Anthropometric and Biochemical Correlations of Insulin Resistance in a Middle-Aged Maltese Caucasian Population.

Background: Insulin resistance (IR) is associated with increased cardiovascular disease risk, and with increased all-cause, cardiovascular, and cancer mortality. A number of surrogate markers are used in clinical practice to diagnose IR. The aim of this study was to investigate the discriminatory power of a number of routinely available anthropometric and biochemical variables in predicting IR and to determine their optimal cutoffs. Methods: We performed a cross-sectional study in a cohort of middle-aged individuals. We used receiver operator characteristics (ROC) analyses in order to determine the discriminatory power of parameters of interest in detecting IR, which was defined as homeostatic model assessment-insulin resistance ≥2.5. Results: Both the lipid accumulation product (LAP) and visceral adiposity index (VAI) exhibited good discriminatory power to detect IR in both males and females. The optimal cutoffs were 42.5 and 1.44, respectively, in males and 36.2 and 1.41, respectively, in females. Serum triglycerides (TG) and waist circumference (WC) similarly demonstrated good discriminatory power in detecting IR in both sexes. The optimal cutoffs for serum TG and WC were 1.35 mmol/L and 96.5 cm, respectively, in men and 1.33 mmol/L and 82 cm, respectively, in women. On the other hand, systolic and diastolic blood pressure, liver transaminases, high-density lipoprotein cholesterol, serum uric acid, ferritin, waist-hip ratio, "A" body shape, thigh circumference, and weight-adjusted thigh circumference all had poor discriminatory power. Conclusions: Our data show that LAP, VAI, TG, and WC all have good discriminatory power in detecting IR in both men and women. The optimal cutoffs for TG and WC were lower than those currently recommended in both sexes. Replication studies are required in different subpopulations and different ethnicities in order to be able to update the current cut points to ones which reflect the contemporary population as well as to evaluate their longitudinal relationship with longer-term cardiometabolic outcomes.

Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population.

BACKGROUND: Type 2 diabetes (T2DM) is genetically heterogenous, driven by beta cell dysfunction and insulin resistance. Insulin resistance drives the development of cardiometabolic complications and is typically associated with obesity. A group of common variants at eleven loci are associated with insulin resistance and risk of both type 2 diabetes and coronary artery disease. These variants describe a polygenic correlate of lipodystrophy, with a high metabolic disease risk despite a low BMI. OBJECTIVES: In this cross-sectional study, we sought to investigate the association of a polygenic risk score composed of eleven lipodystrophy variants with anthropometric, glycaemic and metabolic traits in an island population characterised by a high prevalence of both obesity and type 2 diabetes. METHODS: 814 unrelated adults (n = 477 controls and n = 337 T2DM cases) of Maltese-Caucasian ethnicity were genotyped and associations with phenotypes explored. RESULTS: A higher polygenic lipodystrophy risk score was correlated with lower adiposity indices (lower waist circumference and body mass index measurements) and higher HOMA-IR, atherogenic dyslipidaemia and visceral fat dysfunction as assessed by the visceral adiposity index in the DM group. In crude and covariate-adjusted models, individuals in the top quartile of polygenic risk had a higher T2DM risk relative to individuals in the first quartile of the risk score distribution. CONCLUSION: This study consolidates the association between polygenic lipodystrophy risk alleles, metabolic syndrome parameters and T2DM risk particularly in normal-weight individuals. Our findings demonstrate that polygenic lipodystrophy risk alleles drive insulin resistance and diabetes risk independent of an increased BMI.

Phenotyping obesity: A focus on metabolically healthy obesity and metabolically unhealthy normal weight.

Over the past 4 decades, research has shown that having a normal body weight does not automatically imply preserved metabolic health and a considerable number of lean individuals harbour metabolic abnormalities typically associated with obesity. Conversely, excess adiposity does not always equate with an abnormal metabolic profile. In fact, evidence exists for the presence of a metabolically unhealthy normal weight (MUHNW) and a metabolically healthy obese (MHO) phenotype. It has become increasingly recognised that different fat depots exert different effects on the metabolic profile of each individual by virtue of their location, structure and function, giving rise to these different body composition phenotypes. Furthermore, other factors have been implicated in the aetiopathogenesis of the body composition phenotypes, including genetics, ethnicity, age and lifestyle/behavioural factors. Even though to date both MHO and MUHNW have been widely investigated and documented in the literature, studies report different outcomes on long-term cardiometabolic morbidity and mortality. Future large-scale, observational and population-based studies are required for better profiling of these phenotypes as well as to further elucidate the pathophysiological role of the adipocyte in the onset of metabolic disorders to allow for better risk stratification and a personalised treatment paradigm.

Undifferentiated pleomorphic sarcoma of the spleen: a case report and literature review.

BACKGROUND: Undifferentiated pleomorphic sarcoma is an uncommon sarcoma and its presence in the spleen is even rarer, with only a handful of cases reported in English literature. It is typically only diagnosed following histological analysis. Its rarity also means that there is little consensus over ideal management. CASE PRESENTATION: This report presents a case of a 40-year-old Caucasian male who was found to have a splenic mass after presenting with non-specific abdominal pain and generalized malaise. Numerous imaging modalities were used which demonstrated a large partially solid and partially cystic lesion in spleen with no evidence of metastasis. As core biopsies were undiagnostic, he was planned for a diagnostic and therapeutic splenectomy. However, despite magnetic resonance imaging 11 days prior to his operation showed no evidence of liver metastasis, a massive splenic tumour with hepatic metastases was identified intraoperatively. An open splenectomy, distal pancreatectomy and liver metastasectomy was hence carried out. Histological analysis confirmed liver metastasis secondary to a splenic undifferentiated pleomorphic sarcoma. The patient recovered well and was discharged home. He presented again three weeks after his operation with lower back pain, abdominal pain and fever. Computed tomography demonstrated extensive recurrent disease burden in the peritoneum and liver. The patient passed away a month after surgery. CONCLUSION: Splenic undifferentiated pleomorphic sarcoma is a rare tumour which may pose a significant diagnostic challenge on both clinical and histopathological grounds. Following diagnosis and treatment, its aggressive nature often results in a poor prognosis. Current literature fails to delineate any superior management strategy to increase survival.

Investigating Adiposity-Related Metabolic Health Phenotypes in Patients with Hidradenitis Suppurativa: A Cross-Sectional Study.

BACKGROUND: Obesity and hidradenitis suppurativa (HS) are related through meta-inflammation and are both associated with increased cardiometabolic risk. Notwithstanding, cardiometabolic pathology is not uniform in obesity and a subset of individuals with excess adiposity exhibit a healthy metabolic profile. Whilst the incidence of cardiometabolic endpoints and transitions across different adiposity-related body composition phenotypes within several populations and across different ethnicities have been investigated, data regarding metabolic health (MetH) and body composition phenotypes in individuals with HS are lacking. The objective of this study was to evaluate the relationship between different body composition phenotypes in individuals with HS. METHODS: This was a cross-sectional study of 632 individuals with and without HS from a population with a high prevalence of both obesity and HS. A total of four body composition phenotypes were generated based on BMI and metabolic status (defined using either the metabolic syndrome definition or the homeostasis model of insulin resistance (HOMA-IR)): metabolically healthy overweight/obese (MHOWOB), metabolically unhealthy overweight/obese (MUOWOB), metabolically healthy normal weight (MHNW), and metabolically unhealthy normal weight (MUNW). RESULTS: Generally, subjects with HS exhibited a worse metabolic profile with higher levels of indices of central adiposity measures (including Visceral Adiposity Index and waist circumference), systolic blood pressure and markers of insulin resistance, as well as a higher prevalence of the metabolic syndrome. Moreover, when sub-stratified into the different body composition phenotypes, individuals with HS typically also demonstrated adverse metabolic characteristics relative to controls matched for both adiposity and metabolic health, particularly in the normal weight category and despite being classified as metabolically healthy. Being metabolically unhealthy in addition to being overweight/obese increases an individual's risk of HS. CONCLUSIONS: Metabolic risk-assessment should be prioritized in the clinical management of individuals with HS even in those who are lean. Patients attending HS clinics provide a valuable opportunity for targeted cardiovascular risk reduction with respect to the management of both obesity and metabolic health.

Obesity and hidradenitis suppurativa: targeting meta-inflammation for therapeutic gain.

Hidradenitis suppurativa (HS) is a chronic, inflammatory condition of the pilosebaceous unit. The typical patient with HS is characterized as someone with obesity, who smokes and who has nodules, abscesses and/or draining tunnels predominantly distributed in intertriginous skin. It has been established that lifestyle and genetic factors are the main pathophysiological drivers of HS. In this critical review, we explore the interrelatedness of meta-inflammation, obesity and HS and discuss if and how this relationship may be manipulated for a therapeutic end.

Reduced leukocyte mitochondrial copy number in metabolic syndrome and metabolically healthy obesity.

Objective: This study aimed to investigate the associations between peripheral blood leukocyte mitochondrial copy number, metabolic syndrome, and adiposity-related body composition phenotypes in a high prevalence population. Methods: A single center cross-sectional study was conducted, consisting of 521 middle-aged subjects of Maltese-Caucasian ethnicity. Participants were stratified according to the presence of metabolic syndrome and different metabolic health definitions based on NCEP-ATP III criteria. Relative leukocyte mitochondrial DNA copy number was determined by quantitative polymerase chain reaction and corrected for leukocyte and platelet count. The associations between mitochondrial copy number and metabolic syndrome components was evaluated and adjusted for age and gender. Results: Significant negative correlations between mtDNA copy number and BMI, waist circumference, triglyceride levels, fasting plasma glucose, HbA1c, HOMA-IR and hsCRP were observed, along with a positive correlation with HDL-C levels. Mitochondrial copy number was lower in individuals with metabolic syndrome. When compared to metabolically healthy normal weight subjects, a reduction in mtDNA copy number was observed in both the metabolically healthy and unhealthy obese categories. Conclusion: Our data supports the association between reduced leukocyte mtDNA copy number, obesity, and metabolic syndrome. This investigation expands on the spectrum of associations between mtDNA copy number and metabolic phenotypes in different populations and underpins the role of mitochondrial dysfunction in the development and progression of metabolic syndrome and its components.

Prevalence rates of metabolic health and body size phenotypes by different criteria and association with insulin resistance in a Maltese Caucasian population.

INTRODUCTION: Hyperinsulinemia and insulin resistance are known to be associated with increased cardiovascular morbidity and mortality. A metabolically unhealthy phenotype is frequently used as a surrogate marker for insulin resistance. The aims of the current study were to compare the prevalence of the body size phenotypes using different definitions of metabolic health and to investigate which one of them is most strongly associated with insulin resistance in men and women. METHODS: We conducted a cross-sectional study in a middle-aged cohort of Maltese Caucasian non-institutionalized population. Metabolic health was defined using the various currently used definitions. RESULTS: There were significant differences in the prevalence of body size phenotypes according to the different definitions. We also found significant sex differences in the predictive value of the various definitions of the metabolically unhealthy phenotype to predict insulin resistance. The strongest association was for the definition of having >2 NCEP-ATPIII criteria to characterize the metabolic unhealthy phenotype in women (odds ratio of 19.7). On the other hand, the Aguilar-Salinas et al. definition had the strongest association in men (odds ratio of 18.7). CONCLUSIONS: We found large differences in the prevalence of the various body size phenotypes when using different definitions, highlighting the need for having standard criteria. Our data also suggest the need for sex-specific definitions of metabolic health.

Sex differences in cardiometabolic abnormalities in a middle-aged Maltese population.

OBJECTIVES: There are sex differences in distribution of fat and in the prevalence of overweight and obesity. We therefore sought to explore sex differences in the prevalence of adiposity-metabolic health phenotypes, in anthropometric and cardio-metabolic parameters, and in the relationship between body mass index (BMI) categories and metabolic health. METHODS: We conducted a cross-sectional study carried out between January 2018 and June 2019, of a nationally representative sample of the Maltese Caucasian population aged 41 ± 5 years. Metabolic health was defined as presence of ≤ 1 parameter of the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III criteria. RESULTS: Males exhibited the unhealthy metabolic phenotype more frequently than women (41.3% vs 27.8%). In total, 10.3% of normal weight men and 6.3% of normal weight women were metabolically unhealthy. Males had a higher median BMI, but a lower proportion of males exhibited an abnormally high waist circumference as compared with females. A significant difference in sex distribution was noted for each body composition phenotype. CONCLUSION: In a contemporary sample of middle-aged individuals, males were more metabolically unhealthy and more insulin resistant than their female counterparts in spite of exhibiting an abnormal waist circumference less frequently and having similar waist index. This suggests that the currently used cut-offs for normal waist circumference should be revised downwards in men. Since even normal weight men were more often metabolically unhealthy than normal weight women, BMI cut-offs may also need to be lowered in men.

RéSUMé: OBJECTIFS: Il existe des différences entre les sexes dans la distribution de la graisse et dans la prévalence du surpoids et de l'obésité. Nous avons donc cherché à explorer les différences entre les sexes dans la prévalence des phénotypes d'adiposité et de santé métabolique, dans les paramètres anthropométriques et cardio-métaboliques et dans la relation entre les catégories d'indice de masse corporelle (IMC) et la santé métabolique. MéTHODES: Nous avons mené une étude transversale entre janvier 2018 et juin 2019, auprès d'un échantillon représentatif au niveau national de la population caucasienne maltaise âgée de 41 ans (± 5 ans). La santé métabolique a été définie comme la présence de ≤ 1 paramètre du syndrome métabolique tel que défini par les critères du National Cholesterol Education Program-Adult Treatment Panel III. RéSULTATS: Les hommes présentaient le phénotype métabolique malsain plus fréquemment que les femmes (41,3 % c. 27,8 %). 10,3 % des hommes de poids normal et 6,3 % des femmes de poids normal étaient métaboliquement malsains. Les hommes avaient un IMC médian plus élevé, mais une proportion plus faible d'hommes présentaient un tour de taille anormalement élevé par rapport aux femmes. Une différence significative dans la distribution des sexes a été notée pour chaque phénotype de composition corporelle. CONCLUSION: Dans un échantillon contemporain d'individus d'âge moyen, les hommes étaient plus malsains sur le plan métabolique et plus résistants à l'insuline que leurs homologues féminins, même s'ils présentaient moins souvent un tour de taille anormal et avaient un indice de taille similaire. Cela suggère que les seuils actuellement utilisés pour un tour de taille normal devraient être revus à la baisse chez les hommes. Puisque même les hommes de poids normal étaient plus souvent métaboliquement malsains que les femmes de poids normal, les seuils de l'IMC devraient peut-être aussi être revus à la baisse chez les hommes.

Characterisation of body size phenotypes in a middle-aged Maltese population.

Obesity is increasingly recognised as being a heterogeneous disease. Some obese individuals may present a metabolically healthy profile (metabolically healthy obese (MHO)), while some normal weight individuals exhibit an adverse cardiometabolic phenotype (metabolically unhealthy normal weight individuals (MUHNW)). The objectives of the present study were to examine the prevalence and associated characteristics of the different body composition phenotypes within a Maltese cohort. This was a cross-sectional analysis involving 521 individuals aged 41 ± 5 years. The metabolically unhealthy state was defined as the presence of ≥2 metabolic syndrome components (NCEP-ATPIII parameters), while individuals with ≤1 cardiometabolic abnormalities were classified as metabolically healthy. Overall, 70 % of the studied population was overweight or obese and 30⋅7 % had ≥2 cardiometabolic abnormalities. The prevalence of MHO and MUHNW was 10⋅7 and 2⋅1 %, respectively. Individuals with the healthy phenotype were more likely to consume alcohol, participate in regular physical activity and less likely to be smokers. While the MHO phenotype had similar values for waist, hip and neck circumferences, waist-hip ratio and insulin resistance when compared with MUHNW individuals, there was a lower proportion of MHO subjects having a high fasting plasma glucose, hypertriglyceridaemia or low HDL-C when compared with the unhealthy lean individuals. A high prevalence of the metabolically unhealthy phenotype was observed in this relatively young population which may result in significant future cardiovascular disease burden if timely assessment and management of modifiable risk factors are not implemented. Furthermore, the present study suggests that the MHO phenotype is not totally benign as previously thought.

The Bariatric-Metabolic Physician's Role in Managing Clinically Severe Obesity.

PURPOSE OF REVIEW: The aim of this review is to outline the obesity physician's role in managing patients with severe obesity with a particular emphasis on bariatric surgery candidates. RECENT FINDINGS: Obesity is a chronic, relapsing and progressive disease. Scoring systems that evaluate the severity of obesity based on the clinical assessment, rather than the Body Mass Index, are a valuable tool. The clinical assessment should explore the underlying contributors for weight gain and screen for obesity-related complications. Bariatric surgery remains the most effective management approach for severe and complex obesity. Nevertheless, pharmacotherapy and other non-surgical approaches play an important role. The bariatric-metabolic physician's role is paramount in delivering effective care to patients with obesity. The multiple complications of patients with clinically severe obesity highlight the complexity of their management and reinforce the need for adequate assessment and long-term follow-up to ensure optimal clinical outcomes.

Obesity and cardio-metabolic health.

Obesity is a major and growing global health problem. It is associated with increased mortality as a result of an increasing number of complications, including type 2 diabetes, dyslipidaemia, hypertension, non-alcoholic hepatic steatosis, cardiovascular disease, sleep apnoea, gallbladder disease, obesity-related renal disease, increased risk of falls and injuries, and mental health problems as well as increased risk of certain malignancies. This article discusses the metabolic derangements associated with obesity. These include insulin resistance, dysglycaemia, low and dysfunctional high-density lipoprotein, formation of small dense and oxidised low-density lipoprotein, and high circulating levels of free fatty acids. This article reviews the aetiology of these derangements and their relationship to cardiovascular disease, and discusses the concept of metabolic health.

Bone mineral density and intervertebral disc height in type 2 diabetes.

BACKGROUND: Studies of the effect of type 2 diabetes (T2D) on bone mineral density (BMD have produced conflicting results, possibly due to failure to adjust for potential confounding factors. Nonetheless, T2D has consistently been associated with increased fracture risk, suggesting that other factors might play a role. OBJECTIVE: This study assesses the relationship between T2D and BMD at the femoral neck and spine in diabetic and non-diabetic subjects, after adjusting for multiple covariates which may affect BMD. Intervertebral disc height was also investigated in view of its possible relation to fracture risk. METHODS: A cross-sectional study of 100 patients with T2DM of at least 5 years duration and 86 non-diabetic subjects was carried out. RESULTS: There were no significant differences in T scores in either the spine or femoral neck after adjustment for potential confounding variables between T2D subjects and controls. Diabetic patients had a statistically lower intervertebral disc height between the 2nd and 3rd lumbar vertebrae (D3) after adjustment for potential confounders (p=0.004). Urinary albumin:creatinine ratio, total cholesterol, LDL-cholesterol and cigarette smoking were independently associated with lower height of D3 in diabetic subjects. CONCLUSIONS: There is no significant independent association between T2D and BMD. However we found a novel association of significantly lower disc height in patients with T2D. This may contribute to the increased vertebral fracture risk in subjects with T2D. Further studies are needed to investigate the relationship of disc height, T2D and fracture risk.