Insulin Requirement In Patients Research Articles

One-Year Effect of Elexacaftor/Tezacaftor/Ivacaftor Therapy on HbA1c Levels and Insulin Requirement in Patients with Insulin-Dependent Cystic Fibrosis-Related Diabetes: A Retrospective Observational Study.

The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T3mo), 6 months (T6mo) and 12 months (T12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T3mo and T6mo, but not at T12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment.

Effectiveness and safety of glucose-lowering drugs as an adjunct to insulin therapy in Chinese patients with type 1 diabetes: a retrospective, observational study.

To assess the real-world impact of glucose-lowering drugs (GLDs) as an adjunct to insulin in Chinese patients with type 1 diabetes (T1DM). This dual-center, observational, retrospective study included 121 T1DM patients receiving GLDs as adjuncts and 56 participants with insulin-only drugs as comparators. Glycated hemoglobin A1c (HbA1c), daily insulin dosage, fasting blood glucose (FBG), postprandial blood glucose (PBG), nocturnal blood glucose (NBG) and the difference in trough and peak blood glucose levels on the same day (Δ TP) were assessed at baseline and at the end of the study. In total, HbA1c decreased by 1.14% in the GLD+insulin group (p < 0.0001) and 0.36% in the insulin-only group (p = 0.0423, mean adjusted difference, -0.09% [95% CI, -0.55 to 0.37]). The total daily insulin concentration was reduced by 7.34 U per day in the GLD+insulin group vs. 5.55 U per day in the insulin-only group (mean adjusted difference, -2.32 U [95% CI, -4.97 to 0.33]). In particular, among patients with fasting C-peptide levels < 17 pmol/L, the total daily insulin concentration was significantly reduced by 9.22 U vs. 5.09 U per day (mean adjusted difference, -3.84 [95% CI, -6.85-0.84]; p = 0.0129). There were no notable differences in the other glycemic indices between the two groups. A gradual downward trend in changes in glycemic outcomes was observed among patients treated with various combinations of metformin, acarbose, and dipeptidyl peptidase 4 inhibitor (DPP-4i). Similar reductions in the daily insulin dose were also detected in most of the GLD+insulin group in addition to the DPP-4i-only group. No severe hypoglycemia was induced by additional GLDs. The use of additional GLDs tends to improve glycemic outcomes and reduce insulin requirements in patients with T1DM. These results indicate that the use of GLDs as an adjunctive therapy may have been an effective treatment strategy among adults with T1DM in China.

Efficacy of Perioperative Infusion of N(2)-L-alanyl-L-glutamine in Glycemic Control for Patients With Uncontrolled Diabetes Mellitus Presented for Urgent Coronary Artery Bypass Surgery: A Randomized Controlled Trial

To evaluate the efficacy of preoperative glutamine infusion in reducing insulin requirements in patients with uncontrolled type 2 diabetes, defined as glycated hemoglobin (HbA1c) >7%, undergoing urgent coronary artery bypass graft (CABG) surgery. A randomized controlled trial. At Ain Shams University Hospital, Cardiothoracic Academy. Ninety-three patients (of both sexes) with uncontrolled diabetes presenting for urgent CABG were categorized into 2 groups. The dipeptiven group (n=46) was given an infusion of dipeptiven 1.5 mL/kg body weight dissolved in normal saline (200 mL) over 3 hours before surgery. The control group (n=47) received a normal saline infusion (200 mL). The dipeptiven group demonstrated statistically significant lower intraoperative (173.74 ± 19.97 mg/dL v 198.22 ±14.64 mg/dL) and postoperative (162.36 ±13.11 mg/dL v 176.13 ±14.86 mg/dL) mean blood glucose levels. In addition, dipeptiven infusion was found to reduce mean total insulin requirements intraoperatively by 3.64 ± 0.56 units/h and postoperatively by 37.109 ± 4.30 units/24 h in comparison to placebo (50.98 ± 16.55 units/24 h and 5.10 ± 2.28 units/h, respectively). A preoperative infusion of dipeptiven can contribute to ameliorating stress hyperglycemia in uncontrolled diabetic patients undergoing urgent CABG.

Multidisciplinary intensive lifestyle intervention improves markers of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes and obesity: a retrospective matched-cohort study

BackgroundThe prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing among patients with type 1 diabetes (T1D) paralleling the increasing prevalence of obesity among this population. However, little is known about the impact of intensive lifestyle intervention (ILI) on NAFLD in patients with T1D.MethodsUsing Hepatic Steatosis Index (HSI), a noninvasive surrogate predictor of NAFLD, we retrospectively evaluated 88 adult patients with T1D and obesity after one year of participating in a 12-week ILI program in real-world clinical practice. Using the NAFLD guidelines of the American Association for the Study of Liver Diseases (AASLD), we excluded 11 participants. We matched the remaining ILI cohort (age 43 ± 12 years, females 65%, diabetes duration 22 ± 9 years, A1C 8.2 ± 0.9%, body weight 101 ± 17 kg, BMI 35.3 ± 4.9 kg/m2) in 1:1 ratio with a similar cohort of patients with T1D and obesity who received standard diabetes care (SC) at the same practice and during the same period. Matching criteria included: sex, age, BMI, A1C and duration of T1D. HSI [8 + ALT/AST + BMI (+ 2 if female, + 2 if T2D)] was calculated at baseline and after 12 months of intervention.ResultsAt baseline, HSI was similar between the two cohorts (46.2 ± 6.1 in the ILI cohort and 44.9 ± 5.7 in the SC cohort). After 12 months, the ILI group lost an average of 5.6 ± 2.7 kg (5.8%, p < 0.05) while the SC group maintained their baseline body weight (p < 0.001 between groups). HSI decreased significantly from baseline in the ILI group (-2.7 ± 1.1, p = 0.01), but did not change in the SC group (0.6 ± 0.9, p = 0.53, p < 0.001 between groups). Percentage of patients with high likelihood of NAFLD diagnosis decreased from 100% at baseline to 88.3% in the ILI group, and was 10.4% less compared to SC (p < 0.01). Total daily insulin dose decreased in the ILI cohort compared to the SC cohort (-6.1 ± 4.2 versus 1.34 ± 4.3 units/day, p < 0.01).ConclusionsTwelve weeks of ILI improved HSI and decreased total daily insulin requirements in patients with T1D and obesity at one year. Short-term ILI should be implemented in the management of NAFLD for obese patients with type 1 diabetes.

Determinants of Insulin Therapy among Women with Gestational Diabetes Mellitus: A Cross-Sectional Study

ABSTRACT Background: Gestational diabetes mellitus (GDM) is a common complication in pregnancy that occurs during the second half of pregnancy. In the majority of patients, medical nutritional therapy (MNT) alone is sufficient to achieve the glycemic goal. Aim: To evaluate the clinical and biochemical factors that predict the need for insulin therapy in women with GDM. Materials and Methods: Between March 2020 and November 2021, an analytic cross-sectional study was conducted on 127 women diagnosed with GDM at their final antenatal visit. Multivariate logistic regression was used to determine the variables associated with the likelihood of insulin requirement in patients with GDM. Results: To achieve glycemic control, 56.7% of the study population required insulin treatment. Fasting glucose, pre-conceptional body mass index (BMI), parity, and third-trimester glycated hemoglobin levels were all higher in the insulin-treated group (P = 0.00, 0.01, 0.01, and 0.02), respectively. Fasting glucose level is the main determinant of insulin use in patients with GDM (odds ratio [OR]: 1.110; 95% confidence interval [CI]: 1.001–1.191; P = 0.004). Conclusions: Fasting glucose level is the most important predictor of the need for insulin therapy.

Relationship of Vitamin D level with insulin dosage required based on insulin therapy protocol.

The deficiency of vitamin D amongst Iranian people is high and also is related on hyperglycemia. This study aims to evaluate the association of vitamin D levels with the required dose of insulin prescribed based on an insulin therapy protocol in critical condition patients admitted to intensive care unit (ICU), in an investigation based in Iran. This cross-sectional study was performed on patients who required insulin due to hyperglycemia. The relationship between serum vitamin D level and the required dose of insulin prescribed based on insulin therapy protocol in this group of patients was investigated. A total of 172 patients with a mean age of 46.93 ± 31.9 years were included in this study. Across the included participants, 78.8% of patients had vitamin D deficiency, 11.9% had insufficient vitamin D and 9.3% had normal vitamin D levels. There was a significant difference in mean blood sugar between the vitamin D deficiency group and the normal group. Vitamin D levels were also significantly higher in men than women. Furthermore, the HbA1C hemoglobin level in patients with Vitamin D deficiency was significantly higher compared to the group with normal levels of vitamin D. Our findings suggest that decreased vitamin D is associated with increased blood sugar and insulin requirements in patients admitted to ICU. Women are at a higher risk for vitamin D deficiency. We hope that these findings may help inform relevant treatment strategies.

A Systematic Review of the Effects of Sleeve Gastrectomy and Gastric Bypass on Type 2 Diabetes Control in the Middle East

Objective: The study aimed to explore the outcome of sleeve gastrectomy and gastric bypass in middle east patients with type 2 diabetes through the assessment of the weight trajectory postoperatively and its effect on the glycaemic control assessed by HbA1c. Where applicable, investigate the impact of sleeve gastrectomy and gastric bypass on the reduction of polypharmacy and postoperative Insulin requirements in patients with type 2 diabetes. Research Design and Methods: PubMed and Science Direct databases were searched. The obtained studies were screened for the title and abstract, followed by full-text reading and retrieved relevant studies. The data was extracted from the relevant papers using a united form according to the inclusion criteria. The articles' quality was assessed and critically appraised, and a narrative synthesis was conducted. Results: Eight studies met the inclusion criteria comprised the final review, and all had positive results. Four articles studied sleeve gastrectomy outcomes, and four compared sleeve gastrectomy and gastric bypass. All studies showed weight reduction postoperatively calculated as BMI, Total Weight Loss, or Excess Weight Loss sustained up to 5 years. The studies which assessed glycaemic control showed improvement of glycaemic parameters, reduction of HBA1C, and some achieved remission among prediabetes and diabetes patients. The review also indicated the reduction and cessation of antidiabetic medications following surgical interventions, which is attributed to achieving diabetes remission. A long-term follow-up cohort with a large sample size revealed that HBA1C reduction was more enunciated and sustained following gastric bypass in patients with diabetes. Conclusion: Sleeve Gastrectomy and Gastric Bypass positively affect type 2 diabetes control among obese adult patients in the Middle East. Both surgical interventions lead to weight reduction and improvement of glycaemic parameters postoperatively up to 5 years .........

Short-Term Effectiveness and Reduction in Insulin Requirements in Patients With Type 2 Diabetes Treated With IdegLira in a Real-World Setting.

BackgroundType 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting.MethodsAn observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events.Results67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline.ConclusionsThis real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.

The Relationship Between Insulin Use And Increased Mortality In Patients With COVID-19 And Diabetes: A Meta-Analysis

ABSTRACT Purpose: The purpose of this study is to review observational studies on the effect of insulin use and mortality in patients with COVID-19 and diabetes. Methods: A systematic literature search was performed using the PubMed, Medline, EMBASE, and Cochrane Library databases. The meta-analysis was performed using a random effects model, and I2 was applied to evaluate heterogeneity. Sensitivity and subgroup analyses were also performed. Results: Overall, 1,338 patients over six studies were ultimately included. Insulin use was related to a higher risk of death in diabetic patients with COVID-19 compared to those who did not use insulin (odds ratio: 2.59, 95% confidence interval: 1.66–4.05; P < .0001; I2: 57%). Conclusions: This meta-analysis revealed a correlation between insulin usage and increased mortality in diabetic patients with COVID-19. These results showed that insulin requirement in patients with COVID-19 and diabetes might indicate a poor prognosis.

121-LB: Glucose- and Glucagon-Lowering Effect of a Single Oral Leptin Dose in Type 1 Diabetes Patients

Recent understandings of the role of leptin in glucagon and glucose homeostasis, have flagged it as a target for management of type 1 diabetes (T1D). While historically thought to be involved in long-term regulation of appetite and energy expenditure, leptin is now known to regulate food absorption, mucus secretion, intestinal motility and inflammatory processes. Leptin was shown to directly inhibit glucose uptake and reduce glucagon levels and insulin requirements in NOD mice, to ameliorate hyperglycemia in a T1D mouse model, and reduce insulin requirements in patients with insulin-resistant diabetes. Leptin-based drugs are currently only available in injectable forms, and suffer from a short half-life in the circulation. ORMD-0701 is an oral leptin drug, specially formulated to protect the active ingredient from degradative forces in the gut and enhance its uptake across the intestinal mucosa. This first-in-human study assessed the short-term effects of a single ORMD-0701 dose (3 mg leptin) administered to fasting patients with T1D. Patients on an insulin pump and with glucose levels &amp;gt;100 mg% and &amp;lt;280 mg%, received an ORMD-0701 (n=7) or placebo (n=3) capsule. Basal insulin pump rates were then lowered to 50% of the regular program and blood glucose, glucagon and leptin levels were monitored for 3 h. Glucagon area under the curve 30-120-min post-treatment (AUC30-120) was 0.60 ng*min/L lower than baseline values, while it rose by 0.69 ng*min/L in the placebo group. Similar trends were recorded for glucose AUC30-120 measures, with an 0.43 mmol*min/L decrease from baseline AUC in the active group versus a 0.24 mmol*min/L increase in the placebo group. By the end of the monitoring period, glucose and glucagon levels returned to baseline levels in all patients. No significant changes in blood leptin levels were detected in either cohort. These preliminary findings set the stage for further assessment of oral leptin and its impact on normalizing the insulin-glucagon balance in patients with T1D. Disclosure M. Kidron: Employee; Self; Oramed Pharmaceuticals, Inc., Stock/Shareholder; Self; Oramed Pharmaceuticals, Inc. S. Perles: Employee; Self; Oramed Ltd. R. Weiss: Consultant; Self; Lilly Global Health Partnership, Medtronic, Speaker’s Bureau; Self; Novo Nordisk.

Basal insulin requirement in patients with type 1 diabetes depends on the age and body mass index.

Aims/IntroductionTo investigate the basal insulin requirement in patients with type 1 diabetes who are on multiple daily injections (MDI) and to assess the patient characteristics that affect the percent of total daily basal insulin dose to the total daily insulin dose (%TBD/TDD).Materials and MethodsThe subjects of this study were 67 inpatients with type 1 diabetes who were served diabetic meals of 25–30 kcal/kg standard body weight during several weeks of hospitalization. The basal insulin requirement was adjusted to keep the blood glucose level from bedtime to before breakfast within a 30 mg/dL difference. The bolus insulin dose before the meal was adjusted to keep the blood glucose level below 140 and 200 mg/dL before and 2 h after each meal, respectively. The total daily insulin dose (TDD), the percent of total daily basal insulin dose (TBD) to TDD (%TBD/TDD), and clinical characteristics were collected.ResultsThe median (Q1, Q3) of TDD was 33.0 (26.0, 49.0) units, and the %TBD/TDD was 24.1 ± 9.8%. The %TBD/TDD was positively correlated with the body mass index (BMI) and negatively correlated with the age at the onset and at the examination according to a univariate analysis. However, the %TBD/TDD was dependent on the BMI (β = 0.340, P = 0.004) and the age at examination (β = −0.288, P = 0.012) according to the multiple regression analysis.ConclusionsThe average %TBD/TDD in patients with type 1 diabetes on MDI was approximately 24% under inpatient conditions. The basal insulin requirement was dependent on the BMI and the age at examination.

Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin

The role of integrins, in particular αv integrins, in regulating insulin resistance is incompletely understood. We have previously shown that the αvβ5 integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) regulates cellular uptake of fatty acids. In this work, we evaluated the impact of MFGE8 on glucose homeostasis. We show that acute blockade of the MFGE8/β5 pathway enhances while acute augmentation dampens insulin-stimulated glucose uptake. Moreover, we find that insulin itself induces cell-surface enrichment of MFGE8 in skeletal muscle, which then promotes interaction between the αvβ5 integrin and the insulin receptor leading to dampening of skeletal-muscle insulin receptor signaling. Blockade of the MFGE8/β5 pathway also enhances hepatic insulin sensitivity. Our work identifies an autoregulatory mechanism by which insulin-stimulated signaling through its cognate receptor is terminated through up-regulation of MFGE8 and its consequent interaction with the αvβ5 integrin, thereby establishing a pathway that can potentially be targeted to improve insulin sensitivity.

The excess insulin requirement in severe COVID-19 compared to non-COVID-19 viral pneumonitis is related to the severity of respiratory failure and pre-existing diabetes.

IntroductionSevere COVID‐19 has been anecdotally associated with high insulin requirements. It has been proposed that this may be driven by a direct diabetogenic effect of the virus that is unique to SARS‐CoV‐2, but evidence to support this is limited. To explore this, we compared insulin requirements in patients with severe COVID‐19 and non‐COVID‐19 viral pneumonitis.MethodsThis is a retrospective cohort study of patients with severe COVID‐19 admitted to our intensive care unit between March and June 2020. A historical control cohort of non‐COVID‐19 viral pneumonitis patients was identified from routinely collected audit data.ResultsInsulin requirements were similar in patients with COVID‐19 and non‐COVID‐19 viral pneumonitis after adjustment for pre‐existing diabetes and severity of respiratory failure.ConclusionsIn this single‐centre study, we could not find evidence of a unique diabetogenic effect of COVID‐19. We suggest that high insulin requirements in this disease relate to its propensity to cause severe respiratory failure in patients with pre‐existing metabolic disease.

An Insulin Resistance Case Report: Uncontrolled Hyperglycaemia in type 1 Diabetic Patient Post COVID-19 Infection

COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late December 2019 in Wuhan, China, and has spread to become a pandemic with over 100 million confirmed cases and still growing. The infectious nature and hence, high hospitalization rates and intensive care admissions are resulting in high mortality rates. Alarmingly, COVID-19 infection and virus-induced respiratory dysfunction poses a serious threat to patients with chronic illnesses such as diabetes, Asthma, COPD and obesity. COVID-19 patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity, but this showed up in COVID-19 positive cases. Here, we report the case of transitory moderate increase in insulin requirement in a type 1 diabetic (T1D) patient who was previously well controlled in the absences of any medical conditions known to be a causative factor. We collected the data and compared total insulin daily requirement against pre-meal glycemia and blood gas results to reflect insulin resistance and multiple DKA events related to trials of multiple oral hypoglycemic agents and GLP1 analogue as potential target for intervention in addition to insulin therapy and low carb diet.

Evaluating the Impact of Glucagon-Like Peptide-1 Receptor Agonists on Metabolic Changes in Patients With Type 2 Diabetes on High-Dose Insulin.

Studies involving the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide have shown reductions in hemoglobin A1c (HbA1c), weight, and insulin requirements in patients with type 2 diabetes mellitus (DM2) requiring high-dose insulin therapy. The effect of the class of GLP-1 RAs on these parameters is unknown. A retrospective cohort analysis was conducted in patients with DM2 where a GLP-1 RA was added to high-dose insulin therapy. The primary composite outcome was the change from baseline to 9 months in HbA1c, weight, and insulin dose. GLP-1 RA therapy was associated with a significant reduction in HbA1c from baseline (-0.9%; P = 0.022). Weight and insulin dose were not significantly reduced from baseline. There was a moderate effect of individual agents on these outcomes, but no significant reductions were seen due to the small sample size. Generalizability of these findings may be limited by the characteristics and size of the study population. The effect of GLP-1 RA therapy on HbA1c may be attributed to the medication class. The effect of individual agents on weight and insulin requirements needs further investigation.

Extremely high-dose insulin requirement in a diabetic patient with COVID-19: a case report

BackgroundDetailed description of hyperglycemia management in diabetic patients infected with SARS-CoV-2 remain limited, although patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity. Here, we report the case of an extreme and transitory insulin requirement episode in a type 2 diabetic patient presenting an acute respiratory distress syndrome caused by SARS-CoV-2.Case presentationA 57-year-old man resident in Geneva, Switzerland, previously known for type 2 diabetes for 3 years was admitted for an aggravation of his dyspnea. His type 2 diabetes was treated only with metformin and his latest Hb1Ac was 6.1%. Chest CT SCAN showed a bilateral multilobar ground-glass opacification. Twenty-four hours after his admission he presented a worsening of dyspnea and severe hypoxemia requiring a transfer to the intensive care unit rapidly followed by oro-tracheal intubation for mechanical ventilation support. A bronchoalveolar lavage was performed and test of SARS-CoV-2 by RT-qPCR assay was positive. At day 3, he presented a rapidly progressive insulin requirement at a rate of up to 50 units/hour intravenous insulin aspart. Despite the high insulin doses, he maintained an elevated plasma glucose level at 270 mg/dL on average. His extremely high-dose insulin requirement “resolved” at day 9, and the insulin infusion rate was rapidly reduced.ConclusionsThis case may reflect a specific and profound impact of SARS-CoV-2 on metabolic homeostasis, in particular in diabetic patients that appear more prone to complications of COVID-19 infection. Yet, the mechanisms behind this remain to be elucidated. The optimal management of hyperglycemia of diabetic patients infected with SARS-CoV-2 has yet not be defined, however insulin remain the mainstay of treatment approach. Report of extreme dysregulation of chronic conditions such as diabetes in patients with COVID-19 may help clinicians to better take care of patients during the pandemic of SARS-CoV-2.To the best of our knowledge this is the first description of extremely high-dose insulin requirement in patient with COVID-19.

2191-PUB: Challenging the 50%/50% Basal/Bolus Insulin Ratio Rule: Have We Been Wrong? A Cross-Sectional Study

There is a generally-held belief that the ratio between basal and bolus insulin requirements in patients using insulin therapy should be 50%/50%. Yet, it appears this belief was based on a small study with healthy individuals, which may not be applicable to patients with insulin deficiency. To assess the validity of the rule we followed patients with type 2 diabetes treated with basal-bolus insulin therapy that has been frequently adjusted by a technology-based titration service. To keep glycemia stable, the service adjusts insulin dosage at least weekly and thus treatment closely tracks insulin requirements. We performed a cross-sectional study, accumulating data on N=306 patients over an average±SD period of 3.4±1.7 years. Insulin titrations occurred every 6.8±1.5 days to enable HbA1c maintenance at 7.2±0.7%. In 74.8% of the patients the average basal insulin fraction was less than 50% of total daily dose of insulin, and in about a third it was less than 38% (Figure). Additionally, the basal fraction did not remain stable in each patient over time (Figure). In 79.7% of the patients, it changed more than 20% and in 50% more than 29.8% (e.g., basal fraction changes in a single patient would range between 20% and 50% over time). In patients with type 2 diabetes treated with insulin, basal-bolus ratio is not 50%/50% and it changes over time. Thus, this ratio should not be used as a treatment guide. Disclosure I. Hodish: Stock/Shareholder; Self; Hygieia. M. Willis: Employee; Self; Hygieia. S. Sritharan: None. E. Bashan: Employee; Self; Hygieia. Stock/Shareholder; Self; Hygieia.

SAT-LB93 Rapid Reduction of Insulin Requirement in a Hyperglycemic Patient Treated for Hemophagocytic Lymphohistiocytosis

Background: Hemophagocytic lymphohistiocytosis (HLH) is life-threatening disorder of immune dysregulation involving macrophage and T-cell activation resulting in massive cytokine release causing multi-organ dysfunction. Similar release of cytokine products from fat tissue is associated with obesity-related insulin resistance. Our case presentation is an example of HLH and insulin resistance, two conditions with overlapping pathophysiology, occurring simultaneously. Clinical Presentation: A 17-year-old male, with no history of hyperglycemia, underwent renal transplant due dysplastic kidneys. He received 500mg IV methylprednisolone during surgery followed by a prednisone taper starting at 70mg daily. Serum glucoses post-transplant ranged from 97 to 129 mg/dL. Three weeks post-transplant he was admitted for fever and dehydration. BMI on admission was the 85th percentile. Serum glucose was 371 mg/dL without ketosis. He started on insulin therapy, requiring 60 units per day (0.8 units/kg). It was suspected his new-onset diabetes was due to his immunosuppressant regimen (prednisone 50mg daily, tacrolimus) and/or acute illness. With persistent fevers and negative infectious workup, there was concern for HLH. The diagnosed was confirmed with ferritin level of 65,962 ng/mL (27-265), hemoglobin 6.5 gm/dL, platelets 88,000, triglycerides 765 mg/dL, soluble IL-2 receptor 2,717 u/mL (45 - 1,105). For HLH treatment, he received methylprednisolone 800 mg daily x 3 doses. During this time his insulin requirements increased to 188 units per day (3.6 units/kg). He was transitioned to dexamethasone 20mg daily. His insulin requirements increased over the next 72 hours to 388 units per day (5.2 units/kg). He was found to be positive for Ehrlichiosis, a known precipitant of HLH. Doxycycline therapy was initiated for a 14 day course. One week into his doxycycline course his ferritin had decreased to 999 ng/mL. He remained on dexamethasone 20 mg daily but developed severe hypoglycemia to 29 mg/dL with altered mental status. All insulin therapy was held. Fasting glucoses over the next 4 days ranged from 94-154 mg/dL and post-prandial glucoses 116-288 mg/dL. He discharged home with only short acting insulin for glucoses above 250 mg/dL, which he did not require. Case Lessons: Cytokine release from macrophages is implicated in the pathology of both HLH and insulin resistance associated with obesity. Glucocorticoids used to treat HLH can also exacerbate insulin resistance. Providers should be aware of the risk of hyperglycemia and large insulin requirements in patients with HLH, and the potential for rapid reduction of insulin needs as HLH is successfully treated.

Perioperative Glycemic Control in Patients who Underwent Cardiac Transplantation and Effect on the Outcome at Discharge in a Tertiary Care Centre.

Objectives:To study the glycemic status and insulin requirements in patients who underwent cardiac transplantation and to compare it among patients with and without diabetes mellitus. To compare preoperative glycemic status and perioperative insulin requirements with the outcome.Methods and Materials:The retrospective data of the glycemic status of patients before and after cardiac transplantation were collected and analyzed. Different variables like HbA1c, creatinine, age, BMI, and glycemic status were compared with the outcome.Results:A total of 18 patients with a mean age of 46.72 ± 16.94 years (mean ± SD) and a median age of 48.5 years underwent cardiac transplantation. The mean preoperative glycosylated hemoglobin (HbA1c) was 8.75 ± 2.15% (72 ± 2.36 mmol/mol) and 5.82 ± 0.45% (40 ± 4.89 mmol/mol) in patients with and without diabetes mellitus, respectively. The mean insulin requirement of insulin on postoperative days 0, 1, 2, and 3 was 1.396, 0.503, 0.490, and 0.537 (IU/kg/day) in patients with diabetes, whereas in patients without diabetes mellitus it was 1.955, 0.561, 1.19, and 0.61 (IU/kg/day), respectively. The mean insulin requirement at the time of discharge was 0.698 ± 0.43 IU/kg/day (mean ± SD) and 1.285 ± 1 IU/kg/day (mean ± SD) (p = 0.36) in patients with and without diabetes mellitus, respectively (p = 0.53, 0.11, 0.41, and 0.32, respectively). There was no association with the outcome when analyzed with different variables like HbA1c, creatinine, BMI, age, hemoglobin, insulin requirements, and glycemic status.Conclusions:Perioperative glycemic control is crucial for successful cardiac transplantation irrespective of diabetic status.

Combination treatment of autologous bone marrow stem cell transplantation and hyperbaric oxygen therapy for type 2 diabetes mellitus: A randomized controlled trial

The objective of this study was to compare standard treatment versus the combination of intrapancreatic autologous stem cell (ASC) infusion and hyperbaric oxygen treatment (HBOT) before and after ASC in the metabolic control of patients with type 2 diabetes mellitus (T2DM). This study was a prospective, randomized controlled trial. The combined intervention consisted of 10 sessions of HBOT before the intrapancreatic infusion of ASC and 10 sessions afterwards. ASCs were infused into the main arterial supply of the pancreas to maximize the presence of the stem cells where the therapeutic effect is most desired. A total of 23 patients were included (control group = 10, intervention group = 13). Age, gender, diabetes duration, number of medications taken, body weight and height, and insulin requirements were recorded at baseline and every three months. Also, body mass index, fasting plasma glucose, C-peptide, and HbA1c, C-peptide/glucose ratio (CPGR) were measured every three months for one year. HbA1c was significantly lower in the intervention group compared with control throughout follow-up. Overall, 77% of patients in the intervention group and 30% of patients in the control group demonstrated a decrease of HbA1c at 180 days (compared with baseline) of at least 1 unit. Glucose levels were significantly lower in the intervention group at all timepoints during follow-up. C-peptide levels were significantly higher in the intervention group during follow-up and at one year: 1.9 ± 1.0 ng/mL versus 0.7 ± 0.4 ng/mL in intervention versus control groups, respectively, p = 0.0021. CPGR was higher in the intervention group at all controls during follow-up. The requirement for insulin was significantly lower in the intervention group at 90, 180, 270, and 365 days. Combined therapy of intrapancreatic ASC infusion and HBOT showed increased metabolic control and reduced insulin requirements in patients with T2DM compared with standard treatment.