Search Results (12)

Over 100 years after its commercialization, the insulin administration method still needs elementary education. Such observation contrasts with technological progress constantly elaborating new (e.g., weekly) insulin preparations, capable of mimicking the pharmacokinetics of insulin produced by the human pancreas and exploring alternatives to injection. However, insulin administration remains anchored to the subcutaneous route, thus creating the conditions for lipohypertrophies (LHs), a still too frequent and ubiquitously widespread skin complication that, despite being avoidable with an adequate educational path, affects up to 60% of patients and even more. Considering that there are approximately 580 million adult diabetic people in the world today, at least half of whom (290 million) self-inject insulin, should 50% of the latter have LH, approximately 145 million people and even more? Considering that there are approximately 580 million adult diabetic people in the world today, at least half of whom (290 million) self-inject insulin, should 50% of the latter have LH, approximately 145 million people would suffer from such a complication, thus causing a severe problem for the global health system. Indeed, besides being unsightly, LHs cause poor glycemic control, large glucose variability, and frequent unexplained hypoglycemia, and display a strong correlation with micro- and macrovascular complications, inevitably worsening the quality of life of diabetic people. In this narrative review, after a brief description of the alternative routes of administration to subcutaneous injections, we will recall the causes, consequences, and possible corrective actions of LHs, stigmatizing the fundamental role of therapeutic education and hoping that all this can interest all the actors who revolve around the management of insulin therapy, which is too often underestimated and hastily addressed by health professionals, who probably prefer to dedicate time to titration of therapy. Ultimately, our aim is to provide the reader with a practical review of injection errors resulting from incorrect insulin injection techniques, analyzing the leading causes of error and the consequences of these errors, while also providing advice and suggestions to overcome all this. Full article

Introduction: The most frequent local complication of insulin injection is the occurrence of subcutaneous nodules due to incorrect injection technique. Injection into nodules negatively impacts metabolic compensation and the requirement for greater insulin doses due to its partial and erratic absorption. Despite these concepts being accepted by the scientific community, it is not yet clear whether injection into nodules is causally related to worsening chronic diabetes (DM) complications and the morphological nature of such nodules. Aim: This multicenter study aimed to evaluate the associations between structural characteristics of skin nodules and chronic DM complications. A secondary endpoint was to evaluate the histological structure of those nodules, looking for differences between lipohypertrophies (LH) and amyloid nodules (LIDA). Methods: For this purpose, 816 DM patients with LH and 1033 without LH underwent a clinical and ultrasound study comparing metabolic data, injection habits, and frequency of complications. Excisional biopsies of the skin nodules were performed in a small series of eight subjects. Results: Data observed confirm a strong relationship between LH and diabetes chronic complications other than poor glycemic control. Histology of biopsies from the skin nodules showed mild foreign-body-like inflammation, prevailing mega-adipocytes (65%), apoptosis, and fibrosis but could not detect any amyloid fibrils. In four cases, intra-nodular fluid was present with an insulin concentration several times higher than in blood. Conclusions: We confirmed LHs to be significantly associated with insulin administration errors, duration of insulin therapy, greater daily doses and duration of insulin administration, and the presence of micro- and macro-vascular DM complications. LH nodules displayed no typical morphological features and were indistinguishable from LIDA nodules with which they shared several histologic similarities, albeit within the frame of a general picture of LIDA inhomogeneity. Further targeted studies are warranted to clarify the remaining doubts. Full article

Localized insulin-derived amyloidosis (LIDA) is a rare local complication of subcutaneous insulin application occurring in patients with diabetes type 1 and 2. A 45-year-old woman with an 11-year history of insulin-dependent diabetes mellitus type 1 underwent a mini-abdominoplasty and excision of a long-standing palpable mass in left hypogastric subcutaneous tissue in the area of long-term insulin application. Histopathological examination revealed insulin amyloidosis as a substrate of the mass lesion. Several months after surgery, there was a transient improvement in previously poor diabetes compensation. In addition to local allergic reactions, abscess formation, scarring, lipoatrophy/dystrophy, and lipohypertrophy, LIDA broadens the differential diagnostic spectrum of local insulin injection complications. LIDA has been described as a cause of poor glycemia compensation, probably due to the conversion of soluble insulin into insoluble amyloid fibrils, which prevents insulin from circulating in the blood and regulating glucose blood concentration. Improvement in diabetes compensation has been described in several reports, including our case. LIDA is a rare local complication of subcutaneous insulin application; accurate diagnosis and treatment have clinical consequences. Immunohistochemical or immunofluorescence distinction from other amyloid types is highly recommended. Full article

Aims: 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. Methods: 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 (HbA_1C) and other glycemic-related indicators. Results: 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 HbA_1C 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). Conclusions: 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. Full article

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses. Full article

The causes and metabolic consequences of lipohypertrophy (LH) from incorrect insulin injection techniques have been well-known for a long time and are the subject of countless publications. However, only some researchers propose structured research modalities for LH and programs to teach patients how to prevent them and minimize their effects, thus contributing to complete rehabilitation. Experts and scientific societies have produced consensus documents and recommendations to spread the culture of LH and its complications among clinicians. However, they should go deeper into LH detection methods. This short article analyzes the recent literature on the best way to explore and find more or less evident LH lesions by using a structured and validated clinical methodology to benefit the many clinicians without access to technological equipment such as ultrasonography. This text also aims to bring awareness that since the last published recommendations on injection techniques, new needles for insulin injection, more technologically advanced and suitable for specific populations, have come to market but still need a thorough evaluation. Full article

The use of the transdermal delivery system has recently gained ample recognition due to the ability to deliver drug molecules across the skin membrane, serving as an alternative to conventional oral or injectable routes. Subcutaneous insulin injection is the mainstay treatment for diabetes mellitus which often leads to non-compliance among patients, especially in younger patients. Apart from its invasiveness, the long-term consequences of insulin injection cause the development of physical trauma, which includes lipohypertrophy at the site of administration, scarring, infection, and sometimes nerve damage. Hence, there is a quest for a better alternative to drug delivery that is non-invasive and easily adaptable. One of the potential solutions is the transdermal delivery method. However, the stratum corneum (the top layer of skin) is the greatest barrier in transporting large molecules like insulin. Therefore, various chemical enhancers have been proposed to promote stratum corneum permeability, or they are designed to increase the permeability of the full epidermis, such as the use of ionic liquid, peptides, chemical pre-treatment as well as packaging insulin with carriers or nanoparticles. In this review, the recent progress in the development of chemical enhancers for transdermal insulin delivery is discussed along with the possible mechanistic of action and the potential outlook on the proposed permeation approaches in comparison to other therapeutical drugs Full article

Multiple daily injections via subcutaneous route are the primary modes of insulin delivery for patients with Diabetes Mellitus. While this process is invasive, painful and may cause patients to develop lipohypertrophy at injection site, the perception of fear surrounding this process causes patients to delay in initiation and remain persistent with insulin therapy over time. Moreover, poor glycemic control may often lead to acute complications, such as severe hypoglycemia and nocturnal hypoglycemia, especially in older patients with diabetes. To address the imperative need for a patient-convenient non-invasive insulin therapy, an insulin-loaded arginine-coated self-emulsifying nanoglobule system (INS-LANano) was developed for nasal delivery of insulin with a biodegradable cationic surfactant—Lauroyl Ethyl Arginate (LAE). Incorporation of LAE resulted in formation of positively charged nanoglobules with L-arginine oriented on the surface. LANano enabled binding of insulin molecules on the surface of nanoglobules via an electrostatic interaction between negatively charged α-helix and LAE molecules at physiological pH. INS-LANano showed a hydrodynamic diameter of 23.38 nm with a surface charge of +0.118 mV. The binding efficiency of insulin on LANano globules was confirmed by zeta potential, circular dichroism (CD) spectroscopy and centrifugal ultrafiltration studies. The attachment of insulin with permeation-enhancing nanoglobules demonstrated significantly higher in vitro permeability of insulin of 15.2% compared to insulin solution across human airway epithelial cell (Calu-3) monolayer. Upon intranasal administration of INS-LANano to diabetic rats at 2 IU/kg insulin dose, a rapid absorption of insulin with significantly higher Cmax of 14.3 mU/L and relative bioavailability (BA) of 23.3% was observed. Therefore, the INS-LANano formulation significant translational potential for intranasal delivery of insulin Full article

The number of adult individuals with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. The main local complications of insulin injection are lipohypertrophies (LHs), i.e., subcutaneous nodules consisting of aggregates of macro-adipocytes and fibrin. These nodules result from errors repeatedly made by patients while injecting insulin. Despite being very common, LH lesions/nodules due to incorrect insulin injection techniques are often flat and hardly visible and thus require thorough deep palpation examination and ultrasonography (US) for detection. Identifying LHs is crucial, especially in elderly and frail subjects, because they may eventually result in poor diabetes control due to associated unpredictable insulin release patterns. Raising awareness of the adequate detection of LHs and their clinical consequences is crucial and urgent. A call to action is required on this topic at all levels of undergraduate and postgraduate education. Full article

Lipodystrophy is the most common dermatological complication in patients with diabetes on insulin therapy. Despite the high frequency of lipodystrophy, there are still several difficulties in giving advice about avoidance into practice among children and adolescents with type 1 diabetes and their caregivers. This cross-sectional study aims to evaluate the prevalence of insulin-induced lipodystrophy in a cohort of pediatric patients with type 1 diabetes, to identify associated clinical factors and to assess its influence on glycemic control. Two hundred and twelve patients attending our Diabetes Center during a three-month period were enrolled. The presence of lipodystrophy was assessed by inspection and palpation procedures. Demographic and clinical data including type of treatment, frequency of rotation of insulin administration sites, and glucose metrics of the previous 30 days were assessed and statistically analyzed. Prevalence of lipohypertrophy was 44.3%. Two patients were affected by lipoatrophy (0.9%). Improper rotation of insulin administration sites and low awareness on lipodystrophy were associated to the occurrence of this skin condition (p = 0.050 and p = 0.005, respectively). When comparing patients with and without lipodystrophy, a significant difference in glycemic variability parameters was detected (p = 0.036 for coefficient of variation, p = 0.029 for standard deviation score of glucose levels). Lipodystrophy still represents a common complication in patients on insulin therapy. The present study reveals its negative impact on glycemic variability. This finding emphasizes the importance of prevention strategies to minimize the occurrence of this dermatological complication that may interfere with clinical history of the disease. Full article

Diabetes is a common and complex disease affecting multiple organ systems throughout the body. With a consensus in care guidelines emphasizing the importance of glycemic control in determining the disease progression, people with diabetes worldwide have been placed on medication regimens targeting glucose stability from a variety of pathophysiologic pathways. Each of these medications also possesses its own potential for adverse events. In recent years, there has been increased reports of skin reactions to diabetes medications, adding to the more widely known eruptions such as insulin-induced lipohypertrophy and contact dermatitis of subcutaneous injections. The authors searched PubMed, Google, and Embase for articles including adverse reactions to anti-hyperglycemic medications. Key words and titles searched included, “antidiabetic drugs”, “skin reactions”, “adverse drug reactions”, “allergic reactions”, “diabetes”, “metformin”, “insulin”, “DPP4 inhibitors”, “thiazolindineones”, “sulfonylureas”, “SGLT2 inhibitors”, “GLP-1 agonists”, “diabetic medication”, “injection site reactions”. As a result, a total of 59 papers are included in this review. The great majority were case reports ranging from benign fixed drug eruptions to severe cutaneous reactions that threaten patients’ lives. Increasing physician awareness of both the potential for, and presentation of, such reactions to diabetes medications can reduce hospitalizations and optimize care in an already vulnerable patient population. Full article

Since the advent of HIV antiretroviral therapies at the end of the 20th century, the morbidity and mortality rates associated with HIV infection have decreased dramatically. Unfortunately, these benefits are associated with substantial morphologic changes in the body, such as abnormal fat distribution with peripheral lipohypertrophy and facial lipoatrophy. Facial wasting is considered the major stigma for HIV–infected people and may result in reduced antiretroviral adherence. Patients suffering from the stigmata of HIV infection can benefit from non-surgical aesthetic treatments performed with fillers or lipolytic agents that provide a quick and reliable service for facial rejuvenation, with high patient satisfaction and a low risk of complications. In the present paper, a retrospective analysis of complications following non-surgical aesthetic treatments (calcium hydroxyapatite-based filler, hyaluronic acid filler, polyacrylamide hydrogel filler and dehoxycholic acid injections), in a cohort of 116 consecutive HIV+ patients, treated over a period of 12 years, was performed. With the exception of the tardive swelling reported after calcium hydroxyapatite injections, complications were recorded just after polyacrylamide hydrogel treatment as small, palpable, nonvisible nodules or aseptic abscess. Our experience is consistent with those already published in the literature and the complication rate seems to be comparable to non-infected patients. Full article