Insulin Injection Sites Research Articles

Recurrence of Non-Hodgkin Lymphoma at the Insulin Injection Site: Case Report

This study sheds light on the effect of insulin, insulin-like growth factors (IGF), and their signalling receptors (IR and IGF-1R) on the progression of lymphoma. We report a case of a 64-year-old male with type 2 diabetes mellitus and a prior diagnosis of diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with chemotherapy and local radiotherapy. Incredibly, four years post-treatment, the patient's DLBCL relapsed in the subcutaneous fatty tissue adjacent to the deltoid muscle of both the proximal left and right upper extremities, which were the sites he used to inject insulin. Insulin/IGF dysregulation can lead to tumour growth via angiogenesis. This mechanism is not limited to lymphoma and may contribute to the development of various types of cancer. While it is possible that DLBCL may have developed at the injection site either coincidentally, as a result of chronic inflammation, or potentially due to other factors that promote tumour growth, as we suggest in our case presentation, it is beneficial to emphasise the importance of tumour screening in diabetic patients, especially those receiving insulin injections. We therefore believe that regular screening of the insulin injection site should be included in routine consultations for these patients.

12339 Rotating Insulin Injection Sites Isn't Enough: A Challenging Case Of Insulin-Induced Lipoatrophic Panniculitis

Abstract Disclosure: J. Hand: None. S. Nemiroff: None. C. Zmijewski: None. C.J. Levy: None. Introduction: Insulin-induced localized lipoatrophy is a rare phenomenon that involves the loss of subcutaneous adipose tissue around sites of insulin injections, and it often presents as a deep, retracted scar on the skin. Its prevalence has dropped significantly given improvements in recombinant and purified insulin and its analogs, from 55% to more recently 1-2%. Lipoatrophy can cause erratic absorption of insulin, leading to suboptimal glycemic control and hypoglycemia. The pathophysiology is not completely understood but is thought to be immune-mediated. Treatment options are limited and often focus on rotating injection sites or changing the type of insulin, though some case reports alternatively describe using corticosteroid injections. Here, we report an unusual case where a patient developed a form of early, localized lipoatrophy called lipoatrophic panniculitis due to insulin. Clinical Case: A 28-year-old male with a 13-year history of type 1 diabetes presented for insulin optimization. The patient was using multiple daily injection (MDI) insulin therapy and later an insulin pump, with careful infusion site rotation. Seven years later, he experienced issues with his pump sites, developing nodules and bruises that became painful and caused labile glycemic control. He underwent dermatologic, rheumatologic, and allergic workup with two biopsies confirming insulin-induced lipoatrophic panniculitis. Immunosuppressive and varying insulin regimens were unsuccessful. Hydroxychloroquine and methotrexate showed limited improvement with intolerable gastrointestinal side effects. Trials of hydrocortisone in his insulin infusion or topical clobetasol with tacrolimus provided no benefit. Various MDI regimens with different concentrations of lispro, aspart, faster aspart, glargine, detemir, and degludec were tried; all elicited varying degrees of pain with suboptimal glycemic response. A supervised trial of inhaled insulin was associated with bronchospasms. An implantable insulin pump was sought through clinical trials but was not feasible due to eligibility. Ultimately, he was successfully referred for pancreas transplantation due to his labile and complicated diabetes, but the procedure was complicated by allograft thrombosis and failure. He is currently awaiting a second transplant. Clinical Lesson: There are few reports of patients with insulin-induced lipoatrophic panniculitis in the literature. It is an important differential to consider for a patient that is having unexpected glycemic excursions, and it is equally as challenging to select an adequate management regimen. Treatment is limited and a broad range of options need to be considered. When these patients fail mainstay immunosuppressive, corticosteroid, and insulin-based management, pancreas transplantation may be considered as an alternative feasible treatment. Presentation: 6/1/2024

Impaired Awareness of Hypoglycemia and its Risk Factors among Diabetic Patients in Jazan, Saudi Arabia: A Cross-Sectional Study.

Impaired awareness of hypoglycemia (IAH) is related to a three- to sixfold increase in the risk of severe hypoglycemia in adults with type 1 diabetes mellitus (T1D). This study aimed to assess the prevalence of IAH and its risk factors and determine the frequency of hypoglycemic symptoms. This study aimed to assess the prevalence of IAH and its risk factors and determine the frequency of hypoglycemic symptoms. A cross-sectional study was conducted among T1D patients attending Jazan Endocrine and Diabetes Center in Jazan province, Saudi Arabia. A total of 151 patients participated, using the interview-based Clarke questionnaire, a validated eight-item questionnaire to evaluate IAH. Scoring four or more answers as reduced awareness categorizes the participant as having IAH. The prevalence of IAH was 25.2% among the T1D patients. IAH was significantly associated with body mass index (BMI; p = 0.034), occupation (p = 0.014), and blood glucose monitoring methods (p = 0.027). Shaking and sweating were the most commonly reported symptoms of hypoglycemia. A BMI of <25 kg/m2 was higher linked to hunger and speech difficulty compared to a BMI of ≥25 kg/m2 (p < 0.05). Changing the insulin injection site was associated with confusion, odd behavior, and speech difficulty (p < 0.05). Monitoring blood glucose four times daily was associated with sweating, odd behavior, and incoordination (p = 0.024) compared to monitoring less than four times daily (p < 0.05). A hemoglobin A1c (HbA1c) reading of ≥7 was linked to odd behavior compared to an HbA1c reading of <7 (p = 0.032). Patients committed to insulin injections were more likely to experience palpitations than non-committed patients (p = 0.038). Each one-unit increase in age, monitoring blood glucose, and income was associated with a decrease in the odds of IAH (OR of Age = 0.89, 95% CI: 0.83-0.95) (OR of income = 0.10, 95% CI: 0.01-0.55). Moreover, individuals with a Body Mass Index (BMI) greater than or equal to 25 (OR = 2.99, 95% CI: 1.13-8.25), employed individuals (OR = 18.2, 95% CI: 3.75-105), and diabetes duration of more than ten years (OR = 3.96, 95% CI: 1.31- 13.2) exhibited an increase in the higher risk of IAH. IAH was prevalent among T1D patients attending Jazan Endocrine and Diabetes Center. The main associated factors included BMI, blood glucose monitoring method, and occupation. Future research should investigate the underlying causes of the observed associations and explore strategies to enhance the awareness of hypoglycemia.

Insulin-induced Lipohypertrophy in a Patient with Type 2 Diabetes

Abstract Lipohypertrophy (LH) is a common side effect of insulin treatment in patients with diabetes, characterized by soft, benign nodules in the subcutaneous tissue. This case report describes the management of insulin-induced LH in a 66-year-old male with type 2 diabetes. The patient had been on a combination of oral antidiabetic agents (ODAs) and biphasic human insulin for 5 years, experiencing the symptoms of numbness, leg swelling, fatigue, and frequent hypoglycemic episodes. Upon examination, LH with skin pigmentation was observed at the insulin injection sites on both calves. The patient’s laboratory investigations revealed poor glycemic control with high glycated hemoglobin percentage. To address the condition, the patient was advised to change the injection site, use proper site rotation, and change the insulin needle daily. The insulin therapy was modified by switching to biphasic premixed analog insulin injected 5 min before meals using the insulin pen. In addition, ODAs were adjusted for better glycemic control. Following these interventions, the patient reported improved glucose levels and stable kidney function. This case report emphasizes the importance of early detection and appropriate management of insulin-induced LH through patient education and insulin therapy adjustments. Health-care providers should remain vigilant for LH and educate patients on proper injection practices to optimize diabetes management and prevent complications.

Atomic resolution structure of full-length human insulin fibrils

Patients with type 1 diabetes mellitus who are dependent on an external supply of insulin develop insulin-derived amyloidosis at the sites of insulin injection. A major component of these plaques is identified as full-length insulin consisting of the two chains A and B. While there have been several reports that characterize insulin misfolding and the biophysical properties of the fibrils, atomic-level information on the insulin fibril architecture remains elusive. We present here an atomic resolution structure of a monomorphic insulin amyloid fibril that has been determined using magic angle spinning solid-state NMR spectroscopy. The structure of the insulin monomer yields a U-shaped fold in which the two chains A and B are arranged in parallel to each other and are oriented perpendicular to the fibril axis. Each chain contains two β-strands. We identify two hydrophobic clusters that together with the three preserved disulfide bridges define the amyloid core structure. The surface of the monomeric amyloid unit cell is hydrophobic implicating a potential dimerization and oligomerization interface for the assembly of several protofilaments in the mature fibril. The structure provides a starting point for the development of drugs that bind to the fibril surface and disrupt secondary nucleation as well as for other therapeutic approaches to attenuate insulin aggregation.

Unveiling Diabetes: Categories, Genetics, Diagnostics, Treatments, and Future Horizons.

Diabetes mellitus is a global epidemic affecting millions of individuals worldwide. This comprehensive review aims to provide a thorough understanding of the categorization, disease identity, genetic architecture, diagnosis, and treatment of diabetes. The categorization of diabetes is discussed, with a focus on type 1 and type 2 diabetes, as well as the lesser-known types, type 3 and type 4 diabetes. The geographical variation, age, gender, and ethnic differences in the prevalence of type 1 and type 2 diabetes are explored. The impact of disease identity on disease management and the role of autoimmunity in diabetes are examined. The genetic architecture of diabetes, including the interplay between genotype and phenotype, is discussed to enhance our understanding of the underlying mechanisms. The importance of insulin injection sites and the insulin signalling pathway in diabetes management are highlighted. The diagnostic techniques for diabetes are reviewed, along with advancements for improved differentiation between types. Treatment and management approaches, including medications used in diabetes management are presented. Finally, future perspectives are discussed, emphasizing the need for further research and interventions to address the global burden of diabetes. This review serves as a valuable resource for healthcare professionals, researchers, and policymakers, providing insights to develop targeted strategies for the prevention, diagnosis, and management of this complex disease.

Clues to the Design of Aggregation-Resistant Insulin from Proline Scanning of Highly Amyloidogenic Peptides Derived from the N-Terminal Segment of the A-Chain.

Insulin aggregation poses a significant problem in pharmacology and medicine as it occurs during prolonged storage of the hormone and in vivo at insulin injection sites. We have recently shown that dominant forces driving the self-assembly of insulin fibrils are likely to arise from intermolecular interactions involving the N-terminal segment of the A-chain (ACC1-13). Here, we study how proline substitutions within the pilot GIVEQ sequence of this fragment affect its propensity to aggregate in both neutral and acidic environments. In a reasonable agreement with in silico prediction based on the Cordax algorithm, proline substitutions at positions 3, 4, and 5 turn out to be very effective in preventing aggregation according to thioflavin T-fluorescence-based kinetic assay, infrared spectroscopy, and atomic force microscopy (AFM). Since the valine and glutamate side chains within this segment are strongly involved in the interactions with the insulin receptor, we have focused on the possible implications of the Q → P substitution for insulin's stability and interactions with the receptor. To this end, comparative molecular dynamics (MD) simulations of the Q5P mutant and wild-type insulin were carried out for both free and receptor-bound (site 1) monomers. The results point to a mild destabilization of the mutant vis à vis the wild-type monomer, as well as partial preservation of key contacts in the complex between Q5P insulin and the receptor. We discuss the implications of these findings in the context of the design of aggregation-resistant insulin analogues retaining hormonal activity.

Exploring the Diagnostic Value of High-Frequency Ultrasound Technology for Subcutaneous Lipohypertrophy in Diabetes Patients Receiving Insulin Injections.

This study aims to investigate the clinical application value of high-frequency ultrasound technology in diagnosing subcutaneous lipohypertrophy at insulin injection sites in diabetes patients. All diabetes patients treated in our hospital from January 2022 to January 2023 were selected as the study subjects. The incidence of subcutaneous lipohypertrophy was calculated at the end of the study period. All patients were screened, and those meeting the inclusion criteria were registered, and basic data were collected. Patients were screened for subcutaneous lipohypertrophy using conventional clinical examination (control group) and high-frequency ultrasound technology (study group). The study found that the incidence of subcutaneous lipohypertrophy in diabetes patients receiving insulin injections in our hospital from January 2022 to January 2023 was 80.99%. The average longitudinal diameter of subcutaneous lipohypertrophy in these patients was 11.66 (7.56, 21.44) mm, the transverse diameter was 12.04 (8.96, 18.29) mm, depth was (5.62±2.17) mm, and the area was 188.79 (76.85, 331.78) mm². The clinical detection rate in the study group was higher than that in the control group (P<0.05). The quantity of detected sites was greater in the study group compared to the control group (P<0.05). The incidence of subcutaneous lipohypertrophy in diabetes patients receiving insulin injections is relatively high clinically, and high-frequency ultrasound technology demonstrates significant potential in diagnosis. By providing high-resolution imaging and quantitative data, it effectively improves the clinical detection rate and clarifies symptoms. This technology is likely to become an important auxiliary tool in future diabetes treatment, providing more precise treatment plans for patients.

Hemorrhagic Shock Associated with a Subcutaneous Insulin Pump Catheter: First Time Reported Side Effect.

Continuous subcutaneous insulin infusion (CSII) systems, used to treat diabetes for over 40 years may improve glycemic control but also have rare major complications. We report the first hemorrhagic shock on the infusion site of an insulin pump, due to a rectus abdominis hematoma. An eighty-one years old woman with history of cardiovascular events and type 1 diabetes, presented with hemorrhagic shock due to a rectus abdominis hematoma rapidly constituted at the insulin injection site. The situation improved after conservative treatment (blood transfusions, IV fluids, replacement of the CSII with insulin injections). Contributive factors to this complication were overdose of anticoagulant, oversized insulin canula and cough. We recommend increased monitoring of patients using insulin pump with hemorrhagic risk factors. Specific education for the prevention and detection of signs of hemorrhage should lead patients to report this situation promptly, in order to avoid this life-threatening complication.

A Major Error in Insulin Injection Site

Insulin therapy is frequently essential for people with type 2 diabetes to attain glycemic control. Nonetheless, it is becoming more apparent that individuals with diabetes at times disregard correct insulin injection techniques and commit errors that usually result in uncontrolled glycemia. Here, we report the case of an 81-year-old male presented with uncontrolled glycemia. A detailed examination revealed that he was administering insulin at the incorrect injection site, which in turn resulted in inaccuracy in the dosage of insulin delivered subcutaneously. The case highlights an array of factors such as age, patient’s ability to self-manage insulin administration, nonexistence of a caregiver, and the extended period between in-person visits that contributed to insulin injection errors and eventually uncontrolled glycemia.

The impact of insulin induced lipohypertrophy on carotid intima-media thickness in patients with type 2 diabetes mellitus.

Lipohypertrophy (LH) is a major localized complication of insulin therapy. We aimed to investigate the association between insulin-induced LH and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (DM). A total of 75 patients with DM treated with insulin were included in this study. The insulin injection sites of the patients were evaluated by inspection and palpation and then radiologically with ultrasound. The CIMT of the patients was evaluated using ultrasonography. According to the guideline recommendation, the CIMT cutoff value was taken as 0.9 mm, and the patients were categorized into 2 groups according to the CIMT value and evaluated statistically. The presence of LH (CI: 1.379-30.000; OR = 6.432; P < .05), age (CI: 1.036-1.149; OR = 1091; P < .05), BMI (CI: 1.003-1.262; OR = 1.125; P < .05) and duration of DM (CI: 1.001-1.300; OR = 1.141; P < .05) were independent risk factors for high-CIMT in patients with DM. The most interesting result of this study was that the presence of LH was an independent risk factor for increased CIMT. According to this result, we think that LH may increase the risk of cardiovascular disease as well as being a complication that disrupts the blood glucose regulation of patients with DM and increases the cost of treatment.

Hypertrophic Keloid Formation in a Type 2 Diabetes Mellitus Patient (A Case Report)

Keloids are scars that extend beyond the original area of skin damage. They can develop after minor skin trauma in predisposed individuals. Many factors play a role in keloid scar formation, with certain systemic diseases being a risk factor for their development. Diabetes mellitus is a disease that affects a variety of organ systems including the skin. Multiple skin conditions have been implicated directly and indirectly with diabetes mellitus and their presence would often be a sign of insulin resistance or poor glycemic control. Here we present a case of hypertrophic keloid developing in a patient with Type 2 Diabetes Mellitus. The patient had no prior skin trauma, nor did she develop the lesions at the sites of insulin injection. This raises the question of whether hypertrophic keloids might be associated with diabetes mellitus and whether recommendations for DM screening and guidance on use of insulin injections in those patients should be put in place. Key words: Keloids, Hypertrophic, Diabetes, Insulin resistance

A Hypothesis on the Progression of Insulin-Induced Lipohypertrophy: An Integrated Result of High-Frequency Ultrasound Imaging and Blood Glucose Control of Patients.

To put forward a scientific hypothesis about the progression of insulin-injection-induced lipohypertrophy (LH) according to the high-frequency ultrasonic imaging of insulin injection sites and the blood glucose control of patients. A total of 344 patients were screened for LH by means of high-frequency ultrasound scanning. The results of their ultrasound examination were described in detail and categorized into several subtypes. Seventeen patients with different subtypes of LH were followed up to predict the progression of LH. To further verify our hypothesis, the effects of different types of LH on glycemic control of patients were observed by comparing glycated hemoglobin A1c (HbA1C) and other glycemic-related indicators. LH was found in 255 (74.1%) patients. According to the high-frequency ultrasonic imaging characteristics, LH can be categorized into three subtypes in general. Among all the LHs, the most common type observed was nodular hyperechoic LH (n = 167, 65.5%), followed by diffuse hyperechoic LH (n = 70, 27.5%), then hypoechoic LH (n = 18, 7.0%). At the follow-up after six months, all 10 patients with nodular hyperechoic LH had LH faded away. Of the five patients with diffuse hyperechoic LH, two had inapparent LH, and three had diffuse hyperechoic parts which had shrunk under ultrasound. No obvious changes were observed in the two cases of hypoechoic LH. Compared with the LH-free group, the mean HbA1C of the nodular hyperechoic LH group increased by 0.8% (9 mmol/mol) (95% CI:-1.394~-0.168, p = 0.005), that of the diffuse hyperechoic LH group increased by 2.0% (21 mmol/mol) (95% CI: -2.696~-1.20, p < 0.001), and that of the hypoechoic LH group increased by 1.5% (16 mmol/mol) (95% CI: -2.689~-0.275, p = 0.007). It was hypothesized that the earlier stage of LH is nodular hyperechoic LH. If nodular LH is not found in time and the patient continues to inject insulin at the LH site and/or reuse needles, LH will develop into a diffuse type or, even worse, a hypoechoic one. Different subtypes of LH may represent differences in severity when blood glucose control is considered as an important resolution indicator. Further studies are needed to confirm our hypothesis on the progression and reversion of insulin-induced lipohypertrophy.

Insulin-derived amyloidosis (insulin ball) and skin-related complications of insulin therapy

Skin-related complications of insulin therapy have long been a problem as a factor interfering with insulin therapy. Among the traditional skin-related complications, lipoatrophy and insulin allergy have decreased markedly with the development of insulin preparations, but lipohypertrophy is still common in insulin-treated patients. Recently, there have been more reports of a skin-related complication called insulin-derived amyloidosis or insulin ball. Insulin-derived amyloidosis is a condition in which injected insulin becomes amyloid protein and is deposited at the injection site. Insulin-derived amyloidosis causes poor glycemic control and increased insulin dose requirements, which are caused by decreased insulin absorption. Lipohypertrophy also decreases insulin absorption, but insulin-derived amyloidosis causes a more significant decrease in insulin absorption and has a greater clinical impact. Therefore, it is important to make a differential diagnosis between insulin-derived amyloidosis and lipohypertrophy, but sometimes it is difficult to distinguish the two and imaging studies are required. The diagnosis of insulin-derived amyloidosis is often difficult in the general practice, and its pathogenesis and prevalence have not been fully clarified. Recently, it has been reported that insulin-derived amyloidosis can be toxic, suggesting an association with minocycline use. The treatment of insulin-derived amyloidosis and lipohypertrophy is to avoid the site of amyloidosis or lipohypertrophy and inject insulin, but the dose of insulin injection should be reduced. Prevention of both insulin-derived amyloidosis and lipohypertrophy is important, and for this purpose, observations of the insulin injection site and instruction on appropriate insulin injection techniques are necessary, and multidisciplinary cooperation is extremely important.

Insulin-induced Lipo hypertrophy and factors affecting it in children and adolescents with type 1 diabetes mellitus: Review of Literature in the past 12 years

Lipohypertrophy (LD) is one of the most common complications of subcutaneous insulin injection. Many factors are convicted in the development and progress of LD in children with T1DM. Lipodystrophy can worsen glycemic control in these children. This review aimed at summarizing these important epidemiological and clinical data to clarify the different aspects of this abnormality and its predisposing factors that are necessary for prevention, early detection, and proper management. Methods: We searched PubMed, Google Scholar, Research Gate, and Scopus for research articles related to insulin-induced LD after 2010. 28 papers were found, reviewed, and analyzed. Results: The prevalence of LD varied greatly between 17% and 75% and was significantly affected by different risk factors. The pooled prevalence of LD in children and adolescents (16 studies) was 45.16 % while the pooled prevalence in adults was 41.3%. The prevalence of LD in children appeared to be relatively higher in children compared to adults. The most critical risk factors detected in these studies included: the longer duration of diabetes and the reuse of insulin syringe &gt; 5 times, lack of rotating insulin injection sites and or using a small area for injection, higher insulin dose/kg, the BMI, the location of injection (more LD in the abdomen, low level of patient education, higher insulin antibodies and poor control of diabetes. In addition, the method of detecting LD markedly affected the prevalence of LD. Conclusion: Improper insulin injection technique and longer duration of T1DM were the most important risk factors associated with LD. Children with LD have poorer glycemic control and require higher doses of insulin per kg compared to those without LD.

Lipohypertrophy prevalence and its associated risk factors in insulin-treated patients with type 2 diabetes in North Borneo, Malaysia.

Insulin-treated diabetes patients are at high risk of developing lipohypertrophy, which can negatively impact treatment outcomes. Early detection of lipohypertrophy is crucial to preventing blood glucose fluctuation. Unfortunately, this clinical issue is often overlooked by nurses, causing the development of vascular complications, which leads to an increase in the morbidity and mortality of the type 2 diabetes mellitus population. This study was conducted to identify lipohypertrophy prevalence and to establish the association between the presence of lipohypertrophy and its associated risk factors, including years on injection, total injection in a day, total insulin unit per day, often change needle, insulin injection site and move to a different area. This cross-sectional study included 128 patients with type 2 diabetes mellitus who received insulin therapy in an outpatient diabetic clinic. Questionnaires on socio-demographic and lipohypertrophy-associated risk factors were distributed among patients, and lipohypertrophy-assessment was done using a checklist. Descriptive statistics and Pearson Chi-square were used for statistical analysis. The prevalence of lipohypertrophy was 51.6% (95% CI: 42.6, 60.5). Swelling on fatty tissue (46.1%) exhibited the highest percentage of lipohypertrophy features during the assessment. Pearson Chi-Square revealed a significant relationship between the presence of LH and BMI categories (χ2 = 10.059, df = 3, p = 0.018), duration of injection (χ2 = 15.001, df = 3, p = 0.002), frequency of needle replacement (χ2 = 9.525, df = 3, p = 0.023) and rotation of injection site (χ2 = 5.914, df = 1, p = 0.015). The high prevalence of lipohypertrophy indicates a need for a prevention strategy. Thus, nurses should play an important role in educating patients regarding the proper administration of insulin injections and performing a routine lipohypertrophy assessment and health education on the correct method of insulin injection.

Injection Site Reaction to Various Insulins as Type III Allergy With Urticarial Vasculitis in a Patient With Type I Diabetes Mellitus.

Injection site reactions are defined as skin reactions at the injection site to drugs administered subcutaneously. Pathophysiologically, these reactions are based on different immunological mechanisms. We report the case of a 49-year-old patient with type 1 diabetes mellitus (first diagnosis in 1994 at the age of 23 years). Continuous subcutaneous insulin infusion using an insulin pump has been used for many years. The patient presented to the department of dermatology with progressive symptoms in the area of the insulin injection sites on the lower abdomen, accompanied by pain, burning, erythema, tenderness, and the formation of subcutaneous nodules. Previous attempts to use different insulins and to change the injection sites did not improve his symptoms. Furthermore, the symptoms appeared within hours after the insulin pump was attached, so that the injection site has to be changed as soon as every 48 hours. No anaphylactic shock was reported at any time. Multiple histological specimens were obtained from an older lesion on the abdomen as well as from test sites after standard allergological tests (prick and intradermal tests) of various insulins. Histologically, these biopsies showed the image of an extensive deep-reaching small vessel vasculitis with the aspect of an urticarial vasculitis and confirmed the diagnosis of an injection-site reaction that can be characterized as a type III hypersensitivity reaction.

Effect of Insulin Injection Techniques on Glycemic Control Among Patients with Diabetes.

Previous studies have shown that healthcare professionals rarely instruct patients about proper insulin injection techniques. This study aimed to assess the practices of insulin injection techniques among patients with diabetes treated and assess the effect of these practices on glycemic control. This cross-sectional study was conducted between November 2020 and February 2021. A random systematic sampling technique was used to recruit study subjects at specialist outpatient clinics. Subjects with type 1 or 2 diabetes mellitus who had been using insulin injections for at least a year were included in this study. A total of 298 subjects with type 1 diabetes and 553 with type 2 diabetes participated in this study. The mean age of patients with type 1 diabetes was 20.1 ± 10.4 years. The mean age of patients with type 2 diabetes was 58.6 ± 9.5 years. The median type 1 diabetes duration was 6.0 years, and median type 2 diabetes duration was 15.0 years. About 66.8% of patients with type 1 diabetes and 69.4% of patients with type 2 diabetes were rotating insulin injection sites. Almost 36.6% of patients with type 1 diabetes and 50.5% of patients with type 2 diabetes reported using the same insulin needle more than three times. The prevalence of lipohypertrophy was 57.0% among patients with type 1 diabetes and 55.5% among patients with type 2 diabetes. The absence of lipohypertrophy, rotation of insulin injection site, and total daily insulin dose ≤50 units were all independently significantly associated with better glycemic control. Insulin injection techniques were suboptimal among significant proportion of patients with diabetes in Jordan. Improper insulin injection technique, especially the rotation of injection sites and lipohypertrophy formation, was associated with uncontrolled blood glucose levels. Educational interventions that focus on insulin injection techniques among Jordanian patients with diabetes are strongly recommended.

LBSUN294 Insulin-induced Abdominal Acanthosis Nigricans From High Doses Of Insulin U-500

Abstract Introduction Dermatological complications associated with insulin therapy include lipoatrophy, lipohypertrophy, and acanthosis nigricans. We have a rare case of severe acanthosis nigricans from repeated insulin injection. Case A 63-year-old man with diabetes mellitus type 2 presented with an elevated blood glucose of 584mg/dL. He reported "high" glucose levels, despite adherence to his insulin regimen. He only injected insulin in his abdomen. Over 20 years, his insulin doses increased from Lantus 65 units BID and Humalog 35 units TID to Lantus units 110 BID and Humalog 65 units TID. It was later changed to U-500 at 160 units TID. His Hba1c ranged from 10.7% to 15.4%, most recently 13.6%. Physical examination revealed hyperpigmented and thickened plaques, localized to two large areas lateral to his umbilicus. During his hospital stay, insulin was administered on his arms and thighs. Glucose levels improved on Levemir 55 units daily and Lispro 20 units TID. He was discharged on Insulin U-500 40 units TID with instructions to avoid injecting on his abdomen and to rotate injection sites. Discussion Acanthosis nigricans is associated with insulin resistance or hyperinsulinemia. Insulin has a similar structure to insulin-like growth factor (IGF-1). At higher insulin concentrations, it can bind to IGF-1 receptors on keratinocytes and fibroblasts, leading to skin proliferation. Other suggested mechanisms include the involvement of fibroblast and epidermal growth factor. Histopathological findings show hyperkeratosis, papillomatosis, and thickened dermis. Immunochemical findings show positive IGF-1 antibodies in basal epithelial and prickle cell layers. In patients with poor glycemic control and increasing doses of insulin, it is important to assess for insulin-related skin changes. Besides routine visual inspection, skin thickening can be assessed by stroking the skin side-to-side in a sweeping motion instead of palpation. Conclusion Our patient with poorly type 2 diabetes required escalating doses of insulin over the years. He developed severe acanthosis nigricans on his abdomen leading to poor absorption of insulin. This case highlights the importance of routine visual inspection and tactile examination of insulin injection sites for skin changes, as well as repeated counseling regarding insulin site rotation.

Hypoglycemia Caused by Exogenous Insulin Antibody Syndrome: A Large Single-Center Case Series From China.

Exogenous insulin antibody syndrome (EIAS) can lead to unexpected and potentially life-threatening recurrent hypoglycemia. We aimed to better define autoimmune hypoglycemia caused by EIAS in patients with diabetes and shed light on the improvements in the identification and intervention for this rare but possibly life-threatening condition. We summarized the clinical characteristics of autoimmune hypoglycemia caused by EIAS in 23 patients with diabetes. Furthermore, we performed human leukocyte antigen (HLA) genotyping of 10 patients. We identified a high frequency of autoimmune comorbidities (21.7%), food or drug allergy (48%), insulin allergy (30%), lipodystrophy at the insulin injection sites (22%), and antinuclear antibodies (25%) in the patients. Alternation between hyperglycemia and hypoglycemia was observed in more than 90% of the patients. Most patients showed a high insulin autoantibody titer (>90%) and inappropriately increased insulin concentration (insulin/C-peptide molar ratio >7, >85%). We detected similar frequencies of DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 compared with previously reported frequencies in type 1 diabetes, and a lower frequency of DRB1*0406 compared with insulin autoimmune syndrome. The spontaneous remission rate exceeded 70%. Predisposing factors for autoimmune hypoglycemia caused by EIAS include a strong autoimmune background. Susceptible HLA genotypes for type 1 diabetes or insulin autoimmune syndrome might not explain susceptibility to this condition. Additionally, insulin autoantibodies and the insulin/C-peptide molar ratio are reliable screening options. The prognosis for this condition is favorable. Monitoring of insulin and insulin autoantibodies may contribute to treatment effectiveness.