Type 1 Diabetes Mellitus and Lipohypertrophy - Impact of the Intervention on Glycemic Control via Patient's Examination and Retraining on Change of Infusion Set.

OBJECTIVE: Lipohypertrophy (LH) is a common complication of insulin therapy in type 1 diabetes mellitus (T1DM). We examined whether an intervention consisting of LH assessment and retraining on insulin infusion set use improves glycemic control on subcutaneous insulin infusion (CSII) in patients with T1DM. METHODS: The intervention was conducted in 79 consecutive patients with T1DM. Data on glucose levels, glycated hemoglobin (HbA1c), and insulin doses were collected at baseline and after a median of 22 weeks (20-31.75 weeks). RESULTS: A total of 46 patients with T1DM (23 [50%] women) participating in the follow-up were characterized by a median age of 29 years (25-33.8 years), body mass index of 24.6 ± 3.3 kg/m2, T1DM duration of 16.5 years (8.3-20 years), and subcutaneous insulin infusion duration of 7 years (4-10.8 years). Patients' median HbA1c fell from 7.4% (6.7%-8.2%) to 7.05% (6.4%-7.6%) (P < .001), daily insulin dose/kg decreased (0.7 ± 0.20 vs 0.68 ± 0.15 IU/kg; P = .017) together with the total daily insulin dose (50.3 [40.5-62.7] vs 47.6 [39.8-62.1] IU; P = .019]. Furthermore, the percentage of basal insulin dose increased (43.0% [36-50] vs 44.0% [39.0-50.0]; P = .010], whereas the percentage of bolus dose decreased (57% [50-64] vs 56% [50-61], P = .010). CONCLUSIONS: The structured LH-related intervention in patients with T1DM on insulin pumps resulted in better glycemic control and a decrease in total daily insulin dose.

Evaluation of Lipohypertrophy in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injections or Continuous Subcutaneous Insulin Infusion.

OBJECTIVE: To determine lipohypertrophy (LH) in patients with type 1 diabetes mellitus (T1DM) on multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) and to reveal the factors associated with the development and severity of LH. METHODS: Sixty-six patients with T1DM treated with MDII (n = 35, 53%) or CSII (n = 31, 47%) for at least 1 year were included. LH localizations were detected with palpation and ultrasonography (USG). RESULTS: The LH detection rate with USG was significantly higher than that by palpation in the whole group (P < .001). The LH was detected with USG in 30 (85.7%) patients in the MDII group and 22 (71.0%) patients in the CSII group (P = .144). Advanced LH was detected in 13 (37.1%) of the patients treated with MDII and in 3 (9.7%) of the patients treated with CSII. LH was more severe in the MDII group than in the CSII group (P = .013). Diabetes duration and length of infusion set use were significantly longer and body mass index, hypoglycemia, and complication rates were higher in patients with LH than those in patients without LH (P < .05). A positive correlation was found between LH severity and HbA1C and insulin dose (P < .05, for both). MDII as insulin administration method, incorrect rotation, and a history of ketosis were found to be the most related factors with LH severity in a multiple linear regression analysis (P < .05). CONCLUSION: USG might be an effective approach for detecting and evaluating the severity of LH. MDII might cause more severe LH than CSII in patients with T1DM. In this study, LH was found to be associated mostly with incorrect rotation technique and a history of ketosis.

Lipohypertrophy and Insulin: An Old Dog That Needs New Tricks.

OBJECTIVE: To review the current status of practical knowledge related to insulin-associated lipohypertrophy (LH) - an accumulation of fatty subcutaneous nodules commonly caused by repeated injections and/or infusions of insulin into the same site. METHODS: Review of published literature with additional contributions from leading multidisciplinary experts with the emphasis on clinical aspects including pathophysiology, clinical and economic consequences, diagnosis, prevention and treatment. RESULTS: LH is the most common dermatologic complication of insulin therapy. Risk factors for the development of lipohypertrophy include repeated delivery of large amounts of insulin into the same location over time, repeated injection trauma to the skin and subcutaneous tissue, and multiple injections using the same needle. Subcutaneous insulin injection in skin areas with lipohypertrophy is associated with reduced pain; however, this problem can interfere with insulin absorption, thereby increasing the likelihood of glucose variability, hypo- and hyperglycemia when a site is changed. Modern visualization technology of the subcutaneous space with ultrasound can demonstrate lipohypertrophy early in the course of its development. CONCLUSIONS: The physiological and psychological consequences of developing insulin lipohypertrophy can be prevented and treated with education focusing on insulin injection techniques.

A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema.

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.

Prevalence of Lipohypertrophy and its Associations in Insulin-Treated Diabetic Patients.

Background and Objectives: Lipohypertrophy is a major complications of insulin therapy especially attributed to incorrect insulin technique. The objective was to determine the frequency of lipohypertrophy in diabetic population on insulin and its associations. Methods: This cross-sectional study was conducted at the Services Hospital Lahore from July 1st, 2020 to December 31st, 2020. Total of 363 diabetic patients, fulfilling the inclusion criteria were approached. The patients were examined and interviewed through a validated questionnaire. The data was stratified according to the age, gender, duration of diabetes, duration of insulin use, frequency of LH and duration since last instructions reviewed. The chi-square test was applied. Data was analyzed using SPSS 22. Results: Mean age of the study population was 49.71± 13.36 years. Majority were females (57.6%). LH was noted in 22.86% of participants (n=83). There was significant statistical difference noted (P <0.05) between different age groups as 29.7 % of patients in age group above 45 had LH as compared to 19.6% in the below 45 years age group. More females (28.2%) were having LH than the males (15.6%) with P<0.05. Also, significant difference was noted for needle reuse more than 10 times, more than two injections per day and longer duration since last instructions reviewed. No significant difference was noted between different devices for injection as well as for duration of diabetes. LH is strongly associated with hypoglycemia and hyperglycemia with P<0.05. Conclusion: A significant diabetic population on insulin has noted to have LH, and the risk is more with aged population, female gender, more injections per day and multiple time needle reuses. Risk of LH can be reduced by reinforcing education.

Lipohypertrophy Monitoring Study (LIMO): Effect of single use of 4 mm pen needles combined with education on injection site rotation on glycaemic control: Confirmation of an unpleasant truth.

AIMS: To investigate whether single use of 4 mm needles combined with education about injection technique and lipohypertrophy affects HbA1c, hypoglycaemia and glucose variability. METHODS: Insulin-injecting people with diabetes recruited from nine Belgian diabetes centres were prospectively followed for 6 months. They were provided 4 mm pen needles and education concerning injection technique using an online platform (BD and Me™) based on the international Forum for Injection Technique & Therapy Recommendations focused on avoidance of lipohypertrophy zones and reduction of needle reuse. RESULTS: A total of 171 people with diabetes were included of which 146 completed the study. At baseline, lipohypertrophy was present in 63.0% of those who completed the study, with 51.4% injecting in zones of lipohypertrophy, 37.0% incorrectly rotating and 95.9% reusing needles. After the intervention, 7.5% still injected in a lipohypertrophy zone, 4.1% rotated incorrectly and needle reuse decreased to 21.2%. The number of participants with severe hypoglycaemias (from 15.8% to 4.1%, p < 0.001), unexplained hypoglycaemias (from 46.6% to 16.4%, p < 0.001) and high glucose variability (from 64.4% to 29.5%, p < 0.001) was significantly reduced. HbA1c and total daily insulin dose remained stable. CONCLUSION: The combination of 4 mm pen needles and online education on injection techniques significantly reduced the number of people with severe hypoglycaemic episodes, unexplained hypoglycaemia and high glucose variability but did not improve HbA1c control nor lower insulin needs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04659330.

LIPODYSTROPHY FREQUENCY ACCORDING TO INSULIN TREATMENT REGIMEN IN TYPE 2 DIABETIC PATIENTS: IS INSULIN INJECTION FREQUENCY MATTERS IN ANALOG INSULIN ERA?

Objectives: We aimed to determine lipodystrophy frequency according to insulin treatment regimen and insulin injection frequency in type 2 diabetic patients. Methods: A total of 345 type 2 diabetic patients under insulin treatment for at least one year were included in this cross-sectional study. Patients were examined for presence of lipodystrophy, insulin injection frequency and dosage. Lipodystrophy was evaluated with visual inspection and palpation of all injection sites. Patients were evaluated into three categories according to daily insulin dose requirement: Group 1= Standard-dose insulin users 0.6 U/kg/day; Group 2= Medium-dose insulin users 0.61-1.9 U/kg/day, Group 3= High-dose insulin users ≥2 U/kg/day. Results: Lipodystrophy was seen in 28% of the patients. Lipodystrophy was significantly higher in group 3. There was no significant difference between the groups in terms of lipodystrophy size. Duration of insulin treatment, daily total insulin dose, daily insulin dose per weight and number of daily insulin injections were significantly higher in the group with lipodystrophy. Daily injection number of long-acting, rapidly-acting analog and total insulin injections were significantly higher in group 3 than group 1 and 2. Number of daily insulin injections and lipodystrophy frequency were significantly higher in basal-bolus insulin user group. Multivariate analysis showed that insulin injection frequency is the independent risk factor for lipodystrophy. Conclusion: Lipodystrophy is still a clinical problem in patients with high-dose insulin requirement and frequent insulin injections. Reducing daily insulin requirement and daily number of injections should be given priority in the management of patients to prevent the development of lipodystrophy.

Insulin Adverse Events.

The negative consequencies of diabetes treatment are traditionally regarded as caused by a disastrous treatment rather than adverse events of the insulin preparations. However, hypoglycemia, changes at the injection site (lipatrophy, lipoma), insulin allergy, obesity and increased risk of certain forms of cancer can easily be regarded as adverse events of the drug, and needle-phobia, psychological problems, increased risk of suicide are adverse events related to insulin and its administration. Also macroangiopathy and even microangiopathy to some extent can be regarded as adverse events as the most crucial part of the treatment of Type 1 diabetes is the insulin treatment. There is still room for improvments of insulin as a drug. We need insulins with more predictable absorption and kinetics, leading to more stable near-normal blood glucose, less risk of hypoglycemia, less effect in periphery and more effect on the liver, and less risk of vascular complications, obesity, cancer.

Lipodystrophy diagnosis in people living with HIV/AIDS: prediction and validation of sex-specific anthropometric models.

BACKGROUND: Body composition alterations, or lipodystrophy, can lead to serious health problems in people living with HIV/AIDS (PLWHA). The objectives of this study are to predict and validate sex-specific anthropometric predictive models for the diagnosis of lipodystrophy in PLWHA. METHODS: A cross-sectional design was employed to recruit 106 PLWHA (men = 65 and women = 41) in Brazil during 2013-2014. They were evaluated using dual-energy X-ray absorptiometry, and 19 regions of body perimeters and 6 skinfold thicknesses were taken. Sex-specific predictive models for lipodystrophy diagnosis were developed through stepwise linear regression analysis. Cross-validations using predicted residual error sum of squares was performed to validate each predictive model. RESULTS: Results support the use of anthropometry for the diagnosis of lipodystrophy in men and women living with HIV/AIDS. A high power of determination with a small degree of error was observed for lipodystrophy diagnosis for men in model six (r2 = 0.77, SEE = 0.14, r2PRESS = 0.73, SEE PRESS = 0.15), that included ratio of skinfold thickness of subscapular to medial calf, skinfold thickness of thigh, body circumference of waist, formal education years, time of diagnosis to HIV months, and type of combined antiretroviral therapy (cART) (with protease inhibitor "WI/PI = 1" or without protease inhibitor "WO/PI = 0"); and model five for women (r2 = 0.78, SEE = 0.11, r2PRESS = 0.71, SEE PRESS = 0.12), that included skinfold thickness of thigh, skinfold thickness of subscapular, time of exposure to cART months, body circumference of chest, and race (Asian) ("Yes" for Asian race = 1; "No" = 0). CONCLUSIONS: The proposed anthropometric models advance the field of public health by facilitating early diagnosis and better management of lipodystrophy, a serious adverse health effect experienced by PLWHA.

The association between insurance coverage for insulin pen needles and healthcare resource utilization among insulin-dependent patients with diabetes in China.

BACKGROUND: Pen needles are an important component of insulin delivery among patients with diabetes, but are not universally covered in China. We compared clinical and economic characteristics of insulin-dependent patients in China who have some level of pen needle (PN) reimbursement to those with no PN reimbursement. METHODS: A cross-sectional study was conducted among 400 insulin users with Type 1 or Type 2 diabetes treated in outpatient endocrinology units of four large tertiary care hospitals in Nanjing, Chongqing, Beijing and Zhengzhou. Demographics, medical history, healthcare resource utilization (RU), out-of-pocket costs, insurance and PN reimbursement status were surveyed. Unit costs were assigned to healthcare RU and compared using descriptive statistics and multivariate regression models. RESULTS: A total of 400 patients were analyzed; 142 (35.5%) with some level of PN coverage/reimbursement and 258 (64.5%) without. Patients without PN reimbursement had a higher prevalence of lipohypertrophy (59.3% vs. 40.7%, p = 0.0007), greater median PN reuse (12 vs. 7 times per needle, p < 0.0001), greater 6-month insulin costs (1591 vs. 1328 Renminbi [RMB], p = 0.0025) and total unadjusted 6-month expenditures (6433 vs. 4432 RMB, p < 0.0001), respectively. After controlling for clinical and demographic characteristics, patients without PN reimbursement had 4.6 times greater odds of high costs compared to those with PN reimbursement. CONCLUSIONS: Insulin users without PN reimbursement may pose a greater economic burden to China compared to those with PN reimbursement. Expansion of insurance coverage for insulin PNs can improve the quality of care and potentially help reduce the economic burden in this population.

Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection.

BACKGROUND: Obesity and lipohypertrophy are common in treated human immunodeficiency virus (HIV) infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral therapy (ART). METHODS: We present a consensus opinion on the diagnosis, clinical consequences, and treatment of excess adiposity in adults with treated HIV infection. RESULTS: Obesity and lipohypertrophy commonly occur among HIV-infected adults on ART and may have overlapping pathophysiologies and/or synergistic metabolic consequences. Traditional, HIV-specific, and ART-specific risk factors all contribute. The metabolic and inflammatory consequences of excess adiposity are critical drivers of non-AIDS events in this population. Although promising treatment strategies exist, further research is needed to better understand the pathophysiology and optimal treatment of obesity and lipohypertrophy in the modern ART era. CONCLUSIONS: Both generalized obesity and lipohypertrophy are prevalent among HIV-infected persons on ART. Aggressive diagnosis and management are key to the prevention and treatment of end-organ disease in this population and critical to the present and future health of HIV-infected persons.

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection.

PURPOSE OF REVIEW: The aim of this review is to summarize knowledge of the prevalence, relevant physiology, and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions. RECENT FINDINGS: Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist. Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

Ultrasound characterization of insulin induced lipohypertrophy in type 1 diabetes mellitus.

OBJECTIVE: Subcutaneous insulin absorption is one of the key factors affecting glycemic control in patients with diabetes mellitus under insulin therapy. Insulin-induced subcutaneous lipohypertrophy has been reported to impair insulin regular absorption and hence glycemic control. So far, lipohypertrophy diagnosis has only been clinical. This study aims at evaluating the possible role of ultrasound scan in the assessment of subcutaneous lipohypertrophy in patients affected by type 1 diabetes mellitus. METHODS: A pilot observational retrospective study was performed in 20 patients affected by type 1 diabetes mellitus. In these patients the areas with clinical evidence of lipohypertrophy dependent on the insulin injections were characterized by the presence of tissues that at the ultrasound scan resulted similar to fibrotic tissues (hyperechogenic) or to an interstitial edema or to fat tissues (hypoechogenic). It was utilized a multi frequency linear probe (6-18 MHz). The patients were advised to avoid insulin injections on the areas with lipohypertrophy scanned by the ultrasound and the HbA1c changes were evaluated 3 months later. RESULTS: The lipohypertrophic areas presented at least three different aspects upon ultrasound assessment: the iso-hyperechogenic one, with a predominant fibrotic component; the isoechogenic one, with "large tangles" fibrotic elements and the iso-hypoechogenic aspect with no fibrotic elements. When patients were advised to avoid insulin injections on areas with lipohypertrophy defined by ultrasound scan, 3 months after the first evaluation HbA1c had significantly improved (basal HbA1c 7.87 ± 0.56 versus 7.67 ± 0.52 3 months later, p = 0.029). No significant improvements of the HbA1c were found in the control matched group in which lipohypertrophy was only clinically valued through inspection and palpation. CONCLUSIONS: Ultrasound scan can help identify and characterize the lipohypertrophic areas and this might be useful to improve glycemic control.

Differences in depression, treatment satisfaction and injection behaviour in adults with type 1 diabetes and different degrees of lipohypertrophy.

AIMS AND OBJECTIVES: To assess the prevalence of lipohypertrophy, and to compare differences in external, personal and regimen factors in adults with type 1 diabetes and different degrees of lipohypertrophy. BACKGROUND: Suboptimal insulin injection behaviour is associated with lipohypertrophy, which may affect insulin absorption and lead to blood glucose fluctuations. Few, if any studies have investigated how external, personal and regimen factors differ in people with type 1 diabetes and different degrees of lipohypertrophy. DESIGN: A cross-sectional study including adults with type 1 diabetes at a diabetes outpatient clinic in a Norwegian university hospital. METHODS: Participants (n = 215) were included consecutively at scheduled appointments. Sociodemographic, diabetes and insulin treatment data, and self-report questionnaires concerning patient activation (Patient Activation Measure), depression (Patient Health Questionnaire-2), diabetes distress (Diabetes Distress Scale), type D personality (14-item Type D scale), treatment satisfaction (Insulin Treatment Satisfaction Questionnaire) and motivation (Treatment Self-Regulation Questionnaire), were collected. Lipohypertrophic injection sites were identified by palpation by diabetes specialist nurses. RESULTS: Lipohypertrophy was present in 53% and was more frequent in insulin pen users (63%) compared to insulin pump users (34%). Participants with two or more lipohypertrophic areas had higher depression scores, lower treatment satisfaction with glycaemic control, higher bolus doses and reported suboptimal injection behaviour compared to those with no lipohypertrophic areas. There were no differences in patient activation, diabetes distress, type D personality or motivation between the groups. DISCUSSION AND CONCLUSION: Compared to pump treatment, pen treatment requires greater awareness of injection technique. Symptoms of depression and lower treatment satisfaction might affect diabetes self-management and glycaemic control, but the association with lipohypertrophy needs further exploration. RELEVANCE TO CLINICAL PRACTICE: Lipohypertrophy is more frequent in insulin pen users compared to pump users. Nurses should focus on injection technique education, and should also consider screening for depressive symptoms and treatment satisfaction as these factors could be associated with development of lipohypertrophy.

Lipodystrophy among HIV-infected patients: a cross-sectional study on impact on quality of life and mental health disorders.

BACKGROUND: Lipodystrophy (LD) is a frequent adverse event of combination antiretroviral therapy (ART) and occurs mainly in patients exposed to first-generation antiretroviral drugs. The aim of this study was to explore and measure the interaction between LD, mental health, and quality of life of human immunodeficiency virus (HIV) positive individuals seen in a metabolic clinic. METHODS: We conducted a single-site cross-sectional study including all HIV-infected patients attending the LIPO group and metabolism day clinic at the University Hospitals of Geneva, Switzerland between January 31, 2008 and November 28, 2013. Data on LD were prospectively collected using the HIV Outpatient Study (HOPS) score, the Lipodystrophy Case Definition (LDCD), ART regimens, anthropometric measures, imaging, and standardized questionnaires. Quality of life was evaluated using a visual analog scale of 0-100. Depression and anxiety were assessed using the Beck Depression Inventory and the State Trait Anxiety Inventory scales, respectively. RESULTS: One hundred ninety-four patients (54.6% male; 45.4% female; median age, 50 years) on successful ART (median CD4 cell count, 569.0 cells/mm(3); median viral load, 20 copies/mL) were evaluated. Among these, 62.7, 63.5 and 35.5% of patients reported at least one body site affected by fat hypertrophy, atrophy or both, respectively. Using the LDCD score conservative definition, including imaging and biological values, 57.8% were diagnosed with LD. Of these, 39.7% suffered from severe/very severe LD. Depression was reported by 35.6% of individuals; 51.9% had anxiety symptoms and 49.5% reported poor quality of life (defined as being inferior to 50% on a scale from 0 to 100%). LD (odds ratio (OR = 5.22, 95% confidence interval (CI) 1.07-25.37, p-value: 0.040), depression (OR = 4.67, 95% CI 1.08-20.31, p-value 0.040), and anxiety (OR = 7.83, 95% CI 1.91-32.03, p-value 0.004) all affected significantly the quality of life. CONCLUSIONS: LD, depression and anxiety were frequent features among HIV-infected individuals seen in the metabolic clinic and significantly impacted on their quality of life.

Type 1 diabetes: Syndromes in resource-challenged settings.

Type 1 Diabetes is a complex disorder that is made more complex by the myriad of co-morbid conditions associated with it. Mauriac Syndrome is a well-known but nowadays uncommon condition that presents with growth retardation secondary to poor glycaemic control. Limited Joint Mobility is an often-missed association of diabetes. Its importance lies in the fact that it can cause significant impairment of fine movements in T1DM children. It also indicates poor glycaemic control over a long period of time and can be used as a surrogate marker for development of diabetic microvascular complications. Anaemia in T1DM is protean and can develop due to a combination of nutritional factors, chronic renal disease, coeliac disease and worm infestation. Management is etiological. Vitamin deficiencies are ubiquitous in T1DM and if left untreated, can lead to neurological, haematological and skeletal dysfunction. The best-known co-morbid conditions are the local site reactions clubbed together under the moniker lipodystrophies. These can be either atrophic or hypertrophic and are usually due to repeated injections at the same site, improper technique and needle re-use. Management is often difficult and they are best prevented by appropriate diabetes education and emphasis on proper injection techniques at the time of T1DM diagnosis, with periodic reinforcement. Amyloidosis is a little known condition that shares a lot of features in common with the lipodystrophies and often needs to be differentiated from lipohypertrophy. T1DM is a disease which is often associated with a poor quality of life and these co-morbid conditions also need to be treated for effective general and psychological well-being.

The development of simple anthropometric measures to diagnose antiretroviral therapy-associated lipodystrophy in resource limited settings.

BACKGROUND: Lipohypertrophy does not appear to be an adverse ART reaction while lipoatrophy is clearly associated with the use of stavudine (d4T) and zidovudine (AZT). In low and middle income countries d4T has only recently been phased out and AZT is still widely being used. Several case definitions have been developed to diagnose lipodystrophy, but none of them are generalizable to sub-Saharan Africa where black women have less visceral adipose tissue and more subcutaneous adipose tissue than white women. We aimed to develop a simple, objective measure to define lipoatrophy and lipohypertrophy by comparing patient report to anthropometric and dual-energy X-ray absorptiometry (DXA) -derived variables. METHODS: DXA and anthropometric measures were obtained in a cross sectional sample of black HIV-infected South African men (n = 116) and women (n = 434) on ART. Self-reported information on fat gain or fat loss was collected using a standard questionnaire. Receiver operating characteristic (ROC) curves were used to describe the performance of anthropometric and DXA-derived variables using patient reported lipoatrophy and lipohypertrophy as the reference standard. RESULTS: Lipoatrophy and lipohypertrophy were more common in women (25% and 33% respectively) than in men (10% and 13% respectively). There were insufficient numbers of men with DXA scans for meaningful analysis. The best predictors of lipoatrophy in women were the anthropometric variables tricep (AUC = 0.725) and thigh skinfold (AUC =0.720) thicknesses; and the DXA-derived variables percentage lower limb fat (AUC = 0.705) and percentage lower limb fat/height (AUC = 0.713). The best predictors of lipohypertrophy in women were the anthropometric variable waist/hip ratio (AUC = 0.645) and the DXA-derived variable percentage trunk fat/percentage limb fat (AUC = 0.647). CONCLUSIONS: We were able to develop simple, anthropometric measures for defining lipoatrophy and lipohypertrophy, using a sample of black HIV-infected South African women with DXA scans. This is of particular relevance in resource limited settings, where health professionals need simple and inexpensive methods of diagnosing patients with lipoatrophy and lipohypertrophy.

HIV and adipose tissue: A long history linked to therapeutic classes of antiretrovirals.

HIV infection has been controlled only since the introduction of triple therapy in 1996, combining, as antiretroviral agents, two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (PI). However, among the NRTIs, the thymidine analogues stavudine and zidovudine led to lipoatrophy, either generalized or associated with visceral fat hypertrophy and buffalo hump. These molecules also increased insulin resistance and the prevalence of diabetes. They were replaced by other NRTIs or non-NRTIs (NNRTIs) that were considered to be free of adipose tissue (AT) toxicity. More recently, the NRTI tenofovir disoproxyfumarate (TDF) and the NNRTI efavirenz have been associated with inhibition of fat gain but not with clear lipoatrophy. Otherwise, the use of PIs led to a phenotype of trunk fat hypertrophy associated with cardiometabolic complications. To avoid their adverse effects, PIs have recently been replaced by a new class of antiretrovirals, the integrase inhibitors (INSTIs), which are well tolerated and effective in controlling HIV. However, this class has been associated with global weight gain, which may be important and concerning for some people living with HIV (PWH). Also, in the NRTI class, TDF has often been replaced by tenofovir alafenamide (TAF) due to bone and renal toxicities, and TAF has been associated with global fat gain. The cardiometabolic consequences of INTIs and TAF are primarily related to the associated weight gain. In the global obesogenic worldwide context, PWH are gaining weight as well in relation to poor health life conditions. Taking in charge obesity uses the same strategies as those used in the general population.

Differences in clinicopathological characteristics between lipohypertrophy and localized insulin-derived amyloidosis: A scoping review.

Insulin is used as a therapeutic agent in patients with diabetes, and cutaneous lipohypertrophy (LH) and localized insulin-derived amyloidosis (LIDA) are well-known adverse effects associated with insulin injections. The clinical implications, management, assessment methods, and pathological differentiation of LH and LIDA have been recently updated. This review was to update our knowledge of the pathological differentiation, effects of insulin absorption, hypoglycemic events, and recent assessment methods for LH and LIDA. A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews guidelines. Original studies and case reports in English were also included. PubMed and Scopus databases were searched for keywords to identify papers published up to January 2022. A total of 113 studies were identified through a database search, and 31 were eligible for inclusion in this scoping review. In the 31 studies included in this review, patients with type 2 diabetes had high frequencies of LH and LIDA. LH outcome parameters were assessed using pathological findings and imaging. LIDA is mainly determined by pathological methods, such as hematoxylin and eosin and Congo red staining. Several in vitro and in vivo LIDA models of LIDA have been developed. These results suggest that pathological analysis is required to identify LH and LIDA. It is important to consider LIDA, as it likely influences insulin adsorption and glycemic control. Although several studies have evaluated the LIDA process, little is known about the mechanisms underlying the development of adverse effects associated with insulin injections.

Relationship Between Lipohypertrophy, Glycemic Control, and Insulin Dosing: A Systematic Meta-Analysis.

Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.