Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa.

BACKGROUND: Congenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment. METHODS: CGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records. RESULTS: Data from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth-37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age. CONCLUSIONS: This analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.

Protease inhibitors (PIs) are associated with an incidence of lipodystrophy among people living with HIV(PLHIV). Lipodystrophiesare characterised by the loss of adipose tissue. Evidence suggests that a patient's lipodystrophy phenotype is influenced by genetic mutation, age, gender, and environmental and genetic factors, such as single-nucleotide variants (SNVs). Pathogenic variants are considered to cause a more significant loss of adipose tissue compared to non-pathogenic. Lipid metabolising enzymes and transporter genes have a role in regulating lipoprotein metabolism and have been associated with lipodystrophy in HIV-infected patients (LDHIV). The long-term effect of the lipodystrophy syndrome is related to cardiovascular diseases (CVDs). Hence, we determined the SNVs of lipid metabolising enzymes and transporter genes in a total of 48 patient samples, of which 24 were with and 24 were without HIV-associated lipodystrophy (HIVLD) using next-generation sequencing. A panel of lipid metabolism, transport and elimination genes were sequenced. Three novel heterozygous non-synonymous variants at exon 8 (c.C1400A:p.S467Y, c.G1385A:p.G462E, and c.T1339C:p.S447P) in the ABCB6 gene were identified in patients with lipodystrophy. One homozygous non-synonymous SNV (exon5:c.T358C:p.S120P) in the GRN gene was identified in patients with lipodystrophy. One novelstop-gain SNV (exon5:c.C373T:p.Q125X) was found in the GRN gene among patients without lipodystrophy. Patients without lipodystrophy had one homozygous non-synonymous SNV (exon9:c.G1462T:p.G488C) in the ABCB6 gene. Our findings suggest that novel heterozygous non-synonymous variants in the ABCB6 gene may contribute to defective protein production, potentially intensifying the severity of lipodystrophy. Additionally, identifying a stop-gain SNV in the GRN gene among patients without lipodystrophy implies a potential role in the development of HIVLD.

Familial Screening for the Prevention of Rare Diseases: A Focus on Lipodystrophy in Southern Saudi Arabia.

BACKGROUND: Lipodystrophy is a relatively rare, complex disease characterised by a deficiency of adipose tissue and can present as either generalised lipodystrophy (GLD) or partial lipodystrophy (PLD). The prevalence of this disease varies by region. This study aimed to identify the genetic variations associated with lipodystrophy in the southern part of Saudi Arabia. METHODOLOGY:  We conducted a retrospective study by recruiting nine patients from six families, recruiting the proband whole exome sequencing results or any other genetic test results, screening other family members using Sanger sequencing and analysing the carrier status of the latter. These patients were recruited from the Endocrinology and Diabetes Clinic at Jazan General Hospital and East Jeddah Hospital, both in the Kingdom of Saudi Arabia. RESULT: Eight patients were diagnosed with GLD, and one was diagnosed with PLD. Of the six families, four were consanguineously married from the same tribe, while the remaining belonged to the same clan. The majority of GLD patients had an AGPAT2 c.158del mutation, but some had a BSCL2 c.942dup mutation. The single PLD case had a PPARG c.1024C > T mutation but no family history of the disease. In all families evaluated in this study, some family members were confirmed to be carriers of the mutation observed in the corresponding patient. CONCLUSION:  Familial screening of relatives of patients with rare, autosomal recessive diseases, such as lipodystrophy, especially when there is a family history, allows the implementation of measures to prevent the onset or reduced severity of disease and reduces the chances of the pathogenic allele being passed onto future generations. Creating a national registry of patients with genetic diseases and carriers of familial pathogenic alleles will allow the assessment of preventive measures and accelerate disease intervention via gene therapy.

Clinical Characteristics of Patients With Acquired Partial Lipodystrophy: A Multicenter Retrospective Study.

BACKGROUND: Barraquer-Simons syndrome (BSS) is a rare, acquired form of lipodystrophy characterized by progressive loss of upper body subcutaneous fat, which affects face, upper limbs, and trunk. The pathogenesis of the disease is not entirely known and may involve autoimmune mechanisms. AIM: This study aimed to provide a comprehensive picture of the clinical, immunological, and metabolic features of a large cohort of patients with BSS. Our primary objectives included the validation of existing diagnostic tools, the evaluation of novel diagnostic approaches, and the exploration of potential disease triggers or genetic predispositions. SUBJECTS AND METHODS: Twenty-six patients were diagnosed with BSS based on accepted criteria defined by international guidelines. Anthropometric parameters, biochemical tests, organ- and non-organ-specific autoantibodies, HLA status, and screening of the LMNB2 gene were performed. RESULTS: Patients were predominantly females (73%); fat loss occurred mostly during childhood (77%) at a median age of 8 years. Among various anthropometric measures, the ratio between the proportion of fat mass in upper limbs and lower limbs showed the best predictive value for diagnosis. A total of 11.5% of patients had diabetes, 34.6% dyslipidemia, and 26.9% hepatic steatosis. Seventy-five percent of children and 50% of adults had C3 hypocomplementemia; 76% of patients were positive for 1 or more autoantibodies. HLA-DRB1 11:03 had higher allelic frequencies compared with the general population. A single variant in the LMNB2 gene was found in 1 patient. CONCLUSION: BSS has a childhood onset and is often associated with autoimmune diseases. Skinfold thickness measurements and fat assessment by dual energy X-ray absorptiometry are useful tools to identify the disease. C3 hypocomplementemia and the presence of autoantibodies may be used as additional diagnostic supportive criteria but the prevalence of C3 hypocomplementemia may be lower than previously reported.

Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review.

CONTEXT: Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss. OBJECTIVE: We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships. METHODS: We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature. RESULTS: The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not. CONCLUSION: This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases.

Prevalence and risk factors of metabolic syndrome in Ethiopia: describing an emerging outbreak in HIV clinics of the sub-Saharan Africa - a cross-sectional study.

OBJECTIVES: HIV-induced chronic inflammation, immune activation and combination antiretroviral therapy (cART) are linked with adverse metabolic changes known to cause cardiovascular adversities. This study evaluates the prevalence of lipodystrophy, and metabolic syndrome (MetS), and analyses risk factors in HIV-infected Ethiopians taking cART. METHODS: A multicentre cross-sectional study was conducted at tertiary-level hospitals. Eligible participants attending the HIV clinics were enrolled. Sociodemographic, anthropometric, clinical, HIV treatment variables, lipid profile, fasting blood glucose level, risk factors and components of MetS, also lipodystrophy, were studied. Data were analysed by SPSS statistical package V.25 with descriptive and analytical statistics. For multivariable analysis of risk factors, a logistic regression model was used. Results were presented in frequency and percentages, mean±SD, or median+IQR. Statistical significance was taken as p<0.05. RESULTS: Among 518 studied participants, two-thirds were females, and the mean age of the study population was 45 years (SD=11). The mean duration of cART was 10 years (SD=4). Median CD4 count was 460 cells/mm3. The prevalence of MetS according to the Adult Treatment Panel III (2005) criteria was 37.6%. In multivariable analysis, independent risk factors for MetS were age >45 years (aHR 1.8, 95% CI 1.2 to 2.4), female sex (aHR 1.8, 95% CI 1.1 to 2.8), body mass index (BMI)>25 kg/m2 (aHR 2.7, 95% CI 1.8 to 4.1), efavirenz-based cART (aHR 2.8, 95% CI 1.6 to 4.8) and lopinavir/ritonavir-based cART (aHR 3.7, 95% CI 1.0 to 13.3). The prevalence of lipodystrophy was 23.6%. Prior exposure to a stavudine-containing regimen was independently associated with lipodystrophy (aHR 3.1, 95% CI 1.6 to 6.1). CONCLUSION: Our study revealed 38% of the participants had MetS indicating considerable cardiovascular disease (CVD) risks. Independent risk factors for MetS were BMI≥25 kg/m2, efavirenz and lopinavir/ritonavir-based cART, female sex and age ≥45 years. In addition to prevention, CVD risk stratification and management will reduce morbidity and mortality in people with HIV infection.

Natural history and comorbidities of generalised and partial lipodystrophy syndromes in Spain.

The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.

Lipoatrofia semicircular en trabajadores de oficinas: una situación que no desaparece tan rápidamente / Semicircular lipoatrophy in public office workers. A situation that does not disappear so quickly

Introducción: La lipoatrofia semicircular (LS) es un trastorno caracterizado por depresiones en forma de banda en la cara anterolateral de los muslos. Objetivos: determinar la prevalencia de los casos de LS en varias instituciones públicas y privadas de la Provincia de Barcelona, España. Material y Métodos: se realizó estudio retrospectivo, en 969 trabajadores de oficinas públicas y privadas, entre 2018 y 2022. A todos los casos se les realizó examen físico completo con mediciones, fotografía y seguimiento de las lesiones. Los resultados fueron analizados mediante el programa Instat Graphpad 3.10 y se aplicó la prueba de Fischer para determinar la significancia estadística. Resultados: se diagnosticaron 96 casos de los cuales 92 eran mujeres. Prevalencia: 9,9%. El promedio de edad fue 49 años (27-64). La mayoría de las lesiones se localizaron en los muslos en forma bilateral. Las lesiones de LS al final del estudio no desaparecieron en el 60% de los casos, mientras que en un 40% si lo hicieron. Conclusiones: Las lesiones de LS toman un tiempo muy variable para revertir, suele ser un proceso lento cuya duración se mide habitualmente en años. Ni el teletrabajo, ni el índice de masa corporal, tuvieron relación estadísticamente significativa en la desaparición de las lesiones. (AU)

Introduction: Semicircular lipoatrophy (LS) is a disorder characterized by band-shaped depressions on the anterolateral aspect of the thighs. Objectives: to determine the prevalence of LS cases in various public and private institutions in the Province of Barcelona, Spain. Material and Methods: a retrospective study was carried out on 969 workers from public and private offices, between 2018 and 2022. All cases underwent a complete physical examination with measurements, photography, and follow-up of injuries. The results were analyzed using the Instat Graphpad 3.10 program and the Fischer test was applied to determine statistical significance. Results: 96 cases were diagnosed, of which 92 were women. Prevalence: 9.9%. The average age was 49 years (27-64). Most of the lesions were located on the thighs bilaterally. LS lesions at the end of the study did not disappear in 60% of cases, while in 40% they did. Conclusions: LS lesions take a highly variable time to reverse, it is usually a slow process whose duration is usually measured in years. Neither teleworking nor the body mass index had a statistically significant relationship in the disappearance of the lesions (AU)

Insulin-induced lipodystrophy and predisposing factors in children and adolescents with type 1 diabetes mellitus (T1DM) in a tertiary care Egyptian center.

BACKGROUND: Lipodystrophy (LH) is one of the most common complications of subcutaneous insulin injection. Many factors are incriminated in the evolution of LH in children with diabetes type 1 (T1DM). LH may affect insulin absorption in the skin areas involved, resulting in a negative impact on blood glucose levels and glycemic variability. PATIENTS AND METHODS: We calculated and evaluated the prevalence of LH in relation to possible clinical factors associated with the development of LH in a cohort of children (n =115) with T1DM using insulin pens or syringes and we studied possible predisposing factors including their age, duration of T1DM, injection technique, insulin dose/kg, degree of pain perception, and HbA1c level. RESULTS: In our cross-sectional study, 84% of patients were using pens for insulin injection and 52.2 % of them were rotating the site of injection on daily basis. 27 % did not experience pain during an injection while 6 % had the worst hurt. 49.5 % had clinically detectable LH. Those with LH had higher HbA1c levels and more unexplained hypoglycemic events compared to those without LH (P: 0.058). The hypertrophied site was related to the preferred site of injection which was the arms in 71.9 % of the cases. Children who had LH were older with a longer duration of T1DM, rotating sites of injection less frequently, and were more frequently reusing needles compared to children without LH (P: < 0.05). CONCLUSION: Improper insulin injection technique, older age, and longer duration of T1DM were associated with LH. Proper education of patients and their parents must include correct injection techniques, rotating injection sites, and minimal reuse of needles.

Lipoatrofia semicircular: estudio y seguimiento clínico de 76 casos en Madrid, España. Propuesta de clasificación / Lipoatrophia semicircularis: Clinical study and follow-up of 76 cases in Madrid, Spain. Classification proposal

Introducción: La lipoatrofia semicircular (LS) puede tener presentaciones clínicas variadas, sin criterios diagnósticos claros. Se han propuesto varios factores etiopatogénicos, incluyendo determinados ambientes laborales. En este manuscrito se pretende describir las características de un brote de casos sospechosos de LS que se inició en mayo de 2008 entre trabajadores del Ayuntamiento de Madrid. Con base en la experiencia acumulada, se describen las acciones realizadas por el Servicio de Salud Laboral y se proponen unos criterios clínicos con implicación pronóstica que permitan categorizar los casos. Material y método: Estudio observacional retrospectivo tipo serie de casos que incluye datos recogidos de forma prospectiva de los pacientes revisados en el Servicio de ITS/Dermatología del Ayuntamiento Madrid entre 2008 y 2021. Se lleva a cabo la descripción de las medidas realizadas desde Salud Laboral. A través del registro y análisis estadístico de las variables recogidas durante la evaluación clínica de los pacientes, se proponen unos patrones clínicos definidos. Resultados: Se estudiaron 75 mujeres y un hombre, seguidas en su mayoría durante un período con mediana de 37 meses. Los síntomas locales fueron poco frecuentes (14,5%). Se propone la clasificación de las pacientes en 4 grupos: LS típica, LS unilateral, lipoatrofia en banda en miembros inferiores y lipoatrofia inespecífica. Al comparar los 2 primeros grupos con los 2 últimos, pudo constatarse una evolución clínica más favorable (76 versus 25,8% de mejoría total o parcial de las lesiones), además de una asociación negativa con la presencia de hipertrofia del tejido subcutáneo (p<0,001). Discusión: La LS típica (que puede ser frecuentemente unilateral) tiene por lo general una evolución favorable y unas características definidas que permiten diferenciarla de otros cuadros de lipoatrofia. Las medidas descritas realizadas por el Servicio de Salud Laboral contribuyeron a dicha evolución (AU)

Introduction: The clinical presentations of Lipoatrophia semicircularis (LS) vary, and diagnostic criteria are unclear. Several etiopathogenic factors, including occupational environmental ones, have been suggested. We aimed to describe a cluster of cases of suspected LS that started to appear in May 2008 among employees of the city council of Madrid, Spain. We report the actions taken by the council's Occupational Health Service and propose clinical categories with prognostic implications. Material and method: Retrospective observational case series study including prospectively collected data from patients evaluated between 2008 and 2021 at the Madrid City Council STI/Dermatology Department. Information on measures taken by the Occupational Health Service is detailed. The recording of clinical variables for statistical analysis and the proposal of defined clinical patterns were carried out. Results: We studied the cases of 75 women and one man, most of whom attended follow-up visits for a median of 37 months. Local symptoms were observed in just 14.5% of patients. The cases were classified into 4 groups: typical LS, unilateral LS, band-like lipoatrophy in the lower limbs, and nonspecific LS. Clinical outcomes were more often favorable in the first 2 groups, in which 76% of patients achieved total or partial improvement of lesions (vs. 25.8% in the last 2 groups). LS was negatively associated with the presence of hypertrophic subcutaneous adipose tissue (P<.001). Discussion: Typical LS, which can often be unilateral, generally has a satisfactory outcome. The clinical characteristics of this form distinguish it from other types of lipoatrophy. Measures taken by the Occupational Health Service contributed to favorable outcomes. In this series, LS was not associated with marked subcutaneous adipose tissue hypertrophy in the thighs (AU)

[Translated article] Lipoatrophia semicircularis: Clinical study and follow-up of 76 cases in Madrid, Spain. Classification proposal / Lipoatrofia semicircular: estudio y seguimiento clínico de 76 casos en Madrid, España. Propuesta de clasificación

Introducción: La lipoatrofia semicircular (LS) puede tener presentaciones clínicas variadas, sin criterios diagnósticos claros. Se han propuesto varios factores etiopatogénicos, incluyendo determinados ambientes laborales. En este manuscrito se pretende describir las características de un brote de casos sospechosos de LS que se inició en mayo de 2008 entre trabajadores del Ayuntamiento de Madrid. Con base en la experiencia acumulada, se describen las acciones realizadas por el Servicio de Salud Laboral y se proponen unos criterios clínicos con implicación pronóstica que permitan categorizar los casos. Material y método: Estudio observacional retrospectivo tipo serie de casos que incluye datos recogidos de forma prospectiva de los pacientes revisados en el Servicio de ITS/Dermatología del Ayuntamiento Madrid entre 2008 y 2021. Se lleva a cabo la descripción de las medidas realizadas desde Salud Laboral. A través del registro y análisis estadístico de las variables recogidas durante la evaluación clínica de los pacientes, se proponen unos patrones clínicos definidos. Resultados: Se estudiaron 75 mujeres y un hombre, seguidas en su mayoría durante un período con mediana de 37 meses. Los síntomas locales fueron poco frecuentes (14,5%). Se propone la clasificación de las pacientes en 4 grupos: LS típica, LS unilateral, lipoatrofia en banda en miembros inferiores y lipoatrofia inespecífica. Al comparar los 2 primeros grupos con los 2 últimos, pudo constatarse una evolución clínica más favorable (76 versus 25,8% de mejoría total o parcial de las lesiones), además de una asociación negativa con la presencia de hipertrofia del tejido subcutáneo (p<0,001). Discusión: La LS típica (que puede ser frecuentemente unilateral) tiene por lo general una evolución favorable y unas características definidas que permiten diferenciarla de otros cuadros de lipoatrofia. Las medidas descritas realizadas por el Servicio de Salud Laboral contribuyeron a dicha evolución (AU)

Introduction: The clinical presentations of Lipoatrophia semicircularis (LS) vary, and diagnostic criteria are unclear. Several etiopathogenic factors, including occupational environmental ones, have been suggested. We aimed to describe a cluster of cases of suspected LS that started to appear in May 2008 among employees of the city council of Madrid, Spain. We report the actions taken by the council's Occupational Health Service and propose clinical categories with prognostic implications. Material and method: Retrospective observational case series study including prospectively collected data from patients evaluated between 2008 and 2021 at the Madrid City Council STI/Dermatology Department. Information on measures taken by the Occupational Health Service is detailed. The recording of clinical variables for statistical analysis and the proposal of defined clinical patterns were carried out. Results: We studied the cases of 75 women and one man, most of whom attended follow-up visits for a median of 37 months. Local symptoms were observed in just 14.5% of patients. The cases were classified into 4 groups: typical LS, unilateral LS, band-like lipoatrophy in the lower limbs, and nonspecific LS. Clinical outcomes were more often favorable in the first 2 groups, in which 76% of patients achieved total or partial improvement of lesions (vs. 25.8% in the last 2 groups). LS was negatively associated with the presence of hypertrophic subcutaneous adipose tissue (P<.001). Discussion: Typical LS, which can often be unilateral, generally has a satisfactory outcome. The clinical characteristics of this form distinguish it from other types of lipoatrophy. Measures taken by the Occupational Health Service contributed to favorable outcomes. In this series, LS was not associated with marked subcutaneous adipose tissue hypertrophy in the thighs (AU)

Advances in the care of lipodystrophies.

PURPOSE OF REVIEW: Lipodystrophies are a group of rare, heterogeneous disorders characterized by a lack or maldistribution of adipose tissue. Treatment focusses on the management of complications, including hypertriglyceridemia, which can be severe. Patients are predisposed to early atherosclerotic cardiovascular disease and acute pancreatitis. This review summarizes the recent advances in the treatment of lipodystrophies, with a particular focus on the treatment of hypertriglyceridemia in familial partial lipodystrophy (FPLD). RECENT FINDINGS: Treatment of dyslipidemia in FPLD requires management of secondary exacerbating factors, particularly insulin resistance and diabetes, together with modification of atherosclerotic cardiovascular disease risk factors. In addition, specific lipid-lowering therapies are usually needed, starting with statins and fibrates. Leptin therapy improves triglycerides. Several emerging treatments for hypertriglyceridemia include apo C-III antagonists (volanesorsen, AKCEA-APOCIII-LRx and ARO-APOC3) and angiopoietin-like 3 antagonists (evinacumab, vupanorsen and ARO-ANG3); efficacy observed in clinical trials of these agents in nonlipodystrophic patients with severe hypertriglyceridemia suggests that they may also be helpful in lipodystrophy. SUMMARY: Emerging therapies for dyslipidemia show promise in advancing the care of patients with lipodystrophy. However, these treatments are not yet approved for use in lipodystrophy. Further study of their efficacy and safety in this patient population is needed.

Hundred-year experience with insulin and lipohypertrophy: An unresolved issue.

In the article recently published in Diab Res Clin Pract (1), we described one of the most exciting paths in the history of medicine from the perspective of diabetologists and people with type 1 diabetes. Such a history lasted 100 years, from the discovery of insulin to the most technologically advanced technologies aimed at making treatment as close to physiology and user-friendly as possible. Indeed, we are luckier than others because, by living in Italy and the USA, respectively, we have access to miniaturized and computerized insulin delivery systems, but this is not the case worldwide. Due to that, while receiving many favorable comments from colleagues and friends, we were encouraged to further expand on the issue and go deeper into insulin injection technique.

Associations of insulin-induced lipodystrophy in children, adolescents, and young adults with type 1 diabetes mellitus using recombinant human insulin: a cross-sectional study.

OBJECTIVE: Insulin-induced lipodystrophy is of two types, lipohypertrophy and lipoatrophy. Lipodystrophy often leads to worsening of glycemic control in type 1 diabetes mellitus. Our objective was to identify the clinical, immunological, and other factor(s) associated with the development of lipodystrophy. METHODS: In this observational cross-sectional hospital-based study, 95 children, adolescents, and young adults with type 1 diabetes mellitus were observed for the development of lipodystrophy. Injection technique, insulin dose, and glycemic parameters were noted. Serum TNF-α, IL-1ß, and anti-insulin antibody levels were measured. Histopathological examination of the lipodystrophic area was done in a small number of people. RESULTS: Among the participants, 45.2% of participants had lipohypertrophy and 4.2% had lipoatrophy exclusively; 3.1% of participants had coexisting lipohypertrophy and lipoatrophy. Improper injection site rotation technique was more common in participants with lipohypertrophy in comparison to those without lipodystrophy. The age of onset of diabetes, duration of insulin use, and the number of times of needle reuse were not significantly different between the lipohypertrophy and nonlipodystrophy groups. Serum TNF-α, IL-1ß, and anti-insulin antibody levels; HbA1c; rate of hypoglycemia; and body weight-adjusted dose requirement were higher among the participants with lipohypertrophy. On histopathology, scant, or no inflammatory infiltrate was found in lipoatrophic and lipohypertrophic areas, respectively. CONCLUSION: Improper insulin injection technique and higher levels of proinflammatory cytokines and anti-insulin antibody are associated with lipodystrophy in type 1 diabetes mellitus. HbA1c and rate of hypoglycemia are higher in people with lipodystrophy.

Subclinical lipohypertrophy--Easily ignored complications of insulin therapy.

AIMS: Subclinical lipohypertrophy is a lesion meeting ultrasonic criteria for lipohypertrophy that was not detected by inspection and palpation. Little information is published on subclinical lipohypertrophy among insulin injection people with diabetes. We aimed to investigate the subclinical lipohypertrophy prevalence, risk factors, and the association between subclinical lipohypertrophy and glycemic control. METHODS: This observational study included 316 people with diabetes who had continuously received insulin therapy for at least one year. We performed ultrasound scanning and clinical examination for evidence of subclinical lipohypertrophy. Demographic characteristics, clinical information, and glycated hemoglobin were measured. RESULTS: The overall prevalence of subclinical lipohypertrophy was 19.9%. By stepwise logistic regression, higher BMI (OR = 1.44, 95%CI: 1.15-1.81, P = 0.002), incorrect rotation of sites (OR = 3.11, 95%CI: 1.02-9.47, P = 0.046), insulin needle reusage for more than four times (OR = 10.00, 95%CI: 3.23-31.02, P = 0.000) and type 1 diabetes (OR = 6.33, 95%CI: 1.32-30.47, P = 0.021) remained associated with subclinical lipohypertrophy. Subclinical lipohypertrophy demonstrated a significant independent correlation with the nonoptimal glycemic control (OR = 9.97, 95% CI: 3.46-28.75, P = 0.000) when accounting for demographic and diabetes-related parameters. CONCLUSIONS: Subclinical lipohypertrophy is common among insulin-injecting patients with diabetes and is related to glycemic control deterioration. Ultrasonography may be an ideal adjunct in the evaluation of easily ignored lipohypertrophy lesions, especially where poor glycemic control, incorrect injection behaviors, overweight or obesity are documented.

Insulin injection technique in the western region of Algeria, Tlemcen.

INTRODUCTION: Algeria has more than 1.7 million diabetic patients on to whom a descriptive assessment particularly on the insulin usage behaviors has not yet been initiated, although is needed. This study aims to provide a descriptive analysis of how Algerian diabetic patients perceive and apply insulin injection techniques. METHODS: using the "patient" questionnaire within the Injection Technique Questionnaire (ITQ) 2016 survey, this study assessed the insulin injection practices of 100 patients recruited over a seven-month period in western Algeria at the Tlemcen University Hospital Center. The results of this study are compared to those of the ITQ 2016 survey. RESULTS: pens are the instruments of injection for 98% of Algerians who continue to use mostly long needles of 6- and 8-mm, although 4mm needles are the recommended safer option. Insulin analogues (fast and basal) are plebiscite. Arms and thighs are the preferred injection sites; the abdomen (the preferred site elsewhere) is neglected for reasons to be investigated. The correct re-suspension technique for cloudy insulin is unknown. Extensive pen needle re-use (10+ times) for over half of the patients exposes them to both higher intramuscular (IM) injection risk and lipohypertrophy (LH). Injection training is performed in Algeria by the diabetologist. CONCLUSION: this study describes for the first time Algerian patients´ insulin injection technique. It highlights their skills and identifies many deficiencies which patients and professionals must correct given the issues in this area.

A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach.

AIMS: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS: We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

Lipodystrophic syndromes: From diagnosis to treatment.

Lipodystrophic syndromes are acquired or genetic rare diseases, characterised by a generalised or partial lack of adipose tissue leading to metabolic alterations linked to strong insulin resistance. They encompass a variety of clinical entities due to primary defects in adipose differentiation, in the structure and/or regulation of the adipocyte lipid droplet, or due to immune-inflammatory aggressions, chromatin deregulations and/or mitochondrial dysfunctions affecting adipose tissue. Diagnosis is based on clinical examination, pathological context and comorbidities, and on results of metabolic investigations and genetic analyses, which together determine management and genetic counselling. Early lifestyle and dietary measures focusing on regular physical activity and avoiding excess energy intake are crucial. They are accompanied by multidisciplinary follow-up adapted to each clinical form. In case of hyperglycemia, antidiabetic medications, with metformin as a first-line therapy in adults, are used in addition to lifestyle and dietary modifications. When standard treatments have failed to control metabolic disorders, the orphan drug metreleptin, an analog of leptin, can be effective in certain forms of lipodystrophy syndrome. Metreleptin therapy indications, prescription and monitoring were recently defined in France, representing a major improvement in patient care.