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Background . Obesity is a global health problem of epidemic proportions, which is characterized by increased adipose tissue (AT) mass and significant repercussions in different body apparati and systems. AT is a special connective tissue, which contains several types of cells, in addition to adipocytes, and is a highly active endocrine and immune organ, which directly modulates many processes, including energy balance, metabolism, and inflammation. Summary . In this paper, the authors list and attempt to answer in a brief and simple way several questions regarding the complex relationships between obesity, adipose tissue, and inflammation, with the objective to provide an easy way to understand the main changes that occur in this pathological state. The questions are the following: Is adipose tissue only made up of adipocytes? Are adipocytes just a reservoir of free fatty acids? Do different types of fatty tissue exist? If so, which types? Can we further subcategorize the types of adipose tissue? Is it possible to form new adipocytes during adulthood? What is the role of inflammation? What is the role of macrophages? Are macrophages central mediators of obesity-induced adipose tissue inflammation and insulin resistance? What causes macrophage infiltration into adipose tissue? What is the role of hypoxia in AT alterations? Is there cross talk between adipocytes and immune cells? What other changes occur in AT in obesity? Does metabolically healthy obesity really exist? Is this a benign condition? Key messages . Obesity is a complex disease with numerous metabolic consequences, which are mainly the result of dysfunction that occurs in the adipose tissue of patients with this pathology. Understanding the pathophysiology of AT and the changes that occur in obesity would contribute to a better approach to patients with obesity, with the inherent medical implications that could result from this., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Vanessa A. Guerreiro et al.)

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain., Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity., Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery)., Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = -1.04 [-1.82 to -0.26], p<0.01; β = -1.16 [-2.13 to -0.19], p=0.02; β = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery., Conclusion: β-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Borges-Canha, Neves, Mendonça, Silva, Costa, M. Cabral, Guerreiro, Lourenço, Meira, Salazar, Ferreira, Pedro, Barkoudah, Sande, Lau, B. Souto, Preto, Freitas and Carvalho.)

Background: Lipodystrophic syndromes are uncommon medical conditions which are normally associated with metabolic disorders, such as diabetes mellitus, dyslipidemia, and fatty liver disease. These complications are generally difficult to treat, particularly diabetes, due to severe insulin resistance. We present two case reports of successful treatment of diabetes with glucagon-like peptide-1 analogues in patients with clinical features of lipodystrophic syndromes., Case Presentation: Two white women aged 49 and 60 years manifested marked central body fat deposition with severe lipoatrophy of their limbs and buttocks and pronounced acanthosis nigricans. They had hypertension, dyslipidemia, fatty liver disease, and poorly controlled diabetes (glycated hemoglobin 8.3% and 10.2%, respectively) despite the use of three classes of oral antidiabetic drugs taken in combination in the first case, and high doses of insulin in the second case. Four months after the addition of glucagon-like peptide-1 analogue to their previous treatment they both showed a pronounced improvement in metabolic control (glycated hemoglobin 5.6% and 6.2%, respectively). In the first case, a weight loss of nearly 30 kg was recorded., Conclusions: We intend to demonstrate that glucagon-like peptide-1 analogues could be a valuable tool for patients with lipodystrophic disorders, probably by improving body fat distribution, with favorable results in insulin-sensitivity and glycemic control.

Background: Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution., Methods: Anthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient's fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation., Results: Leptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching., Conclusion: The overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.

Introduction: Combined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes., Aims: To compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio) and different patterns of fat distribution and to establish their associations., Design: Cross-sectional cohort study., Methods: We evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults., Results: Patients with clinical lipodystrophy (CL) had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4) was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA) was found., Conclusions: IR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition.

Background: Lipodystrophies are a group of diseases which are characterized by abnormal adipose tissue deposition and are frequently associated with metabolic changes. Congenital generalized lipodystrophy is an autosomal recessive syndrome, with a prevalence < 1:10 million. Acromegaly is a rare disease, secondary to the chronic hypersecretion of growth hormone and insulin-like growth factor-1, with characteristic metabolic and somatic effects. "Acromegaloidism" is a term used for patients who manifest clinical features of acromegaly, but do not present a demonstrable hormone growth hypersecretion. The extreme shortage of subcutaneous adipose tissues and muscle hypertrophy confer an acromegaloid-like appearance in these patients.Case Presentation: We describe a case of a patient with the rare combination of Berardinelli-Seip congenital lipodystrophy and acromegaly; our patient is a 63-year-old white man, who was referred to an endocrinology consultation for suspected lipodystrophy. He had lipoatrophy of upper and lower limbs, trunk, and buttocks, with muscular prominence, acromegaloid facial appearance, large extremities, and soft tissue tumescence. In addition, he had dyslipidemia and prediabetes. His fat mass ratio (% trunk fat mass/% lower limbs fat mass) was 1.02 by densitometry and he also had hepatomegaly, with mild steatosis (from an abdominal ultrasound), and left ventricular hypertrophy (from an electrocardiogram). His first oral glucose tolerance test had growth hormone nadir of 0.92 ng/mL, and the second test, 10 months afterwards, registered growth hormone nadir of 0.64 ng/mL (growth hormone nadir < 0.3 ng/mL excludes acromegaly). Pituitary magnetic resonance imaging identified an area of hypocaptation of contrast product in relation to a pituitary adenoma and he was subsequently submitted to transsphenoidal surgical resection of the mass. A pathological evaluation showed pituitary adenoma with extensive expression of growth hormone and adrenocorticotropic hormone, as well as a rare expression of follicle-stimulating hormone and prolactin. A genetic study revealed an exon 3/exon 4 deletion of the AGPAT2 gene in homozygosity.Conclusions: Congenital generalized lipodystrophy is a rare disease which occurs with acromegaloid features. As far as we know, we have described the first case of genetic lipodystrophy associated with true acromegaly. Although this is a rare association, the presence of congenital generalized lipodystrophy should not exclude the possibility of simultaneous acromegaly. [ABSTRACT FROM AUTHOR]

Background: Human lipodystrophies are uncommon disorders, with important clinical consequences, which are often undiagnosed. The Barraquer-Simons syndrome is a form of partial symmetric lipodystrophy of unknown etiology, characterized by the loss of subcutaneous adipose tissue, limited to upper part of the body. Insulin resistance and metabolic complications are less common than with other lipodystrophy subtypes. Patients usually have decreased serum complement-component 3 levels, associated with complement activation by the alternative pathway, which may indicate the presence of renal involvement. Case presentation: The authors report a case of a 31-year-old woman with progressive loss of subcutaneous fat, limited to the face, neck and thorax. She presented no severe metabolic complications, neither signs of insulin resistance. Laboratory tests revealed mild dyslipidemia, and low serum levels of complement-component 3. Clinical and biochemical characteristics were consistent with the diagnosis of Barraquer-Simons syndrome. Conclusion: The present case illustrates the importance of recognizing the clinical features of this lipodystrophic syndrome, which may present potentially severe consequences and psychological distress. A brief overview is made, addressing the clinical signs of the disease, its course, and how to manage it. [ABSTRACT FROM AUTHOR]

Background: Familial partial lipodystrophy, Dunnigan variety, is a recognised autosomal dominant disorder which is caused by heterozygous missense mutations in the lamin A/C gene. Dunnigan lipodystrophy is characterised by a variable loss of fat from the extremities and trunk, as well as an excess of subcutaneous fat in the chin and supraclavicular area. The associated metabolic abnormalities include: insulin resistance, diabetes, dyslipidaemia and low leptin levels. Case presentation: The authors studied the case of a 24-year-old caucasian pregnant woman, with a past medical history of acute pancreatitis, combined dyslipidaemia and diabetes mellitus. At 7 weeks of pregnancy she was referred to the outpatient endocrinology and obstetrics clinic for diabetes care. A physical examination revealed that she presented a loss of fat from the extremities and trunk and also had an excess of subcutaneous fat in the chin. Triglyceride levels were persistently high, and glycaemic control was only achieved through the administration of high doses of insulin (1.8 U/Kg/day). Dunnigan lipodystrophy was suspected and thus a genetic study was requested, which revealed the presence of c.1444C > T (p.Arg482Trp) heterozygote mutation in the lamin A/C gene. Conclusion: This case is used to illustrate the importance of being able to recognise the clinical signs of this rare lipodystrophic syndrome, which may cause potentially severe consequences, and also the difficulties in treating it during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy dramatically reduced HIV-related morbidity and mortality, prolonging the lifespan of HIV-infected patients. Greater duration of infection and exposure to antiretroviral therapy makes these patients susceptible to traditional cardio-metabolic risk factors and pathologies. The optimal diagnostic protocol for Diabetes Mellitus in these patients is still controversial. Haemoglobin A1c (HbA1c) has been shown to underestimate glycaemia levels and the oral glucose tolerance test (OGTT) has been shown to reveal cases of glucose metabolism disturbances in patients with normal fasting glucose. Thus, this study aimed to determine the prevalence of prediabetes and diabetes in a population of HIV-infected patients undergoing combined antiretroviral therapy, using three different diagnostic methods (fasting glucose, OGTT and HbA1c), to determine the agreement between the different methods and the characteristics associated with each one.Methods: This study analyzed 220 HIV-infected patients on antiretroviral therapy. Patient characteristics were collected using a standardized protocol. Disturbances of glucose homeostasis were defined by the ADA 2017 criteria. Patients were characterized according to the presence or absence of clinical lipodystrophy, and distributed into four different categories, according to the presence, or absence of either clinical lipoatrophy, or abdominal prominence. Insulin resistance was assessed by HOMA-IR and QUICKI indexes. Agreement between the diagnostic methods was assessed by Cohen's kappa coefficient.Results: There were no patients diagnosed with diabetes with HbA1c. 5.9% prevalence was obtained when OGTT was used, and 3.2% prevalence when fasting glucose was used. Prediabetes had a prevalence of 14.1% when using HbA1c, 24.1% when using OGTT, and 20% when using fasting glucose. In all three methods, glucose homeostasis disturbances were associated with older age and higher resistance to insulin. Regarding other characteristics, associations varied between the three methods. The agreement between them was fair, or slight.Conclusions: We observed that HbA1c was the method that diagnosed the least amount of cases and that OGTT was the one that diagnosed the most cases. Accordingly, our results indicate that HbA1c underestimated glycaemia levels in this population and that the use of OGTT might allow an earlier diagnosis of glucose homeostasis disturbances, potentially making it possible to avoid severe complications of DM. [ABSTRACT FROM AUTHOR]