Abnormal Body Fat Distribution Research Articles

Investigation of the therapeutic effect of Hedan tablets on high-fat diet-induced obesity in rats by GC-MS technology and 16S ribosomal RNA gene sequencing.

Obesity is a persistent metabolic condition resulting from the excessive accumulation or abnormal distribution of body fat. This study aimed to establish an experimental rat model of obesity. The efficacy of treating obesity with Hedan tablets (HDT) was assessed by monitoring changes in weight, blood lipid levels, analyzing inflammatory factors, evaluating organ indices, and observing liver tissue pathology. Furthermore, we utilized 16S ribosomal RNA gene sequencing technology to explore changes in intestinal flora. In addition, GC-MS was used to measure fecal short-chain fatty acid (SCFA) content. The onset of obesity led to a significant decrease in the relative abundance of beneficial bacteria. Conversely, the administration of HDT demonstrated a substantial ability to increase the relative abundance of beneficial bacteria. Obesity resulted in a noteworthy reduction in total SCFAs, a trend significantly reversed in the HDT group. Through correlation analysis, it was determined that HDT mitigated the inflammatory response and improved blood lipid levels by augmenting the abundance of Lactobacillus, Limosilactobacillus, Ruminococcus, and Enterococcus. These particular intestinal flora were identified as regulators of SCFA metabolism, thereby ameliorating metabolic abnormalities associated with obesity. Moreover, HDT intervention elevated the overall fecal concentration of SCFAs, thereby improving metabolic disorders induced by obesity. The anti-obesity effects of HDT are likely attributable to their capacity to influence the composition of intestinal flora and boost SCFA levels in the intestine.

PSUN55 Abnormal Body Fat Distribution in Lean Individuals with Metabolic Abnormalities

Abstract Background Truncal obesity has long been considered an essential driver of metabolic abnormalities, but it is common for lean individuals with body mass index (BMI) <25 kg/m2 to have one or more metabolic abnormalities. We hypothesized that metabolically unhealthy lean (MUL) individuals have a different distribution of fat compared to their metabolically healthy lean (MHL) counterparts. Methods We performed a retrospective analysis of body composition data obtained from a repository of dual-energy X-ray absorptiometry scans performed during routine clinical practice at a University Bone Clinic. Metabolic data were retrieved from electronic medical records within one calendar year of the index scan. Those with at least 2 components of the metabolic syndrome: blood pressure >130/85 mmHg, triglyceride >150 mg/dL, HDL <50 mg/dL for women and <40 mg/dL for men, fasting plasma glucose >100 mg/dL (or HbA1c >5.7) were considered MUL, while those with 1 component or less were considered MHL. Waist circumference was not considered in this study. Adults with a BMI less than 25 kg/m2 were included in the analysis. Unadjusted and adjusted binary logistic regression were used to analyze the association between metabolic abnormalities and various anthropometric indexes. Results The study population consisted of 119 lean adults with a mean age of 62±14 years and a mean BMI of 22±1.9 kg/m2. Majority of participants were white (88%, n=105) and included postmenopausal women (85%, n=101). A large proportion were of Hispanic ethnicity (41%, n=70). There were 69 (58%) MHL and 50 (42%) MUL individuals. MUL and MHL groups had comparable percentage of total body fat (34±6.6 versus 34±5.6, p=0.360), fat mass index (8.2±1.6 versus 8.1±1.5, p=0.360) and appendicular lean mass (kg/m2) (5.9±0.8 versus 5.8±0.7, p=0.420). However, compared to MHL, MUL subjects had significantly higher visceral adipose tissue (cm2) (87±40 versus 9±29, p=0.004), trunk-to-leg fat ratio (0.89±0.18 versus 0.77±0.13, p<0.001), trunk-to-limb fat ratio (1.00±0.29 versus 0.82±0.18, p<0.001) and android-to-gynoid fat ratio (0.90±0.16 versus 0.81±0.15, p=0.010). After adjusting for age and sex, the odds of being MUL compared to MHL (odds ratio [OR (95% confidence interval (CI))]) increased for every standard deviation increase in visceral adipose tissue (OR=1.75 [1.13-2.73]), trunk-to-leg fat ratio (OR=2.28 [1.30-4.00]), trunk-to-limb fat ratio (OR=2.43 [1.37-4.32]) and android-to-gynoid fat ratio (OR=1.80 [1.07-3.03]). Conclusion Metabolically unhealthy subjects with normal BMI had markedly increased visceral adipose tissue and truncal redistribution of body fat without an increase in total body fat. These findings highlight the importance of using body morphometry measures, rather than total body fat, to assess CVD risk in lean individuals. Our findings suggest that the phenotype of lean individuals with metabolic derangements is not very different from that of obese individuals who have metabolic syndrome as per the National Cholesterol Education Program Adult Treatment Panel-III definition. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Comparison The Effects of Endurance and Resistance Exercise On Static and Dynamic Balance in Obese Adolescent Boys

The pathological condition of obesity has an effect on quality of life. Larger body size, greater body mass index, abnormal body fat distribution, and the potential for neuromuscular disorders in obese children contribute to their body instability, resulting in poor static and dynamic stability. Poor body stability in obese adolescents can lead to a higher risk of falls and fractures. Daily physical activity and exercise are the main solutions to deal with balance problems in obese individuals. The exercise intervention that is often recommended for obese children and adolescents is endurance training, but the level of compliance is low because it takes a long time. Resistance training is an alternative that can be given but requires supervision to avoid the risk of injury. The purpose of this study was to compare the effects of endurance and resistance training on static and dynamic balance in obese adolescent boys. This study was conducted from July 2020 to September 2020. The subjects were adolescent boys aged 14-18 years with an age-appropriate body mass index (CDC BMI chart 2000) > P95. Twenty-five subjects were randomized into two groups, endurance and resistance groups. Frequency resistance training 3 times a week for 8 weeks. The intensity was determined using the Borg scale, gradually increasing. Endurance training starts with light intensity and gradually increases to moderate intensity with aerobic exercise (zumba fitness) for 30-60 minutes, a frequency of 3 times a week for 8 weeks. This study was conducted without calorie restriction. The assessments include static balance with the Standing Stork test and dynamic balance with the Modified BASS Balance test. The static balance (KS) in the pre-intervention endurance group was 2.21?0.80, and post-intervention 3.93?1.44, significance 0.002, while the pre-intervention resistance group was 2.30?0.67 and post-intervention 4.05?1.66 significance 0.001. The dynamic balance (KD) data for the pre-intervention endurance group was 79.08?11.1 and post-intervention 94.17?6.29, significance 0.000, while the pre-intervention resistance group was 75.85?14.88 and post-intervention 95.38?6.29, significance 0.000. Changes in static and dynamic balance before and after intervention between the 2 groups of endurance and resistance training there was no significant difference with a p-value of 0.955 for static balance and a p-value of 0.288 for dynamic balance. Endurance training and resistance training regularly 3 times a week for 8 weeks can have an effect on improving static and dynamic balance in obese adolescent boys.

Adverse Effects of Refeeding on the Plasma Lipidome in Young Individuals With Anorexia Nervosa?

Refeeding is the cornerstone of anorexia nervosa (AN) treatment, but little is known regarding the optimal pace and dietary composition or possible adverse effects of current clinical practices. Plasma lipids may be a moderating factor underlying unfavorable refeeding effects in AN, such as an abnormal central body fat distribution. The objective of this study was to analyze the plasma lipidome in the acutely underweight state of AN before and after refeeding. Using high-throughput quantitative mass spectrometry-based shotgun lipidomics, we measured 13 lipid classes and 204 lipid species or subspecies in the plasma of young female patients with acute AN, before (n= 39) and after (n= 23) short-term weight restoration during an intensive inpatient refeeding program (median body mass index [BMI] increase= 26.4%), in comparison to those in healthy control participants (n= 37). Before inpatient treatment, patients with AN exhibited increased concentrations of cholesterol and several other lipid classes. After refeeding, multiple lipid classes including cholesterol and ceramides, as well as certain ceramide species previously associated with obesity or overfeeding, showed increased concentrations, and a pattern of shorter and more saturated triacylgycerides emerged. A machine learning model trained to predict BMI based on the lipidomic profiles revealed a sizable overprediction in patients with AN after weight restoration. The results point toward a profound lipid dysregulation with similarities to obesity and other features of the metabolic syndrome after short-term weight restoration. Thus, this study provides evidence for possible short-term adverse effects of current refeeding practices on the metabolic state and should inspire more research on nutritional interventions in AN.

Fatty liver is an independent risk factor for gallbladder polyps.

BACKGROUNDGallbladder polyps (GBPs) are known to be associated with obesity and metabolic diseases. However, to date, the relationship between GBPs and abnormal body fat distribution, such as fatty liver, visceral obesity, or sarcopenia, has not yet been established.AIMTo evaluate whether GBPs are associated with fatty liver, visceral obesity, or sarcopenia.METHODSWe retrospectively reviewed the medical records of subjects who underwent various laboratory tests, body composition measurement with a non-invasive body composition analyzer, and abdominal ultrasonography during health checkups. A total of 1405 subjects with GBPs were compared with 2810 age- and sex-matched controls.RESULTSThe mean age of the subjects was 46.8 ± 11.7 years, and 63.8% were male. According to multiple logistic regression analysis, the presence of fatty liver [odds ratio (OR) 1.413; 95% confidence interval (CI) 1.218-1.638; P < 0.001] was an independent risk factor for GBP, together with low levels of alanine aminotransferase (OR 0.993; 95%CI 0.989-0.996; P < 0.001). Additionally, fatty liver showed both independent (OR 1.629; 95%CI, 1.335-1.988; P < 0.001) and dose-dependent (moderate to severe fatty liver; OR 2.137; 95%CI, 1.662-2.749; P < 0.001) relationship with large GBPs (≥ 5 mm). The presence of sarcopenia and high visceral fat area were not significantly associated with GBPs.CONCLUSIONFatty liver was found to be closely associated with GBPs irrespective of sarcopenia and visceral obesity.

MON-685 Lipodystrophy, a Forgotten Syndrome

Background: Lipodystrophy comprises a group of heterogenous congenital and acquired disorders. These disorders may present as a complete or partial loss of adipose tissue. The magnitude of lipoatrophy correlates with the severity of the associated metabolic disturbances, which include severe insulin resistance, progressive liver disease, severe dyslipidemia, among others. The most prevalent form of lipodystrophy is related to antiviral use in patients with HIV. However, lipodystrophy occurring unrelated to medication side effect is often missed due to the heterogeneity and rarity of this disorder. Clinical Case: 31 year old female with medical history of type 2 diabetes mellitus, hypertension, mixed dyslipidemia and polycystic ovarian syndrome who was referred to our clinics due to difficult to control hyperglycemia. Family history was limited. She was diagnosed with diabetes mellitus at 12 years old after presenting with polyuria, polydipsia and polyphagia requiring oral antidiabetic therapy. Following poor response, she was started on insulin therapy. At 23 years old, the patient had an episode of pancreatitis associated with hypertriglyceridemia and eruptive xanthomas. Insulin pump therapy with regular U-100 insulin, total daily dose of 308 units, was initiated but failed to improve glycemic control. The patient was referred to our Endocrinology clinics due to high insulin resistance and a glycosylated hemoglobin (A1C) at 12% (n < 6.5%). Physical examination revealed a body mass index of 23 kg/m2, abnormal fat distribution predominantly over the neck and face, and acanthosis nigricans. Abdominal ultrasound revealed fatty liver infiltration consistent with intrabdominal fat deposition. Due to the constellation of the aforementioned findings, the diagnosis of partial lipodystrophy syndrome was presumed. She was started on antidiabetic therapy with metformin, pioglitazone and insulin pump therapy with U-500 insulin, and high-dose statin therapy plus fenofibrate for dyslipidemia. At follow up, the patient showed improvement in glycemic control and an improved lipid profile. She was referred to a geneticist for evaluation. Conclusion: Lipodystrophy syndromes are a group of heterogenous disorders, which may often be overlooked due to their rarity and lack of familiarity by physicians. The diagnosis of lipodystrophy is based on history, abnormal body fat distribution, and metabolic profile. The metabolic disturbances seen in these patients are mainly due to the lack of adipose tissue, which results in impaired energy storage. Early recognition of these syndromes is important because intensive treatment of hyperlipidemia and diabetes prevents development of severe complications. In this case we highlight this rare condition and the successful use of new therapeutic technology with insulin pumps and U-500 insulin in the glycemic control of a patient with lipodystrophy.

Lipedema: A Call to Action!

Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.

Atherogenic Index of Plasma is Associated with Body Fat Level in Type 2 Diabetes Mellitus Patients.

To investigate the characteristics of body fat distribution and the relationship between body fat index and Atherogenic Index of Plasma (AIP) in Type 2 Diabetes Mellitus (T2DM) patients. A total of 316 participants were divided into a T2DM group and a non-diabetes group (controls). According to the Visceral Fat Area (VFA), all participants were further divided into VFA ≥100 cm2 and VFA <100 cm2 groups. To compare the differences of blood lipid, blood glucose, body fat index and AIP between the 2 groups, single factor correlation analysis was used to determine the correlation between the indexes and AIP, and multiple linear regression was used to analyse the correlation between the related factors and AIP. The body fat index (including body fat content, Percentage of Body Fat (PBF), Waist to Hip Fat Ratio (WHR) and VFA), Triglyceride (TG), Fasting Insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and AIP in T2DM group were significantly higher than in the control group, while High Density Lipoprotein Cholesterol (HDL-C) level was significantly higher in the control group. In the VFA≥100 cm2 group, TG, Low Density Lipoprotein Cholesterol (LDL-C), FINS, HOMAIR and AIP were all higher than that in the VFA <100 cm2 group. There was a positive correlation between AIP and VFA, body fat content, percentage of body fat, and WHR, respectively. There was also a negative correlation between AIP and HDL-C, which was not related to age, sex, Fasting Glucose (FPG), glycosylated haemoglobin (HbA1c), Total Cholesterol (TC), LDL-C and course of disease. Compared with the VFA <100 cm2 group, the VFA ≥100 cm2 group had higher blood Uric Acid (UA) levels and UA was positively correlated with VFA. After correcting the effect of UA on AIP, VFA was still an independent related factor of AIP, and VFA increased the risk of atherosclerosis by increased UA. T2DM patients have the abnormal distribution of body fat and a high VFA, which was associated with AIP.

The Association of Fat and Lean Tissue With Whole Body and Spine Bone Mineral Density Is Modified by HIV Status and Sex in Children and Youth.

HIV-infected (HIV-pos) male children/youth showed lower bone mineral density at sexual maturity than HIV-uninfected (HIV-neg) females. It is not known whether complications of HIV disease, including abnormal body fat distribution, contribute to lower bone accrual in male HIV-pos adolescents. In a cross-sectional study, we evaluated the relationship between body composition (fat and lean mass) and bone mass in HIV-pos and HIV-neg children/youth and determined if it is modified by HIV status and sex. We used generalized estimating equations to simultaneously model the effect of fat/lean mass on multiple bone outcomes, including total body bone mineral density and bone mineral content and spine bone mineral density. We evaluated effect modification by HIV and sex. The analysis cohort consisted of 143 HIV-neg and 236 HIV-pos, of whom 55% were black non-Hispanic and 53% were male. Ages ranged from 7 to < 25 years. Half of the children/youth were at Tanner stage 1 and 20% at Tanner 5. Fat mass was more strongly positively correlated with bone mass in HIV-neg than HIV-pos children/youth and these relationships were more evident for total body bone than spine outcomes. Within HIV strata, fat mass and bone were more correlated in female than male children/youth. The relationship between lean mass and bone varied by sex, but not by HIV status. HIV disease diminishes the positive relationship of greater fat mass on bone mass in children/youth. Disruptions in body fat distribution, which are common in HIV disease, may have an impact on bone accretion during pubertal development.

Neck circumference as a discriminator of obesity in older women enrolled in a physical activity program

The aim of this study was to evaluate neck circumference (NC) as a discriminator of overweight and obesity and to establish cut-off points for physically active older women. The sample consisted of 170 older women (69.5 ± 6.8 years) practicing physical activity. Anthropometric measures (body weight, height, waist circumference – WC, and NC) were obtained and the body mass index (BMI) was calculated. Correlation analysis was performed and ROC curves were constructed. NC was significantly correlated with BMI (rho = 0.656; p&lt;0.0001) and WC (r = 0.561; p&lt;0.0001). Correlating BMI with NC, areas under the ROC curve of 0.819 (p=0.0001) for overweight and of 0.902 (p=0.0001) for obesity were obtained, with suggested cut-off points of 33.07 and 34.05 cm, respectively. Correlating WC with NC, areas under the ROC curve of 0.711 (p=0.0014) for moderate risk (WC) and of 0.864 (p=0.0001) for high risk were obtained, with suggested cut-off points of 32.15 and 34.15 cm, respectively. NC was associated with BMI and WC. An NC ≥ 34 cm was a risk factor for obesity and abnormal body fat distribution in the older women studied. This anthropometric parameter is an alternative to discriminate overweight and obesity in physically active older women.

The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol

BackgroundWith potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals.Methods/designThe Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile.DiscussionThe Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV.

Nonobese, Nonketotic Childhood-Onset Diabetes: Look for Lipodystrophies.

Diabetes in children and youth poses a unique diagnostic and therapeutic challenge. Although type 1 and type 2 diabetes are undoubtedly the most frequently encountered forms of diabetes, other forms are not uncommon in this age-group. Many young patients with so-called “specific types of diabetes due to other causes” may be misdiagnosed as having type 1 or type 2 diabetes because of a lack of awareness of the various diagnostic possibilities (1). The group of patients with other forms of diabetes constitutes <5% of all patients diagnosed with diabetes before the age of 25 years and includes a variety of conditions (2). Lipodystrophy, a group of disorders characterized by loss or abnormal distribution of body fat, is associated with insulin resistance and resultant abnormal glucose homeostasis. Depending on the extent of the loss of adipose tissue, these rare disorders are divided into three subgroups: generalized, partial, and localized. Barring the localized form, the other variants are associated with profound metabolic dysfunction. These disorders can be inherited or can be acquired secondary to a number of infectious or immunological diseases and can potentially be associated with diabetes. Patients with lipodystrophies are often misdiagnosed as having type 2 diabetes and occasionally as having type 1 diabetes. The prevalence of partial lipodystrophy was found to be 0.79% in patients initially misdiagnosed as having type 2 diabetes (3). We describe here two patients with childhood-onset diabetes secondary to congenital lipodystrophies and discuss their clinical and diagnostic features. ### Case 1 A 6-year-old girl born of a consanguineous union had been detected to have diabetes while undergoing evaluation for failure to gain weight. She was placed on insulin by her primary care physician and referred to us for unsatisfactory glycemic control despite receiving a high dosage of insulin (3.7 units/kg; total daily dose: 52 units). She did …

Type 1 familial partial lipodystrophy: understanding the Köbberling syndrome.

Familial partial lipodystrophy are Mendelian disorders involving abnormal body fat distribution and insulin resistance. The current classification includes the Köbberling syndrome (type 1 familial partial lipodystrophy), characterized by fat loss in the lower limbs and abnormal fat accumulation in other areas. Type 1 familial partial lipodystrophy appears to be heritable, but little is known about it, including putative contributing mutations. We aimed to characterize this syndrome better by evaluating a group of women with phenotypic features of type 1 familial partial lipodystrophy. This is a case-controlled study in which 98 women with type 1 familial partial lipodystrophy that lacked classical mutations known to cause familial partial lipodystrophy were compared with 60 women without lipodystrophy and 25 patients with type 2 familial partial lipodystrophy (Dunnigan disease). Clinical course, body composition by dual-energy X-ray absorptiometry, HbA1c, lipid profile, insulin, leptin and family history were evaluated in all of the participants. Analyses of receiver-operating characteristic curve were performed for type 1 familial partial lipodystrophy diagnosis, comparing different truncal/limbs ratios. Among patients with type 1 familial partial lipodystrophy, 68 % developed recognizable lipodystrophy before adolescence, and most displayed an autosomal-dominant pattern (86 %). Women with type 1 familial partial lipodystrophy had less lower-limb adipose tissue than women without lipodystrophy, but significantly more than patients with Dunnigan disease. Moreover, metabolic disturbances occurred more frequently in the type 1 familial partial lipodystrophy group (81 %) than in the non-lipodystrophic group (30 %, p<0.05). The severity of metabolic disturbances was inversely proportional to the percentage of fat in the lower extremities and directly proportional to the amount of visceral adipose tissue. Metabolic profiles were worse in type 1 familial partial lipodystrophy than in Dunnigan disease. According to the receiver-operating characteristic curve analysis, the best ratio was subscapular/calf skinfolds (KöB index), with a cut-off value of 3.477 (sensitivity: 89 %; specificity: 84 %). Type 1 familial partial lipodystrophy was an early-onset, autosomal-dominant lipodystrophy, characterized by fat loss in the lower limbs and abnormal fat accumulation in the abdominal visceral region, associated to insulin resistance and metabolic disorders. A KöB index >3.477 is highly suggestive of this syndrome.

Determinants of C-reactive protein concentrations in pregnant women with type 1 diabetes.

INTRODUCTION Increased C-reactive protein (CRP) concentrations during pregnancy are associated with several perinatal complications. OBJECTIVES The aim of the study was to assess serum CRP concentrations and identify its determinants in pregnant women with type 1 diabetes. PATIENTS AND METHODS CRP concentrations were determined using a high-sensitivity assay (hs-CRP) in the first trimester (I, week <12 of gestation), in mid-pregnancy (II, weeks 20 to 24 of gestation), and in the late third trimester (III, weeks 34 to 39 of gestation) in a group of 73 patients with type 1 diabetes. RESULTS There was a significant increase in CRP concentrations between the first trimester and mid‑pregnancy (median [interquartile range], 2.5 mg/l [1.3-4.5 mg/l] and 5.6 mg/l [2.5-11.6 mg/l]; P = 0.0001), which then stabilized with no further change between mid-pregnancy and the late third trimester (5.7 mg/l [2.5-9.6 mg/l]). CRP concentrations in all 3 trimesters were positively correlated with the waist‑to-hip ratio (I, P <0.0001; II, P = 0.0004; III, P = 0.0369) and body mass index (I, P = 0.015; II, P = 0.0025; III, P = 0.0048), measured in the first trimester. CRP concentrations during pregnancy were positively correlated with a measure of insulin resistance, namely, the estimated glucose disposal rate, assessed in the first trimester (I, P = 0.01; II, P = 0.0165; III, P = 0.0062). There was a positive correlation between the levels of hs-CRP and total cholesterol (P = 0.001), low-density lipoprotein cholesterol (P = 0.013), and triglycerides (P = 0.0014) in the first trimester. There was no significant correlation between CRP and hemoglobin A1c, daily insulin requirement/kg, high-density lipoprotein cholesterol levels, maternal age, and diabetes duration. CONCLUSIONS Adiposity, abnormal body fat distribution, and insulin resistance are the major determinants of CRP concentrations in pregnant women with type 1 diabetes. Our results confirm the importance of weight control before pregnancy in women with type 1 diabetes.

Mildly compromised tetrahydrobiopterin cofactor biosynthesis due to Pts variants leads to unusual body fat distribution and abdominal obesity in mice.

Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, alkylglycerol monooxygenase, and nitric oxide synthases (NOS). Inborn errors of BH4 metabolism lead to severe insufficiency of brain monoamine neurotransmitters while augmentation of BH4 by supplementation or stimulation of its biosynthesis is thought to ameliorate endothelial NOS (eNOS) dysfunction, to protect from (cardio-) vascular disease and/or prevent obesity and development of the metabolic syndrome. We have previously reported that homozygous knock-out mice for the 6-pyruvolytetrahydropterin synthase (PTPS; Pts-ko/ko) mice with no BH4 biosynthesis die after birth. Here we generated a Pts-knock-in (Pts-ki) allele expressing the murine PTPS-p.Arg15Cys with low residual activity (15% of wild-type in vitro) and investigated homozygous (Pts-ki/ki) and compound heterozygous (Pts-ki/ko) mutants. All mice showed normal viability and depending on the severity of the Pts alleles exhibited up to 90% reduction of PTPS activity concomitant with neopterin elevation and mild reduction of total biopterin while blood L-phenylalanine and brain monoamine neurotransmitters were unaffected. Yet, adult mutant mice with compromised PTPS activity (i.e., Pts-ki/ko, Pts-ki/ki or Pts-ko/wt) had increased body weight and elevated intra-abdominal fat. Comprehensive phenotyping of Pts-ki/ki mice revealed alterations in energy metabolism with proportionally higher fat content but lower lean mass, and increased blood glucose and cholesterol. Transcriptome analysis indicated changes in glucose and lipid metabolism. Furthermore, differentially expressed genes associated with obesity, weight loss, hepatic steatosis, and insulin sensitivity were consistent with the observed phenotypic alterations. We conclude that reduced PTPS activity concomitant with mildly compromised BH4-biosynthesis leads to abnormal body fat distribution and abdominal obesity at least in mice. This study associates a novel single gene mutation with monogenic forms of obesity.

Metabolic and cardiovascular effects of combined antiretroviral therapy in patients with HIV infection. Systematic review of literature

In HIV infected patients an increased incidence of cardiac events has been reported since the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the frequent presence in this population of traditional risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurrence of carotid vascular impairment in patients treated with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk was independently associated with longer exposure to PI, after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adequate control of drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metabolic effects of antiretroviral drugs and on the contribution of combination antiretroviral therapy on cardiovascular risk.

Exploratory study of total and free prednisolone plasma exposure and cushingoid appearance, quality of life and biochemical toxicity in adult male kidney transplant recipients.

Long-term adverse effects of oral glucocorticoids are frequent and serious. Large between-patient variability in the pharmacokinetics of prednisolone might explain why drug dose is a poor predictor of drug-related toxicity. The aim of the study was to investigate relationships between prednisolone exposure and adverse effects. Male kidney transplant recipients were recruited for serial blood sampling and assessment of glucocorticoid-related adverse effects including dyslipidaemia, abnormal body fat distribution, Cushingoid appearance and impaired quality of life. Total and free prednisolone plasma concentrations were determined using ultra-high-performance liquid chromatography with tandem mass spectrometric detection. Prednisolone exposure was estimated using a limited sampling strategy. Fifty-six patients were recruited. Patients had a mean age of 54 years and median time post-transplantation of 75 months. Median prednisolone dose was 5 mg. Mean area under the plasma concentration-time curve was 2390 nmol h/L (±580) (SD) and 175 nmol h/L (±78) for total and free prednisolone, respectively. Waist to upper arm circumference ratio was positively associated with free prednisolone plasma exposure with a Spearman correlation coefficient of 0.30 (p value 0.02). The correlation coefficient was 0.24 (p value 0.08) for neck to upper arm circumference ratio and free prednisolone plasma exposure. The clinical Cushingoid phenotype as determined by the Visual Assessment of Cushing's Severity (VACS) score was associated with a reduced score relating to physical functioning on the SF-12, but there was no significant relationship between free prednisolone plasma exposure and quality-of-life scores. Lipid levels and haemoglobin A1c (HbA1c) were not associated with total or free prednisolone exposure. There is a positive correlation between free prednisolone plasma exposure and waist to upper arm circumference ratio in adult male kidney transplant recipients on low maintenance prednisolone doses. There is no significant association between total or free prednisolone plasma exposure and plasma glucose and lipid levels in the low prednisolone dose range.

Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.

Association of HSD11B1 polymorphic variants and adipose tissue gene expression with metabolic syndrome, obesity and type 2 diabetes mellitus: a systematic review.

The HSD11B1 gene is highly expressed in abdominal adipose tissue, and the enzyme it encodes catalyzes the interconversion of inactive cortisone to hormonally active cortisol. Genetic abnormalities of HSD11B1 have been associated with the development of abnormal glucose metabolism and body fat distribution. To systematically review studies evaluating the association of HSD11B1 gene expression in abdominal adipose tissue and HSD11B1 polymorphisms with obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM), we conducted a search in MEDLINE, SCOPUS, and Cochrane Library databases in April 2015. The inclusion criteria were observational studies (cross-sectional, cohort, or case–control), conducted in adults, which analyzed the relationship of HSD11B1 polymorphisms and/or HSD11B1 expression in abdominal adipose tissue with obesity, MetS, or T2DM. Of 802 studies retrieved, 32 met the inclusion criteria (23 gene expression and 9 polymorphism studies). Twenty one studies analyzed the relationship between abdominal subcutaneous and/or visceral HSD11B1 expression with central and/or generalized obesity. Most studies reported that abdominal adipose HSD11B1 expression increased with increasing body mass index (15 studies) and abnormalities of glucose metabolism (7 studies), and varied with the presence of MetS (3 studies). Nine studies analyzed the association of 26 different HSD11B1 polymorphic variants with obesity, MetS, and T2DM. Only an Indian study found an association between a polymorphic variant at the HSD11B1 gene with MetS whereas in Pima Indians another polymorphic variant was found to be associated with T2DM. While the literature suggests that HSD11B1 is hyperexpressed in abdominal adipose tissue in subjects with obesity and abnormal glucose metabolism, this seems to be not true for HSD11B1 gene expression and MetS. Although an association of polymorphic variants of HSD11B1 with MetS in Indians and in the T2DM population of Pima Indians were found, most studies did not find a relationship between genetic polymorphic variants of HSD11B1 and obesity, MetS, and T2DM. Their reported conflicting and inconclusive results, suggesting that polymorphic variants of HSD11B1 may have only a small role in the development of metabolic abnormalities of susceptible populations in the development of MetS and T2DM.

Switching from zidovudine/lamivudine to tenofovir/emtricitabine improves fat distribution as measured by fat mass ratio.

Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.