU/mL and BG levels had normalized. He was sent home on diazoxide 200mg twice a day, TPN, and CGM. FOLFOX was resumed. Outpatient follow up revealed euglycemia and suppressed insulin level of 12.3 uIU/mL [&amp;lt;17], allowing for further tapering of diazoxide dose and discontinuation of TPN. Diazoxide is known to be a safe and effective treatment for hypoglycemia in humans and ferrets alike. It inhibits insulin secretion in pancreatic B cells and increases hepatic glucose production. Side effects of nausea and vomiting can be a barrier to compliance, as seen in our patient. Currently, only oral solutions of diazoxide have been approved for human consumption whereas ferrets, commonly afflicted with insulinomas, are treated with oral pills. Changing the oral formulation to pill form allowed for better compliance, easy dose adjustments using insulin as a marker for response, and symptom resolution due to adequate suppression of insulin levels. Most importantly, it allowed for our patient to transfer out of the ICU and be discharged home with improved quality of life, a feat that was impossible without this change in formulation. Presentation: Thursday, June 15, 2023

THU006 Exploring Primary Care Resident Perspectives On Diabetes Education In Training

Abstract Disclosure: N. Francis: None. S. Cardillo: None. D.R. Nandiwada: None. Background: The training residents gain in Family Medicine (FM) and Internal Medicine (IM) residency programs provide a critical foundation for their knowledge in diabetes (DM) management. It is one of the most common diagnoses physicians-in-training will encounter in their residency training programs and in clinical settings. However, a 2012 study compared diabetes care in resident clinics versus private physicians and found significant decrease in patient satisfaction (56.5% vs. 71.3%) in resident clinics. A 2020 study surveying primary care (PC) residency program directors showed that most FM and IM residency training programs focus on the core diabetes care and management topics with much less focus on emerging topics, such as 2nd generation insulin analogs and digital health technologies. The purpose of our survey was to better assess current resident perceptions and attitudes towards their DM education and their perceived comfort level in comprehensive DM counseling, evaluation, and management. Methods: A 12 item survey was designed using the Qualtrics program. The survey link was sent via email to IM- PC and FM residents at a major academic medical center. Data was collected from September 13th, 2022 to present. The survey included a combination of multiple choice, Likert scale and ranking questions. Results: 14 residents responded to the survey to date with the majority (71%) belonging to the IM-PC group and the remainder (29%) family medicine. Residents felt most comfortable managing diabetes related complications and counseling on foot and eye care and hypoglycemia. Respondents reported being most uncomfortable in prescribing non-insulin medication (50%) and initiating an insulin regimen (43%) and less comfortable counseling patients on continuous glucose monitoring systems (83%) and insulin administration (66%). While majority of residents (72%) found their DM curriculum clinically relevant, 85% of residents reported there was not enough time allotted. Respondents felt a more longitudinal lecture series, with increased access to treatment frameworks and on-site feedback on their DM counseling and care would best supplement their DM curriculum. Conclusion: This survey data explores specific areas that residents have identified as being least comfortable and also expresses what they identified as the most preferable ways to modify and design an educational intervention. This information allows for tailored curricular intervention highlighting diabetes technologies, insulin and non-insulin prescribing practice in a longitudinal lecture style format that provides access to DM treatment frameworks and incorporates direct on-site feedback to the residents. This provides evidence for the development of a novel clinically integrated DM curriculum. Presentation: Thursday, June 15, 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&amp;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

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

2023 Clinical Practice Guidelines for Diabetes: Continuous Glucose Monitoring and Insulin Pumps

With the expanding use of continuous glucose monitoring (CGM) and insulin pumps worldwide, several international guidelines dedicated to diabetes technology have been developed. Recently, the Korean Diabetes Association released a new version of their clinical practice guidelines including substantial changes in recommendations on the use of CGM and insulin pumps. Of note, continuous use of real-time CGM is now recommended to all people with diabetes using insulin, including people with type 2 diabetes using once daily basal insulin. Convincing evidence from recent automated insulin delivery (AID) trials supports the recommendation of AID as standard therapy in type 1 diabetes. This review summarizes the results of recent clinical studies on CGM and AID and their influence on the new clinical recommendations.

Longitudinal Trends in Glycemic Outcomes and Technology Use for Over 48,000 People with Type 1 Diabetes (2016-2022) from the T1D Exchange Quality Improvement Collaborative.

Previous studies revealed that HbA1c increased overall in the U.S. in the past decade. Additionally, health inequities in type 1 diabetes (T1D) outcomes by race-ethnicity and insurance type persist. This study examines the trends in HbA1c from 2016 to 2022 stratified by race-ethnicity and insurance in a large multicenter national database. We analyzed glycemic outcomes and diabetes device use trends for over 48,000 people living with type 1 diabetes (PwT1D) from three adult and twelve pediatric centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI), comparing data from 2016-2017 with data from 2021-2022. The mean HbA1c in 2021-2022 was lower at 8.4% compared to the mean HbA1c in 2016-2017 of 8.7% (0.3% improvement; p<0.01). Over the same period, the percentage of PwT1D using a continuous glucose monitor (CGM), insulin pump, or hybrid closed-loop system increased (45%, 12%, and 33%, respectively). However, these improvements were not equitably demonstrated across racial-ethnic groups or insurance types. Racial-ethnic and insurance-based inequities persisted over all seven years across all outcomes; comparing non-Hispanic White and non-Hispanic Black PwT1D, disparate gaps in HbA1c (1.2-1.6%), CGM (30%), pump (25-35%), and HCLS (up to 20%) are illuminated. Population-level data on outcomes, including hemoglobin A1c (HbA1c), can provide trends and insights into strategies to improve health for PwT1D. The T1DX-QI cohort showed a significant improvement in HbA1c from 2016-2022. Improvements in diabetes device use are also demonstrated. However, these increases were inconsistent across all racial-ethnic groups or insurance types, an important focus for future T1D population health improvement work.

Effects of Type 1 Diabetes Mellitus on Linear Growth: A Comprehensive Review.

Type 1 diabetes mellitus (T1DM) has a significant effect on the growth of children. The disease has a negative effect on growth when considered in relation to the time period and metabolic control. Studies in this review have suggested debilitated growth in children with T1DM and have a few anomalies in the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis when compared to fit children. Some studies show that children with T1DM were taller before the onset of the disease and during early diagnosis. Moreover, the linear growth depends on the interaction between the gonadotropin hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid hormones axis and GH-IGF-1; there's a rise in GH during puberty, which has an effect on the estrogen and testosterone, which leads to the pulsatile secretion of GH, this increment leads to insulin resistance. These studies suggest short stature in girls, and some suggest in both. The final height in boys was unchanged, but a slight decline was observed in girls. This review aims to provide the latest understanding of impaired heightin children with T1DM. The most accepted and effective treatment of impaired growth is the administration of long-acting insulin or continuous rapid-acting insulin. However, height was affected by the administration of good basal insulin at puberty and was unaffected by the continuous subcutaneous insulin injection. Hence, new technologies are the therapeutic regimen in children, especially the prepubertal age group; it will be interesting to see their effects on growth patterns in these children with T1DM.

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.

Demographic Variables Associated With Diabetes Technology Awareness or Use in Adults With Type 2 Diabetes.

Studies in populations with type 1 diabetes highlight racial/ethnic disparities in the use of diabetes technology; however, little is known about disparities among those with type 2 diabetes. This project investigates the racial/ethnic and socioeconomic disparities in diabetes technology awareness and use in adults with type 2 diabetes in the ambulatory setting. Adults ≥40 years of age with type 2 diabetes in ambulatory care were invited to participate via an e-mail link to a de-identified REDCap (Research Electronic Data Capture) questionnaire. Variables, including awareness and use of continuous glucose monitoring (CGM) and insulin pumps, were summarized descriptively using frequencies and percentages and were compared across racial/ethnic groups, education level, and income using Pearson χ2 or Fisher exact tests. The study included 116 participants, most of whom (62%) were White, elderly Medicare recipients. Compared with White participants, those of racially/ethnically minoritized groups were less likely to be aware of CGM (P = 0.013) or insulin pumps (P = 0.001). Participants with a high school education or less were also less likely to be aware of insulin pumps (P = 0.041). Interestingly, neither awareness nor use of CGM or insulin pumps was found to be associated with income. This cross-sectional analysis suggests that racially/ethnically minoritized groups and individuals with lower education have less awareness of CGM or insulin pumps.