Continuous Insulin Infusion Research Articles

Saved by Insulin! Continuous Intravenous Insulin Infusion as an Adjunctive Treatment for Refractory Hyperkalaemia

Intravenous insulin infusion which is used in treatment of hyperglycaemic emergencies can cause hypokalemia. We report a case of how this disadvantage was utilised to save a patient with life threatening hyperkalaemia. A 46-year-old lady with diabetes mellitus and chronic kidney disease (CKD) presented with breathlessness for 3 days. She had been taking excessive durian for 5 days before admission. Her medications included atenolol. On examination, she was severely bradycardic with pulse rate of 35 beats per minute. She had clinical features of fluid overload. Her renal profile showed elevated urea (17.5 mmol/l) potassium (7.8 mmol/l) and creatinine (322 umol/l). Electrocardiograph (ECG) showed junctional bradycardia. Despite counselling, she declined renal replacement therapy. Various potassium lowering therapies were given including regular nebulised salbutamol, calcium polystyrene sulfonate, intravenous furosemide, and regular insulin chase. After 5 rounds of insulin chases, potassium level remained markedly elevated at 8.2 mmol/l. When she finally consented, haemodialysis was performed. 9 hours post haemodialysis, potassium level was 7.6 mmol/l. While waiting for a next session of haemodialysis, fixed rate intravenous insulin infusion (0.1 unit/kg/hour) was given with concurrent dextrose fluids. Blood glucose was monitored hourly. 15 hours later potassium dropped to 5 mmol/l. ECG changes resolved with resolution of hyperkalemia. She did not require further haemodialysis. Patients with CKD should be cautious with durian intake as it is rich in potassium and may lead to severe hyperkalemia. This case highlights a novel use of continuous fixed-rate insulin infusion for treatment of refractory hyperkalemia when all else fails.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S8

Improved glycaemia during the Covid-19 pandemic lockdown is sustained post-lockdown and during the "Eat Out to Help Out" Government Scheme, in adults with Type 1 diabetes in the United Kingdom.

AimsThe majority of studies report that the Covid-19 pandemic lockdown did not have a detrimental effect on glycaemia. We sought to explore the impact of lockdown on glycaemia and whether this is sustained following easing of restrictions.MethodsRetrospective, observational analysis in adults and children with type 1 diabetes attending a UK specialist centre, using real-time or intermittently scanned continuous glucose monitoring. Data from the following 28-day time periods were collected: (i) pre-lockdown; (ii) during lockdown; (iii) immediately after lockdown; and (iv) a month following relaxation of restrictions (coinciding with Government-subsidised restaurant food). Data were analysed for times in glycaemic ranges and are expressed as median (IQR).Results145 adults aged 35.5 (25.8–51.3) years with diabetes duration of 19.0 (7.0–29.0) years on multiple daily injections of insulin (60%) and continuous insulin infusion (40%) were included. In adults, % time in range (70-180mg/dL) increased during lockdown (60.2 (45.2–69.3)%) compared to pre-lockdown (56.7 (43.5–65.3)%; p<0.001). This was maintained in the post-lockdown time periods. Similarly, % time above range (>180mg/dL) reduced in lockdown compared to pre-lockdown (p = 0.01), which was sustained thereafter. In children, no significant changes to glycaemia were observed during lockdown. In multivariable analysis, a greater increase in %TIR 3.9-10mmol/L (70-180mg/dL) during lockdown was associated with higher levels of deprivation (coefficient: 4.208, 95% CI 0.588 to 7.828; p = 0.02).ConclusionsGlycaemia in adults improved during lockdown, with people from more deprived areas most likely to benefit. This effect was sustained after easing of restrictions, with government-subsidised restaurant eating having no adverse impact on glycaemia.

Comparison between Continuous Regular Insulin Infusion and Single Dose Subcutaneous Long Acting Insulin Injection in Intensive Care Unit

Background: Stress-induced hyperglycemia is a common metabolic disorder in Intensive Care Unit (ICU) cases (30-60%) in diabetic and non-diabetic patients. It is related to increased rates of mortality and morbidity. Objective: The aim of the current work was to compare between glycemic control in single dose long-acting subcutaneous insulin glargine injection and standard continuous regular insulin infusion in the same critical case. Patients and methods: This prospective clinical study period was 72 hours for every patient and conducted on 111 patients aged 20-70 years with targeted blood glucose (BG) level ranging from 100 to 200 mg/dl using a different calculated dose of standard insulin infusion according to conventional sliding scale for the 1st 24hr of the study before conversion into insulin glargine single dose injection with 1-hour washout transition period. Results: APACHE II score was significantly higher in “Uncontrolled hyperglycemia” group in comparison to “Uncontrolled hypoglycemia” group (P=0.030) but insignificantly different between “Controlled” group and “Uncontrolled hyperglycemia” group and between “Controlled” group and “Uncontrolled hypoglycemia” group. Daily units of insulin and mean BG level at 1st day were significantly lower in “Uncontrolled hypoglycemia” group in comparison to “Controlled” group (P=0.002 and 0.002 respectively) and “Uncontrolled hyperglycemia” group (P=0.004 and 0.006 respectively) but insignificantly different between “Controlled” group and “Uncontrolled hyperglycemia” group. While mean BG level was insignificantly different among the three groups at 2nd day, it was insignificantly different between “Controlled” group and “Uncontrolled hyperglycemia” group at 3rd day. Conclusion: It could be concluded that the use of 100% conversion single dose of long-acting insulin glargine for control of hyperglycemia in critical ICU patients can be considered as an accepted good alternative to the classic use of continuous regular insulin infusion.

Acute Occlusion of the Lower Limb Artery Associated with Hyperosmolar Hyperglycemic Nonketotic Coma in a Patient with Amyotrophic Lateral Sclerosis: A Case Report

A 61-year-old man with amyotrophic lateral sclerosis (ALS) on tracheostomy positive pressure ventilation was brought to the emergency room due to decreased consciousness. He was diagnosed with hyperosmolar hyperglycemic nonketotic coma (HHNC) with severe systemic hypotension. He exhibited an adequate response to treatment of continuous intravenous insulin infusion and fluid replacement. On the third day, he developed acute limb ischemia due to extensive occlusion from the left common iliac artery to the femoral artery.

Dynamic changes in insulin requirements with post-operative time using bedside artificial pancreas to maintain normoglycemia without hypoglycemia after cardiac surgery.

It is difficult to manage postoperative blood glucose levels without hyperglycemia and hypoglycemia in cardiac surgery patients even if continuous intravenous insulin infusion is used. Therefore, the insulin requirements for maintaining normoglycemia may be difficult to evaluate and need to be elucidated. In this single-center retrospective study, 30 adult patients (age 71.5 ± 9.0years old, men 67%, BMI 22.0 ± 3.1kg/m2, diabetes 33%) who underwent cardiac surgery and used bedside artificial pancreas (STG-55) as a perioperative glycemic control were included. We investigated the insulin and glucose requirements to maintain normoglycemia until the day after surgery. The bedside artificial pancreas achieved intensive glycemic control without hypoglycemia under fasting conditions for 15h after surgery (mean blood glucose level was 103.3 ± 3.1mg/dL and percentage of time in range (70-140mg/dL) was 99.4 ± 2.0%). The total insulin requirement for maintaining normoglycemia differed among surgical procedures, including the use of cardiopulmonary bypass during surgery, while it was not affected by age, body mass index, or the capacity of insulin secretion. Moreover, the mean insulin requirement and the standard deviationof the insulin requirements were variable and high, especially during the first several hours after surgery. Treatment using the bedside artificial pancreas enabled intensive postoperative glycemic control without hypoglycemia. Furthermore, the insulin requirements for maintaining normoglycemia after cardiac surgery vary based on surgical strategies and change dynamically with postoperative time, even in the short term.

Gender-Specific Risk Factors for the Development of Retinal Changes in Children with Type 1 Diabetes.

The aim of the study was to determine gender-specific risk factor sets which could influence optical coherence tomography (OCT) results in children with type 1 diabetes (T1D). Material and Methods: 175 children with T1D without symptoms of diabetic retinopathy were enrolled, but 330 eyes were used for the final analysis (168 children, mean age 12.81 ± 3.63 years, diabetes duration 4.59 ± 3.71 years). The multivariate regression models for retinal thickness (foveal FT, and parafoveal PFT) and vascular densities (superficial and deep) were carried out separately for both genders using all metabolic and demographic parameters. Results: In the statistically significant multiple regression models for all analyzed OCT parameters for both genders, pH at the onset of diabetes were in existence, as well as for retinal thickness current HbA1c. Duration of continuous insulin infusion (CSII) was an important factor in all parameters, except PFT. For the girls, the most significant factors were daily insulin dose, uric acid, and triglycerides, but for the boys, it was serum creatinine, systolic pressure, and free thyroxine level. Conclusions: We detected significant risk factors set for development of OCT parameters changes, and they were not identical for both genders. Current metabolic control, diabetic ketoacidosis at the disease onset, serum creatinine and longer use of CSII are the most important factors for retinal thickness and vessel densities in both genders in children with type 1 diabetes. For the girls, elements of metabolic syndrome (uric acid and triglycerides) and parameters of insulin amount were more pronounced.

Hypoglycemia in a Surgical Intensive Care Unit.

Glycemic control is an important aspect of critical care because derangements are associated with morbidity and mortality. Patients at highest risk for hypoglycemia in the surgical intensive care unit (SICU) are incompletely described by existing literature. Our objective was to delineate this high-risk patient population in our SICU. In this single-center, retrospective, observational study, SICU patients admitted from June 1, 2019 to July 31, 2020 with ≥1 episode of hypoglycemia (blood glucose <60mg/dL) were included. There were 41 hypoglycemic events in 27 patients, comprising an incidence of 1.5% among SICU patients. The most common admission diagnoses were cirrhosis (n = 13, 48%), polytrauma (n = 12, 44%), multisystem organ failure (n = 11, 41%), diabetes mellitus (n = 9, 33%), and soft tissue infection (n = 8, 30%). Four high-risk populations were identified: patients in multisystem organ failure (MSOF) (n = 11, 41%); those who were nil per os (NPO) (n = 10, 37%); patients receiving long acting subcutaneous insulin, for example, Lantus (n = 3, 11%); and those on continuous intravenous insulin infusions (n = 3, 11%). After multi-disciplinary peer review, most hypoglycemic events (n = 16, 59%) were deemed iatrogenic. Hypoglycemia is rare in surgical critical care. When it does occur, patients are typically in MSOF, NPO, on long acting subcutaneous insulin or continuous insulin infusions, have soft tissue infections, or have acute or chronic liver failure. Increased vigilance with frequent blood glucose monitoring in these high-risk patients may reduce the risk of hypoglycemia in the SICU.

Root cause determination of intraperitoneal catheter obstructions: Insulin amyloid aggregates vs foreign body reaction

Continuous intraperitoneal insulin infusion, from an implanted insulin pump connected to a catheter that delivers insulin directly to the peritoneal cavity has many clinical advantages for patients with Type 1 diabetes. However, the ongoing incidence of catheter obstructions remains a barrier to the widespread use of this therapy. To date, the root cause of these obstructions remains unknown. Here, a two-year clinical investigation was conducted, along with the development of an animal model to enable a mechanistic investigation into this issue. This novel animal model was able to mimic the catheter obstructions that occur in patients and, fortuitously, at an accelerated rate. This model allowed for independent assessment of each potential cause associated with catheter obstructions to help identify the root cause. Both macroscopic and microscopic analysis were conducted with regards to the onset and progression of catheter obstructions, along with monitoring of insulin delivery. Interestingly, although insulin aggregation occurs in insulin pumps and insulin aggregates were found in some catheter obstructions, insulin is unlikely to be the root cause, since obstructions also occurred in the control groups where only diluent (no insulin) was administered to the animals. Inflammatory cells, different phenotypes of fibroblasts, as well as collagen were observed in all obstructed catheters explanted from the patients and the animals. The presence of these cells and collagen is indicative of a typical foreign body reaction. In addition, the dynamic change in the fibroblasts with respect to morphology, phenotype, and spatial distribution suggests that tissue irritation-mediated epithelial to mesenchymal transition plays a role in catheter obstructions.

195-OR: A Comparison of Inpatient Glycemic Control Using Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Persons with Type 1 Diabetes

Background: Continuous subcutaneous insulin infusion (CSII) therapy is increasingly being used in the outpatient setting, but there is little known information about its efficacy in the inpatient setting. This study compares inpatient glycemic control of persons with type 1 diabetes (T1D) using CSII, multiple daily injections (MDI), or both. Method: This retrospective chart review assessed the glycemic control of adult patients with T1D who used CSII, MDI or a combination of both during their hospitalization between January 1, 2017 and December 31, 2019. Those who were pregnant and/or treated with continuous intravenous insulin infusion were excluded. Variables were summarized descriptively using means and frequencies. Continuous variables were compared across groups using the ANOVA or Kruskal-Wallis test, and categorical variables were compared using the Fisher’s Exact test. Results: We analyzed records of 65 patients who were mostly male (53.8%) and white (72%) with a mean age of 51.7 ± 16.0 years. The mean hemoglobin A1c was 7.80 ± 1.08%. Though not statistically significant, both mean blood glucose and proportion of hyperglycemic events (proportion of blood glucose measures &amp;gt; 300 mg/dL) were lowest in the CSII group. Mean blood glucose for CSII, MDI, and both was 172.88 ± 40.14, 195.40 ± 43.90, and 199.50 ± 49.99 mg/dL, respectively (p=0.17). The proportion of hyperglycemic events for CSII, MDI, and both was found to be 0.11 ± 0.11, 0.26 ± 0.20, and 0.27 ± 0.27, respectively (overall p=0.0267, pairwise comparisons not significant). Conclusion: Glycemic control of patients with CSII is not significantly different than patients with MDI or a combination of both in persons with T1D, thus suggesting that patients can remain on CSII therapy while inpatient. Disclosure Y. Ye: None. S. Izard: None. A. Myers: None.

The Peruvian Experience: New-Onset Diabetes Presenting With Diabetic Ketoacidosis in Patients With COVID19 Infections

Introduction: Data has emerged about patients with T2DM may experience DKA and HHS if infected with SARS-CoV-2. There is limited data about new-onset diabetes in patients with COVID-19. We describe a case series of three Peruvian patients with new onset diabetes presenting with DKA who remained insulin dependent several months after infection resolution. Case 1: A 59-year-old man with no significant past medical history and normal glucose presented with fever and dyspnea for five days. He was hospitalized with hypoxemic respiratory failure and tested positive forCOVID19. Hypoxemia improved with supportive care, but on day three, he became lethargic, tachycardic, and tachypneic with 95% oxygen saturation on room air. Biochemistry revealed an anion gap metabolic acidosis with pH 7.3, bicarbonate 10 mmol/L (22–28), β-hydroxybutyrate 5.4 mmol/L (<0.5), and glucose 679 mg/dL. He was treated with continuous insulin infusion. After DKA resolved, he was transitioned to basal-bolus insulin and remained insulin-dependent during outpatient follow-up. Case 2: A 49-year-old man in good health prior to admission, was transferred to our hospital for acute respiratory failure and positive testing for SARS-CoV-2. Two days later he became confused, tachycardic, and tachypneic with 90% oxygen saturation. DKA was diagnosed based on a pH 7.1, bicarbonate 8 mmol/L, β-hydroxybutyrate 5 mmol/L and glucose 625 mg/dL. He was transferred to the ICU for continuous insulin infusion. After resolution of his DKA, subcutaneous insulin was started. Preadmission hemoglobin A1c was 4.5%. He remained on insulin post hospital discharge. Case 3: A 33-year-old man with normal glucose prior to admission was transferred to our hospital from an outpatient office with a two-day history of dyspnea and altered sensorium. He was tachycardic and tachypneic with 96% oxygen saturation on 3L nasal cannula. He tested positive for SARS-CoV-2. DKA was diagnosed with glucose 690 mg/dL, bicarbonate 4 mmol/L, serum β-hydroxybutyrate 5.8 mmol/L and pH 6.6. He was resuscitated with intravenous fluids and an insulin infusion was started. DKA resolved after 5 days and he was discharged home on subcutaneous insulin. He remained insulin-dependent on follow-up. Conclusion: New-onset diabetes with DKA due to SARS-CoV-2 is increasingly recognized, and beta-cell dysfunction can be permanent, resulting in insulin-dependent diabetes. Accordingly, our patients remained insulin-dependent several months post discharge.

SARS-CoV-2 Trigger in Severe Insulin Resistance With Acute Haemolytic Crisis in Diabetes and Glucose-6-phosphate Dehydrogenase Deficiency

Background: We report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as trigger for increased insulin resistance and severe haemolytic crisis in a male with type 2 diabetes mellitus and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinical Case: A 64-year-old man (BMI 25kg/m2, weight 75kg) with past medical history of type 2 diabetes mellitus (on metformin and sitagliptin; glycated haemoglobin 51 mmol/mol, n<42mmol/mol), hypertension, G6PD deficiency and gout was admitted to hospital with COVID pneumonitis and type 1 respiratory failure giving 5 days’ history of cough, shortness of breath, fatigue and tiredness. As per hospital guidelines, the patient was treated with amoxicillin/clavulanate 625mg three times daily and doxycycline 100mg once daily. Hydroxycholoroquine was not given in view of G6PD deficiency. There was no evidence of diabetic ketoacidosis and a short-acting insulin sliding scale was initiated at 2U/hr. Continuous positive pressure ventilation was offered for next 72 hours, however the patient failed to improve and required transfer to intensive care unit for intubation and mechanical ventilation. Computer tomography scan of pulmonary artery excluded embolism. The patient was fed via nasogastric tube post intubation. On day 8, the patient experienced a sudden drop in haemoglobin levels from 132 g/dl on day 1 to 68 g/dl, requiring multiple blood transfusions. The blood results demonstrated evidence of haemolysis with a rise in total and direct bilirubin and lactate dehydrogenase levels. The peripheral blood smear showed numerous bite cells with polychromasia suggesting an acute haemolytic crisis in the context of G6PD deficiency. A medication review revealed no evidence of drug-induced haemolysis. Later the patient was started on dexamethasone 6mg once daily (day 11) and on remdesivir 100mg once daily (day 15). During this time, the patient’s insulin infusion requirements had progressively increased from 2U/hr to 8U/hr (equivalent to 192 units/24 hr). On day 22, the patient’s clinical condition deteriorated with septicaemia requiring extended course of antibiotics. At this time, continuous insulin infusion was stopped and intermediate acting insulin (insulatard 36U twice daily; later increased to 48U twice daily) was started. In the next 10 days, the patient made good clinical recovery from sepsis with stable haemoglobin and blood sugar levels. He was extubated and transferred for rehabilitation. The patient was successfully weaned off insulin in the community with optimal diabetes control. Conclusion: This is a case demonstrating the possible role of SARS-CoV-2 in increased insulin resistance and severe haemolytic crisis on background of diabetes and G6PD deficiency.

Diabetic Ketoacidosis With Alpelisib

Background: Hyperglycemia is a frequently reported adverse effect of alpelisib, an isoform specific phosphoinositide 3 kinase inhibitor, which is recently approved for use in hormone receptor positive advanced or metastatic breast cancer. Though two patients in clinical trials with alpelisib developed diabetic ketoacidosis (DKA), there have been no case reports to date characterizing this complication after drug approval. We present the first case of DKA in patients on alpelisib therapy.Clinical Case: A 55-year-old woman with a history of hormone-receptor positive metastatic breast cancer was started on treatment with fulvestrant and alpelisib. The patient did not have any previous history of diabetes nor gestational diabetes, though she had evidence of prediabetes prior to starting treatment. Patient was non-obese and had a family history of type 2 diabetes. Baseline hemoglobin A1c was 5.6% (n <5.7%) with impaired fasting glucose of 108 mg/dl (n<105 mg/dL) immediately prior to starting therapy. One week after starting alpelisib, she presented to the emergency center in diabetic ketoacidosis. Initial laboratory evaluation showed serum glucose 690 mg/dl, anion gap metabolic acidosis, with undetectable serum bicarbonate and ketonuria. C-peptide on hospital day 1 was found to be 2.8 ng/ml (n 0.5 - 3.4 ng/ml) with a concurrent glucose of 479 mg/dl. GAD65 and Islet Antigen 2 antibodies were negative. Diabetic ketoacidosis quickly resolved with continuous insulin infusion and stopping alpelisib. The patient was able to come off all insulin therapy prior to discharge and was discharged on metformin with adequate glycemic control.Conclusions: Current manufacturer guidelines for alpelisib recommend screening for diabetes mellitus at baseline and monitoring blood glucose and/or fasting plasma glucose weekly for the first two weeks of treatment and monthly thereafter. However, patients with no pre-existing history of diabetes mellitus may be at risk for life-threatening hyperglycemic crises which may develop within a week of initiation of alpelisib and more frequent monitoring may be indicated. The hyperglycemic effect of alpelisib appears to be reversible upon stopping the drug.

DKA in Diet-Controlled Patient With Type 2 Diabetes and ESRD Precipitated by Acute COVID-19

Type 2 diabetes mellitus (T2DM) is the main factor for the global rise in end stage renal disease (ESRD), accounting for about 45% of the dialysis patient population in United States. Although T2DM is a common cause for ESRD, it is uncommon for well controlled T2DM patients on dialysis to develop DKA. The COVID-19 pandemic has highlighted infections as a precipitating cause of diabetic ketoacidosis (DKA) and stresses the importance of optimal glycemic control. We report a case of a previously diet controlled patient with T2DM and ESRD admitted with DKA and acute COVID-19. 46-year-old male with diet controlled T2DM, HIV (human immunodeficiency virus) on HAART (highly active antiretroviral therapy), ESRD secondary to HIV associated nephropathy was admitted from an outpatient dialysis unit with vomiting, chills and body aches. He was on metformin monotherapy prior to dialysis initiation. Regular self-monitored blood glucoses ranged 80-130mg/dl with HbA1C of 6% one month prior. Lab tests on admit revealed serum glucose 499mg/dl, elevated anion gap 21mmol/L, potassium 3.5mmol/L (3.5–5.0), HbA1C: 14.7%, elevated beta-hydroxybutyrate 5.6mmol/L(normal:<=0.4), CD4 count 500 (489–1457/µL) with an undetectable HIV viral load however COVID-19 polymerase chain reaction was detectable. He was managed with cautious fluid resuscitation requiring a total of one-liter normal saline, higher potassium dialysate (3K+), and continuous insulin infusion with resolution of abdominal symptoms and DKA. No other infections or precipitating factors were found and acute COVID-19 infection was managed symptomatically. He was discharged on basal bolus insulin regimen on day seven of admit. Up to a third of patients with diabetes on dialysis do not require anti-hyperglycemic therapy, such as our case. Potential factors leading to reduced insulin requirements include reduced renal insulin clearance,reduced renal gluconeogenesis, protein-energy wasting, reduced body weight and accumulation of uremic toxins (guanidino compounds postulated to act as biguanide agents). Our case highlights that acute COVID-19 can precipitate DKA in previously well controlled T2DM patients on hemodialysis while being aware of the need for cautious fluid and potassium administration due to lack of osmotic diuresis in anuric dialysis patients. Close self-monitoring of blood glucose should be emphasized in patients withT2DM with ESRD, including diet controlled T2DM patients, in order to reduce hyperglycemic emergencies and inpatient admissions especially during COVID-19 pandemic.

Glucose-6-phosphate Dehydrogenase Deficiency Induced Haemolysis in Male With Newly Diagnosed Diabetes During Diabetic Ketoacidosis Treatment: A Case Report

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency could be a risk factor for diabetes, as suggested by various epidemiological data, but still a matter of debate. The occurrence of haemolysis during diabetes crises was reported in patients with G6PD deficiency, furthermore the fall in glucose level during the treatment of hyperglycemia is suggested as a possible cause for hemolysis in G6PD deficiency. We reviewed the mechanisms that may link the two diseases. Clinical Case: A 19-year-old male, with G6PD deficiency, presented to the emergency department in our institution with history of generalised weakness, epigastric pain, nausea, and vomiting. He gave history of polyuria, polydepsia and weight loss over a period of two weeks. Diagnosis of DM was confirmed by laboratory tests that showed a mild DKA: arterial pH 7.28, HCO3 18 mmol/l, plasma glucose 21 mmol/l, urinary ketones ++, and hemoglobin 16.1 g/dl (12.0–15.0 g/dl). DKA was treated according to DKA guidelines. Ketoacidosis remission was achieved two days after rehydration and treatment with continuous intravenous insulin infusion (0.05–0.1 IU/kg). The patient then started on subcutaneous intensive insulin injection therapy, three times daily before meals and once before bedtime. Fasting and post-prandial blood glucose levels decreased to 7-8mmol/L, and 10 –13 mmol/l respectively. On day 4, the patient developed dizziness while he was taking a bath, On examination he was pale and had icterus, however, the vital signs and systemic examination were normal, blood tests revealed a hemolytic anemia as follows: (normal values): Hemoglobin 9 g/dl (12.0–15.0 g/dl), reticulocytes 8.5% (0.5–1.5%), total bilirubin 82 umol/l (0–20 umol/l), unconjugated bilirubin 58 umol/l (3–15 umol/l), By the 7th day, hemoglobin levels had fallen to the lowest value of 8.3, then gradually raised to 10.2 g/dl, 2 weeks later, hemoglobin electrophoresis was normal, Coombs test was negative. G6PD activity was below 300 U/L (reduced activit<600) with two separate measurements. The patient had no bacterial infections and had not ingested haemolytic drugs. Hemolysis ceased spontaneously and hemoglobin increased gradually. Conclusion: G6PD deficiency and diabetes mellitus could aggravate each other, and In patients at risk of G6PD deficiency screening of the enzyme activity should be considered following diabetes decompensation, and in case of G6PD deficiency, it is advisable to correct plasma glucose level gradually to avoid the rapid drop in glucose availability, which may cause hemolysis in these patients.

Nivolumab-induced hypophysitis followed by acute-onset type 1 diabetes with renal cell carcinoma: a\xa0case report

BackgroundImmune checkpoint inhibitors have recently become widely used for the management of advanced cancer patients. During the development of immune checkpoint inhibitors (ICPIs), it was quickly recognized that they are associated with autoimmune or autoinflammatory side effects. These toxicities are known as immune-related adverse events (irAEs): common endocrine irAEs include hypophysitis and thyroid dysfunction, and uncommon irAEs include type 1 diabetes mellitus (T1DM).Case presentationA 62-year-old Japanese man with metastatic renal cell carcinoma was treated with sunitinib followed by the 10th cycle of treatment with the ICPI nivolumab. He had already had thyroiditis and hypophysitis due to these anti-cancer drugs. On admission, he showed an extremely elevated plasma glucose level (601 mg/dl) and a low C-peptide level, and was diagnosed with acute T1DM. The patient was treated with intravenous fluid infusion and continuous insulin infusion. On the second day, he was switched to multiple daily injections of insulin therapy. Since these treatments, his blood glucose levels have been stable and he has been treated with an additional 10 ICPI treatments for renal cell carcinoma for over a year.ConclusionsTreatment with ICPIs is expected to increase in the future. There may be cases in which their use for cancer treatment is inevitable despite the side effects. As long as treatment with ICPI continues, multiple side effects can be expected in some cases. It is important to carefully observe the side effects that occur during ICPI treatment and to provide appropriate treatment for each side effect.

Impact of Body Habitus on the Outcomes of Pediatric Patients With Diabetic Ketoacidosis.

To determine whether obese and overweight pediatric patients with new onset diabetic ketoacidosis (DKA) treated with continuous infusion insulin have increased time to subcutaneous insulin initiation or adverse events as compared with patients with normal body habitus. A retrospective, cohort study was designed that included patients 2 to 18 years of age admitted with new onset DKA who received continuous infusion insulin from January 1, 2011, to December 31, 2017. Patients were stratified according to BMI percentile with the primary outcome of time to initiation of subcutaneous insulin. Secondary endpoints included time to minimum beta-hydroxybutyrate, and incidence of hypoglycemia or other adverse events. A total of 337 patients (46.6% male, 9.6 ± 3.8 years of age) met study criteria. Patients were classified by body habitus as obese (7.7%, n = 26), overweight (7.1%, n = 24), normal body weight (58.8%, n = 198), or underweight (26.4%, n = 89), based on BMI percentile. Most patients were initiated on insulin at 0.1 unit/kg/hr (86.7%) for 16.7 ± 7.0 hours. Time from continuous infusion insulin initiation to subcutaneous insulin was not different between body habitus groups, nor was hypoglycemia or the use of mannitol (p > 0.05). Median time to lowest beta-hydroxybutyrate was greater for obese (26.4, IQR [13.9, 41.9]) and overweight (32.4, IQR [18.3, 47.0]) groups than for normal body habitus patients (16.5, IQR [12.3, 23.8]) (p < 0.05). Time to subcutaneous insulin and adverse events was not associated with body habitus, but obese and overweight patients may have delayed beta-hydroxybutyrate clearance.

Diabetes mellitus in Anaesthesia - Optimal Blood Sugar Control in the Perioperative Phase

Uncontrolled high blood sugar can be dangerous for diabetics throughout the perioperative period - in particular, when blood glucose levels exceed a threshold of 250 mg/dl or HbA1c levels are higher than 8.5 - 9%. In such cases, all elective surgery should be withheld to minimize the risk of severe complications. Due to their cardiovascular comorbidities, diabetics are commonly overrepresented in hospitals, tend to require inpatient care for an extended period of time, and suffer from higher mortality rates. In order to reduce negative outcomes, blood glucose levels should be targeted to 140 - 180 mg/dl on intensive care units or during surgery. Current literature suggests that non-critically ill diabetics should be treated with rapid-acting insulin analogues subcutaneously in operating theatres, whereas critically ill patients should receive continuous intravenous insulin infusions using a standardized protocol. In summary, this review can give a hand in dealing with diabetics during the perioperative period and offers guidance in controlling blood sugar levels with the help of oral antidiabetic drugs and insulin.

Accuracy of a Low-Cost Continuous Subcutaneous Insulin Infusion Pump Prototype: In Vitro Study Using Combined Methodologies.

Considering that infusion devices are safety-critical systems, the main goal of this paper is to evaluate the infusion accuracy and precision of a low-cost insulin infusion pump prototype, using two different methodologies. The first one used a microgravimetric method adapted from IEC60601-2-24, and the second estimated the displacement of the syringe plunger in response to programmed infusions. The low-cost prototype resulted in a compact and functional device with good accuracy. The prototype infused the programmed fluid doses with an average error of 2.2%. The percentage of infusions within ± 5% accuracy was 42.50 and of 84.17% for the ± 15% limit. The developed miniaturized mechanical system presented functionality, precision, and accuracy when coupled to the electronic system, responded well to repeatability tests. Additionally, the results from in vitro tests demonstrated that the performance of the device is satisfactory and comparable to commercial continuous insulin infusion pumps. This study presents a low-cost prototype as a candidate to be used by type 1 diabetic patients in Brazil and developing countries, especially in the context of public health.

Metformin Associated Lactic Acidosis and Euglycemic Diabetic Ketoacidosis: A Case Report

Diabetic ketoacidosis is a common complication of diabetes traditionally defined as a triad of hyperglycemia (>250 mg/dl), anion gap acidosis, and positive serum or urine ketones. However, a rare complication which requires a high level of clinical suspicion is euglycemic diabetic ketoacidosis. Patients will still present with an anion gap acidosis and positive serum or urine ketones but then will have a blood glucose level less than 200 mg/dl. We present a case with a patient who presented with metformin-associated lactic acidosis and euglycemic ketoacidosis (MALKA). Our patient presented with seizure-like activity, slurred speech, and diffuse weakness when laboratory results revealed a high anion gap metabolic acidosis with concomitant metabolic and respiratory alkalosis. She was noted to have an elevated lactate which resolved with sodium bicarbonate. However, her anion gap persisted, and she was positive for urine ketones suggesting the possible diagnosis of euglycemic DKA. The patient was started on a continuous infusion of insulin with dextrose which subsequently helped resolve her persistent anion gap acidosis. Despite a standardized protocol for treatment of diabetic ketoacidosis, MALKA remains a challenging diagnosis to make without high clinical suspicion and ruling out other possible diagnoses. The goal of this case is to enhance clinician’s diagnostic framework for anion gap metabolic acidosis.

Can early hyperglycemia affect the morbidity/mortality of very low birth weight premature infants?

The study aimed to examine the effect of early hyperglycemia on the morbidity/mortality of very low birth weight premature infants. This retrospective study included all premature infants with gestational age ≤32 gestational weeks, hospitalized at the Department of Intensive Neonatal Care, Clinical Center Kragujevac, during the period 2017-2019. Hyperglycemia was defined as glycemia of ≥12 mmol/l in one measurement, or > 10 mmol/l in two measurements, at repeated intervals of 2-4 hours. Glycemia was determined from capillary blood, using a gas analyzer of Gem Premier 3000, during the first 7 days of life. Continuous intravenous insulin infusion was administered after ineffective glucose restriction at glycemic values of > 14 mmol/l. Patients with normoglycemia (41/72 (56.94%)) and hyperglycemia (31/72 (43.06%)) did not differ in gender, gestational age, mode of delivery and antenatal administration of steroids, while birth weight had a tendency to be lower in the hyperglycemic group (p=0.052). Hyperglycemia was significantly associated with a low APGAR score at the fifth minute (p=0.048), necrotizing enterocolitis (p=0.011), and shorter duration of mechanical ventilation (p=0.006). Hyperglycemia was associated with significantly more frequent fatal outcomes (35.5%) when compared with the normoglycemic group (4.9%). Accordingly, these patients required inotropic (r=0.036) and insulin therapy (r < 0.001) more often. Retinopathy of prematurity, bronchopulmonary dysplasia and sepsis did not correlate with hyperglycemia in our study. Intraventricular hemorrhage of the first degree was more often associated with normoglycemia in premature infants on prolonged mechanical ventilation while more severe intracranial hemorrhage was more common in the hyperglycemic group but did not result in statistical significance due to the small number of patients. Monitoring glucose levels in the blood of very low birth weight premature infants is clinically important because abnormalities in glucose homeostasis can have serious short-term and long-term consequences.