Presence Of Metabolic Abnormalities Research Articles

Metabolic Abnormalities Following Tirzepatide Monotherapy in Japanese Patients with Type 2 Diabetes: A Phase 3 SURPASS J-mono Post Hoc Analysis.

The presence of metabolic abnormalities in patients with type 2 diabetes (T2D) increases the risk of cardiovascular disease and other comorbidities. This analysis compared the effects of tirzepatide (5, 10, and 15mg) and dulaglutide 0.75mg on the prevalence of metabolic abnormalities in Japanese patients with T2D. This was a post hoc analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled, parallel-group, phase 3 trial that compared the efficacy and safety of tirzepatide monotherapy (5, 10, and 15mg) to dulaglutide 0.75mg in Japanese patients with T2D. Thresholds for abnormalities were based on the Japanese criteria for metabolic syndrome. Proportions of participants meeting a composite endpoint (visceral fat accumulation measured by waist circumference plus two or more of dyslipidemia, hypertension, or hyperglycemia) or individual component thresholds were calculated at baseline and week 52 for the overall population and for baseline body mass index (BMI) subgroups (< 25, 25 to < 30, and ≥ 30kg/m2). Of 636 randomized participants, 431 (67.8%) met the composite endpoint at baseline, with similar findings observed across treatment arms. At week 52, the proportion of participants on treatment that met the composite endpoint was 31.7%, 23.0%, and 14.2% in the tirzepatide 5-, 10-, and 15-mg arms, respectively, and 56.5% in the dulaglutide arm (p < 0.001). A higher proportion met the composite endpoint at baseline in the BMI 25 to < 30 and ≥ 30kg/m2 subgroups (73.2-79.3%) compared with the < 25kg/m2 subgroup (45.3%), with reductions observed across all BMI subgroups treated with tirzepatide. The proportion of participants with individual metabolic abnormalities showed similar trends to those observed for the composite endpoint. Tirzepatide was consistently superior to dulaglutide across all assessments. Tirzepatide reduced the prevalence of multiple metabolic abnormalities, indicating tirzepatide may have metabolic benefit in Japanese patients with T2D. ClinicalTrials.gov, NCT03861052.

Echocardiographic Myocardial Work: A Novel Method to Assess Left Ventricular Function in Patients with Coronary Artery Disease and Diabetes Mellitus.

Myocardial ischemia caused by coronary artery disease (CAD) and the presence of metabolic abnormalities and microvascular impairments detected in patients with diabetes mellitus (DM) are a common cause of left ventricular (LV) dysfunction. Transthoracic echocardiography is the most-used, non-invasive imaging method for the assessment of myocardial contractility. The accurate evaluation of LV function is crucial for identifying patients who are at high risk or may have worse outcomes. Myocardial work (MW) is emerging as an alternative tool for the evaluation of LV systolic function, providing additional information on cardiac performance when compared to conventional parameters such as left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) because it incorporates deformation and load into its analysis. The potential of MW in various conditions is promising and it has gained increased attention. However, larger studies are necessary to further investigate its role and application before giving an answer to the question of whether it can have widespread implementation into clinical practice. The aim of this review is to summarize the actual knowledge of MW for the analysis of LV dysfunction caused by myocardial ischemia and hyperglycemia.

Healthy eating index and bone health markers in adults with metabolically healthy and unhealthy obese phenotypes

The Healthy Eating Index (HEI) estimates the diet quality, and low HEI scores are associated with adverse bone outcomes. However, the relationship between HEI scores and bone health in individuals who are obese but otherwise healthy or obese with comorbidities remains unclear. We aimed to evaluate the association of HEI scores with bone mineral density (BMD), bone regulating hormones and bone turnover markers in individuals with metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) phenotypes. This was a cross-sectional analysis of 122 adults who were overweight or obese. A questionnaire was completed to obtain demographic data. Body composition and BMD were assessed by a Dual Energy X-Ray Absorptiometry (DXA) exam. The HEI scores and dietary components were calculated using a 24-h dietary recall. Blood samples were collected for the analysis of serum 25-hydroxyvitamin D (s25OHD), total osteocalcin (OC), parathyroid hormone (PTH), and C-terminal telopeptide (CTx) concentrations. The MHO and MUO phenotypes were classified according to the absence or presence of metabolic abnormalities. The sample mean age was 37.91 ± 12.66 years, 50.8% were men, mean body mass index (BMI) was 30.01 ± 4.63 kg/m2, and 45.9% were classified as the MUO phenotype. The mean HEI scores were 54.42 ± 16.25 and 61.48% had low-diet quality. HEI scores were positively associated with s25OHD in the MUO phenotype group (β = 0.194, 95%CI = 0.038–0.350, p = 0.016). Certain dietary score components, such as fruits, seafood and plant protein, added sugars, whole grains, and fatty acids were also associated with bone health markers. However, HEI scores were not associated with BMD measures, neither with other bone regulating hormones and turnover markers. There was a positive association between HEI scores and s25OHD in adults who were overweight or obese with MUO phenotype. Additionally, the adequate consumption of specific food groups may benefit bone mass and metabolism. These results emphasize the importance of lifestyle interventions encouraging healthy eating habits to prevent s25OHD deficiency, poor bone health, and cardiometabolic complications.

Quality of life and psychosocial outcomes among children with metabolically healthy and unhealthy obesity.

Obesity and obesity-related morbidities are associated with poor psychosocial adjustment and health-related quality of life (HRQoL). This study aims to examine HRQoL and psychosocial outcomes in children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and the effects of familial health on these outcomes. Four hundred and six children with BMI for age ≥ 97th percentile were classified as having MHO and MUO based on the absence or presence of metabolic abnormalities. HRQoL and psychosocial outcomes were assessed using validated questionnaires such as PedsQL and DASS-21. There were no significant differences in HRQoL and psychosocial outcomes between children with MHO and children with MUO. Children with MUO and prior knowledge of existing metabolic conditions reported significantly lower total HRQoL (71.18 ± 17.42 vs. 75.34 ± 15.33), and higher depression (12.16 ± 11.80 vs. 8.95 ± 8.52) and stress (12.11 ± 8.21 vs. 10.04 ± 7.92) compared to children with MHO. Children with MUO who had fathers with metabolically unhealthy phenotype reported significantly lower total HRQoL (72.41 ± 15.67 vs. 76.82 ± 14.91) compared to children with MUO who had fathers with metabolically healthy phenotype. Prior knowledge of existing metabolic abnormalities was associated with poorer HRQoL and mental health in children with obesity. Paternal metabolic health status influenced HRQoL in children with MUO. First study that compared health-related quality of life (HRQoL) and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). No significant differences in HRQoL and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). Children with MUO who had prior knowledge of existing metabolic conditions reported lower HRQoL, higher depression and stress compared to children with MHO. Paternal metabolic health status was found to influence HRQoL in children with MUO. Mental health support intervention with paternal involvement should be provided for children with MUO.

Diagnostic ability using fatty liver and metabolic markers for metabolic‐associated fatty liver disease stratified by metabolic/glycemic abnormalities

Although several noninvasive predictive markers for fatty liver and metabolic markers have been used for fatty liver prediction, whether such markers can also predict metabolic-associated fatty liver disease (MAFLD) remains unclear. We aimed to examine the ability of existing fatty liver or metabolic markers to predict MAFLD. Participants in a high-volume center in Tokyo were classified into groups with and without MAFLD, based on the presence of metabolic abnormalities and fatty liver diagnosed through abdominal ultrasonography, between 2008 and 2018. The diagnostic abilities of three fatty liver markers: fatty liver index (FLI), hepatic steatosis index (HSI), and lipid accumulation product (LAP), and three common metabolic markers: waist-to-height ratio (WHR), body mass index (BMI), and waist circumference (WC), for predicting MAFLD, were evaluated. Analyses stratified by MAFLD subtypes were performed. Of 92,374 individuals, 19,392 (36.1%) had MAFLD. The diagnostic performances for MAFLD prediction, measured as c-statistics, for FLI, HSI, LAP, WHR, BMI, and WC were 0.906, 0.892, 0.878, 0.844, 0.877, and 0.878, respectively. Optimal cutoff values for diagnosing MAFLD for FLI, HSI, LAP, WHR, BMI, and WC were 20.3, 32.7, 20.0, 0.49, 22.9, and 82.1, respectively. Analyses stratified by MAFLD subtypes, based on BMI and metabolic/glycemic abnormalities, suggested that FLI and HSI had acceptable (c-statistics >0.700) diagnostic abilities throughout all the analyses. All six markers were excellent predictors of MAFLD in diagnosing among the general population, with FLI and HSI particularly useful among all sub-populations.

Comparison of anthropometric and physiological hemodynamic parameters in metabolic syndrome population

Background: Metabolic syndrome (MS) is a cluster of interrelated metabolic risk factors consisting of obesity, high blood pressure (BP), disturbance in glucose metabolism and dyslipidemia. It has been reported that obesity and incidence of cardiovascular disease (CVD) along with cardio-metabolic risk factors are associated with each other. Aim and Objectives: The aim of the study was to compare anthropometric parameters such as height, weight, body mass index (BMI), waist circumference (WC), and hemodynamic parameters such as systolic BP (SBP), diastolic BP (DBP), and pulse rate with the severity of MS. Materials and Methods: A total of 195 participants who volunteered with the signs of MS were divided into three groups based on the presence of metabolic abnormalities as Group I (with

Adiposity and cancer: a Mendelian randomization analysis in the UK biobank.

Observational and Mendelian randomization (MR) studies link obesity and cancer, but it remains unclear whether these depend upon related metabolic abnormalities. We used information from 321,472 participants in the UK biobank, including 30,561 cases of obesity-related cancer. We constructed three genetic instruments reflecting higher adiposity together with either "unfavourable" (82 SNPs), "favourable" (24 SNPs) or "neutral" metabolic profile (25 SNPs). We looked at associations with 14 types of cancer, previously suggested to be associated with obesity. All genetic instruments had a strong association with BMI (p < 1 × 10-300 for all). The instrument reflecting unfavourable adiposity was also associated with higher CRP, HbA1c and adverse lipid profile, while instrument reflecting metabolically favourable adiposity was associated with lower HbA1c and a favourable lipid profile. In MR-inverse-variance weighted analysis unfavourable adiposity was associated with an increased risk of non-hormonal cancers (OR = 1.22, 95% confidence interval [CI]:1.08, 1.38), but a lower risk of hormonal cancers (OR = 0.80, 95%CI: 0.72, 0.89). From individual cancers, MR analyses suggested causal increases in the risk of multiple myeloma (OR = 1.36, 95%CI: 1.09, 1.70) and endometrial cancer (OR = 1.77, 95%CI: 1.16, 2.68) by greater genetically instrumented unfavourable adiposity but lower risks of breast and prostate cancer (OR = 0.72, 95%CI: 0.61, 0.83 and OR = 0.81, 95%CI: 0.68, 0.97, respectively). Favourable or neutral adiposity were not associated with the odds of any individual cancer. Higher adiposity associated with a higher risk of non-hormonal cancer but a lower risk of some hormone related cancers. Presence of metabolic abnormalities might aggravate the adverse effects of higher adiposity on cancer. Further studies are warranted to investigate whether interventions on adverse metabolic health may help to alleviate obesity-related cancer risk.

Optimal cutoff values for anthropometric indices of obesity as discriminators of metabolic abnormalities in Korea: results from a Health Examinees study

BackgroundObesity is well known as a risk factor for cardiovascular disease. We aimed to determine the performance of and the optimal cutoff values for obesity indices to discriminate the presence of metabolic abnormalities as a primary risk factor for cardiovascular diseases in a Health Examinees study (HEXA).MethodsThe current study analyzed 134,195 participants with complete anthropometric and laboratory information in a Health Examinees study, consisting of the Korean population aged 40 to 69 years. The presence of metabolic abnormality was defined as having at least one of the following: hypertension, hyperglycemia, or dyslipidemia. The area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs) were calculated for body mass index, waist to hip ratio, waist to height ratio, waist circumference, and conicity index.ResultsThe AUC of metabolic abnormalities was the highest for waist-to-height ratio (AUC [95% CIs], 0.677 [0.672–0.683] among men; 0.691 [0.687–0.694] among women), and the lowest for the C index (0.616 [0.611–0.622] among men; 0.645 [0.641–0.649] among women) among both men and women. The optimal cutoff values were 24.3 kg/m2 for the body mass index, 0.887 for the waist-to-hip ratio, 0.499 for the waist-to-height ratio, 84.4 cm for waist circumference and 1.20 m3/2/kg1/2 for the conicity index among men, and 23.4 kg/m2 for the body mass index, 0.832 for the waist-to-hip ratio, 0.496 for the waist-to-height ratio, 77.0 cm for the waist circumference and 1.18 m3/2/kg1/2 for the conicity index among women.ConclusionThe waist-to-height ratio is the best index to discriminate metabolic abnormalities among middle-aged Koreans. The optimal cutoff of obesity indices is lower than the international guidelines for obesity. It would be appropriate to use the indices for abdominal obesity rather than general obesity and to consider a lower level of body mass index and waist circumference than the current guidelines to determine obesity-related health problems in Koreans.

Comparison of time to healing and major complications after surgical fixation of nondisplaced femoral neck stress fractures: A systematic review.

There is no recent literature review comparing outcomes of fixation methods for nondisplaced stress fractures of the femoral neck. A systematic review of the literature on operative fixation of femoral neck stress fractures was performed. Inclusion criteria consisted of diagnosis of nondisplaced femoral neck stress fractures, implants used for fixation, articles in English language or available English translation, all ages, and Level 1-5 evidence, documented time to healing, and incidence of complications. Statistical analysis was performed to compare outcomes. Eight studies with 13 subjects and 15 fractures undergoing operative fixation were included. Six fracture were compression sided, five were tension sided, and four were complete. Radiographic healing occurred on average at 32.7±36.3 weeks (range 8-121 weeks). Four subjects were noted to have a metabolic disturbance. Six subjects did not participate in vigorous exercise. There were no complications. There was no significant difference in radiographic healing time between: cannulated screws or SHS ± osteotomy (p=0.21); compression sided, tension sided, or complete fractures (p=0.41); ages (p=0.09); sex (p=0.09) or individuals with or without metabolic disturbances (p=0.92). There was no difference between use of cannulated screw fixation, SHS+osteotomy, and SHS alone based on the subject's age (p=0.27) or cannulated screw vs SHS ± osteotomy given subject's age (p=0.19) or sex (p=1.0). Time to full weight bearing (FWB) did not significantly differ between implants (p=0.22). However, >8 weeks restricted weight bearing had increased healing times (p=0.002). Time to healing was not dependent on subjects' sex or age, fracture location, implant choice, or presence of metabolic abnormality. No complications were reported. Time to full weight bearing was not dependent on implant choice. However, restricted weight bearing beyond 8 weeks can lead to prolonged healing times. Fixation should be safe, effective and promote early weight bearing and mobilization.

Dyslipidemia Fact Sheets in Korea 2020: an Analysis of Nationwide Population-based Data.

ObjectiveThe Korean Society of Lipid and Atherosclerosis (KSoLA) has published the Dyslipidemia Fact Sheets in Korea 2020 to provide an overview of magnitude and management status of dyslipidemia and their recent trends therein.MethodsThe Fact Sheets were based on the analyses of Korean adults aged 20 years or older of the 2007–2018 Korea National Health and Nutrition Examination Survey (KNHANES) and the 2002–2018 National Health Insurance Big Data (NHI-BD).ResultsBetween 2007 and 2018, the crude prevalence of hypercholesterolemia increased from 9.0% to 20.7%. During the same period, its management rate also improved yet remained unsatisfactory. In 2018, the prevalence of dyslipidemia was 45.6% in men and 31.3% in women, which increased with older age and presence of metabolic abnormalities. Indeed, the number of people diagnosed with dyslipidemia has increased nearly 8-fold from 1.5 million in 2002 to 11.6 million in 2018; alongside, the number of people receiving pharmacological treatment for dyslipidemia has also risen. Of the 7.7 million people treated for dyslipidemia in 2018, statin accounted for the majority (91.8%) of lipid-lowering drug prescriptions, followed by ezetimibe (14.6%), fibrate (8.5%), and omega-3 acid (5.9%). The most frequently used combination therapy was statin plus ezetimibe, accounting for 72% of dual therapy prescriptions.ConclusionDyslipidemia continues to impose a substantial disease burden in Korea. Both healthcare practitioners and patients need to actively adopt guideline-recommended lifestyle modification and pharmacological treatment for comprehensive, timely, and sustained management.

COMPARISON OF INSULIN RESISTANCE WITH THE SEVERITY OF METABOLIC SYNDROME

Objective: Insulin resistance (IR) means a reduced ability of insulin to stimulate glucose utilization. IR is related to cardiovascular disease (CVD) risk as the IR forms the basis for atherogenesis and acts as a major risk factor for atherosclerotic CVD.&#x0D; Methods: Total of 195 participants were recruited divided into three groups based on the presence of metabolic abnormalities as control Group I (with &lt;3 components of metabolic syndrome [MS]), MS group as Group II (with any 3 components of MS), and severe MS as Group III (with more than three components of MS).&#x0D; Results: Results showed that fasting blood sugar (FBS) and glycated hemoglobin showed a significant difference between the groups (p&lt;0.001), whereas fasting insulin and IR were higher in severe MS which showed statistically significant difference (p&lt;0.001) in comparison with control and MS group.&#x0D; Conclusion: IR is one of the principal factors for the development of MS and further threw light that the increase in the IR level proportionately increases the severity of MS.

Mortality of NAFLD According to the Body Composition and Presence of Metabolic Abnormalities.

Although nonalcoholic fatty liver disease (NAFLD) is associated with obesity, it can also occur in lean and metabolically normal individuals. Our aim was to determine the effect of different combinations of abdominal adiposity and overall adiposity on the mortality of NAFLD. The Third National Health and Nutrition Examination Survey with mortality data from the National Death Index were used. NAFLD was defined as steatosis without other liver diseases. Body composition was categorized according to waist circumference (WC) and body mass index (BMI). Obesity pattern was defined according to BMI (lean, overweight, and obese) and WC (normal and obese) using accepted definitions. The “metabolically abnormal” group had visceral obesity, insulin resistance, type 2 diabetes, hypertension, or hyperlipidemia. Of the 9,341 study individuals (47.9% male; 76.8% white), NAFLD was present in 3,140 (33.6%), of whom 0.6% had lean BMI and normal WC, and 1.7% had lean BMI and obese WC. The prevalence of metabolically normal NAFLD was 3.26% (95% confidence interval [CI]: 2.62%‐3.90%), with most of these subjects having lean BMI (79.2%). During an average follow‐up of 22.4 years, 24.1% of the subjects died from all causes. Among these deceased individuals, 41.7% had NAFLD at baseline. Causes of death were cardiovascular disease (24.8%), cancer‐related (24.3%), type 2 diabetes–related (4.4%), and liver‐related (1.7%). Individuals with NAFLD who were lean by BMI but obese by WC had higher risk of all‐cause mortality. Individuals with NAFLD with normal BMI but obese WC had a higher risk of cardiovascular mortality (hazard ratio 2.63 [95% CI: 1.15‐6.01]) as compared with overweight (by BMI) NAFLD with normal WC. Conclusion: The risk of mortality in NAFLD can be affected by the presence of visceral obesity, especially in the lean BMI group. These data have important management implications for patients with NAFLD.

Impact of metabolically healthy obesity on the risk of incident gastric cancer: a population-based cohort study

BackgroundThe risk of colon or breast cancer in metabolically healthy obese (MHO) were lower than that in metabolically abnormal obese (MAO). We hypothesized that the risk of incident gastric cancer in MHO is lower than that in MAO.MethodsThis historical cohort study included 19,685 Japanese individuals who received health-checkup programs from 2003 to 2016. Each subject was classified as metabolically healthy (MH) (no metabolic abnormalities) or metabolically abnormal (MA) (one or more metabolic abnormalities), according to four metabolic factors (hypertension, impaired fasting glucose, hypertriglyceridemia and low HDL-cholesterol). Obese (O) or non-obese (NO) was classified by a BMI cutoff of 25.0 kg/m2. Hazard ratios of metabolic phenotypes for incident gastric cancer were calculated by the Cox proportional hazard model with adjustments for age, sex, alcohol consumption, smoking and exercise.ResultsOver the median follow-up period of 5.5 (2.9–9.4) years, incident rate of gastric cancer was 0.65 per 1000 persons-years. Incident rate of MHNO, MHO, MANO and MAO were 0.33, 0.25, 0.80 and 1.21 per 1000 persons-years, respectively. Compared with MHNO, the adjusted hazard ratios for development of gastric cancer were 0.69 (95% CI 0.04–3.39, p = 0.723) in MHO, 1.16 (95% CI 0.63–2.12, p = 0.636) in MANO and 2.09 (95% CI 1.10–3.97, p = 0.024) in MAO.ConclusionsThis study shows that individuals with MAO, but not those with MHO, had an elevated risk for incident gastric cancer. Thus, we should focus more on the presence of metabolic abnormalities rather than obesity itself for incident gastric cancer.

Obesity without metabolic disorder and silent brain infarcts in aneurologically healthy population.

Obesity without metabolic disorder [Ob(+)MD(-)] is a unique subcategory of obesity where individuals are protected from the obesity-related complications. Although conflicting clinical outcomes have been reported, there has been no study of the effects of Ob(+)MD(-) on cerebrovascular disease. In this study, we evaluated the association between the Ob(+)MD(-) phenotype and silent brain infarcts (SBI) in a neurologically healthy population. We evaluated a consecutive series of healthy volunteers recruited between January 2006 and December 2013. MD(-) status was assessed using five clinical markers: blood pressure, triglycerides, high-density lipoprotein, fasting plasma glucose, and waist circumference. Obesity was defined when body mass index ≥ 25 kg/m2. SBI was defined as asymptomatic, well-defined lesions with a diameter ≥ 3 mm with the same signal characteristics as the cerebrospinal fluid on T1- or T2-weighted images. A total of 3165 subjects were assessed, and 262 (8%) SBI cases were identified. In multivariate analyses, non-obesity with metabolic disorder [Ob(-)MD(+)] (adjusted odds ratio [aOR] = 1.65, 95% confidence interval [CI] = 1.07-2.56, P = 0.025) and obesity with metabolic disorder [Ob(+)MD(+)] (aOR = 1.75, 95% CI = 1.12-2.75, P = 0.014) were closely associated with SBI after adjustment for confounders. Meanwhile, Ob(+)MD(-) did not show any significant association with SBI (aOR = 0.85, 95% CI = 0.20-3.72, P = 0.832). These findings may indicate that metabolic abnormality, irrespective of obesity status, is a main risk factor of SBI. When we compared SBI burdens between the four metabolic phenotypes, the Ob(+)MD(+) and Ob(-)MD(+) groups had higher rates of multiple lesions than the Ob(+)MD(-) and non-obesity without metabolic disorder groups. The presence of metabolic abnormality, and not obesity per se, is independently associated with the prevalence of SBI in a healthy population.

Presence of metabolic abnormalities in patients with acute myocardial infarction: at the onset and after recovery. A pilot study.

Presence of metabolic abnormalities in patients with acute myocardial infarction: at the onset and after recovery. A pilot study.

The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options

Although patients with cryptogenic cirrhosis have historically been considered as having "burnt-out" non-alcoholic steatohepatitis (NASH), some controversy remains. The aim of this study was to compare outcomes of patients with cryptogenic cirrhosis and NASH-related cirrhosis from a cohort with longitudinal follow-up data. Patients with cryptogenic cirrhosis or NASH cirrhosis were screened for a clinical trial. Patients with <5% hepatic steatosis regardless of other histologic features were considered to have cryptogenic cirrhosis. Clinico-laboratory data and adjudicated liver-related events (e.g. decompensation, qualification for transplantation, death) were available. A total of 247 patients with cirrhosis (55.3 ± 7.4 years, 37% male) were included; 144 had NASH cirrhosis and 103 had cryptogenic cirrhosis. During a median follow-up of 29 (IQR 21-33) months (max 45 months), 20.6% of patients had liver-related clinical events. Patients with NASH cirrhosis and cryptogenic cirrhosis were of a similar age and gender, as well as having a similar body mass index, PNPLA3 rs738409 genotype, and prevalence of diabetes (p >0.05). However, patients with cryptogenic cirrhosis had higher serum fibrosis markers and greater collagen content and α-smooth muscle actin expression on liver biopsy. Compared to cirrhotic patients with NASH, patients with cryptogenic cirrhosis experienced significantly shorter mean time to liver-related clinical events (12.0 vs. 19.4 months; p = 0.001) with a hazard ratio of 1.76 (95% CI 1.02-3.06). Populations with NASH and cryptogenic cirrhosis have similar demographics, but patients with cryptogenic cirrhosis have evidence of more active fibrosis and a higher risk of liver-related clinical events. Thus, we believe these patients belong to the same spectrum of disease, with cryptogenic cirrhosis representing a more advanced stage of fibrosis. Significant liver damage and cirrhosis of the liver may develop without a known cause - a liver disease referred to as cryptogenic cirrhosis. In this work we found that, in the presence of metabolic abnormalities, cryptogenic cirrhosis may actually be a part of the non-alcoholic fatty liver disease spectrum. Yet, it appears to be more progressive than typical non-alcoholic fatty liver disease, leading to advanced liver disease at a faster rate.

Importance of lipid-lipoprotein ratios as a diagnostic tool in metabolic syndrome population

Background: Metabolic syndrome (MS) is a constellation of diseases caused by several interconnected cardiometabolic risk factors such as obesity, hypertension, hyperglycemia, and dyslipidemia. Lipid-lipoprotein ratios can be considered as an alternative for identifying individuals with MS. Objectives: The objectives of this study were to compare the lipid profile and lipid-lipoprotein ratios of different groups formed based on the progression of the severity of MS. Materials and Methods: A total of 195 participants who volunteered with the signs of MS were divided into three groups based on the presence of metabolic abnormalities as Group I (with 3 components of MS - severe MS group). Results: Results showed that triglycerides (TG), ratio of TG-to-high-density lipoprotein, and total cholesterol (TC)-to-high-density lipoprotein ratio showed significant difference (P < 0.001) between the groups, whereas the results of high-density lipoprotein and lowdensity lipoprotein-to-high-density lipoprotein ratio were significantly more (P < 0.001) in severe MS in comparison with control and MS. TC showed significant difference (P = 0.004) in MS and severe MS when compared with that of control. Conclusion: Early identification and treatment of individuals with MS is very important to prevent debilitating effects associated with its development.

Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study).

BackgroundRecent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities.Methods1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC.ResultsMetabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10−6). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p<0.05). When we evaluated only body weight (without considering metabolic phenotypes), overweight or obese patients did not differ significantly from normal-weight patients in their IMT-CC (p = 0.077). However, obesity was a determinant of IMT-CC when compared to the composite group of normal weight and overweight patients (all not obese).ConclusionsIn coronary patients, a metabolically abnormal phenotype is associated with a greater IMT-CC, and may be linked to a higher risk of suffering new cardiovascular events. The protection conferred in the IMT-CC by the absence of metabolic abnormality may be blunted by the presence of obesity.Trial RegistrationClinicalTrials.gov NCT00924937

Stone management in children

Children constitute only a small number of the total patients with urolithiasis. Nevertheless, pediatric stone disease is an important health care problem because of its high recurrence rate. In recent years, the incidence of pediatric stone disease has increased several-fold, mostly owing to hypercalciuria and hypocitraturia. Chang Kit and colleagues’1 article highlights the pattern of nephrolithiasis in developed countries and depicts the major differences in presentation, predisposing factors and treatment options in children presenting with urinary stones. Children can present with a wide range of symptoms varying from flank pain and hematuria to nonspecific symptoms such as irritability and nausea. Ultrasonography and plain radiography play a role in diagnosis and follow-up. As shown by Chang Kit and colleagues, the most common diagnostic radiological methods used were abdominal ultrasonography (74%) and (or) abdominal plain film radiography (56%). Approaching pediatric urolithiasis requires a thorough metabolic and environmental evaluation of all patients on an individual basis, and as shown by Chang Kit and coworkers, 41% (28/69) had a metabolic abnormality. In addition, since there is a high recurrence rate, metabolic evaluation of every child with a urinary stone should be undertaken, medical treatment should be given when indicated and children should be followed closely to avoid stone recurrence. The medical treatment is based on the chemical composition of the stone and the biochemical abnormalities causing its formation; hence, chemical analysis of the stone, urine and blood is of paramount importance and should be done when the first stone is detected. The nonpharmacological means to address stone disease include high fluid intake and, frequently, modification of nutritional habits. Urine volume increases in parallel with body mass index, and medical therapeutic agents that increase urine citrate levels should be encouraged. Limiting salt in the diet and drinking plenty of water are the best ways to prevent the most common types of kidney stones or to slow their growth, but the ease in applying these dietary guidelines in children is not known. Furthermore, obstructive pathologies such as ureteropelvic junction obstruction have to be corrected concomitantly when present, and apparent metabolic abnormalities should also be treated adequately. The goal of medical treatment is not only to decrease recurrence but also to decrease the expansion of existing stones. It is thought that children have elastic ureters, allowing them to pass stones easily. In Chang Kit and colleagues’ study, 47% of patients spontaneously passed their stones even when they were as big as 11 mm. Nevertheless, more than one-half of the patients needed surgical intervention. With recent advances in technology, stone management has changed from an open surgical approach to less-invasive approaches such as extracorporeal shock wave lithotripsy and endoscopic techniques. In children, clearance of stones after extracorporeal shock wave lithotripsy especially in the presence of metabolic abnormality is necessary because residual fragments are clinically significant in children and increase the chance of adverse clinical outcomes.2 Thus these patients, particularly those with identifiable predisposing disorders, require close follow-up. Traditionally, upper urinary tract calculi that are too large to treat with extracorporeal shock wave lithotripsy are most commonly cleared with percutaneous endoscopic techniques. Recently, improved ureteroscopic access to stones throughout the pediatric urinary tract and stone-free rates that are comparable to the adult population have led to the adoption of ureteroscopy as first-line therapy in children at our institution.3 In a select group of patients who are poor candidates for percutaneous nephrostolithotomy, retrograde endoscopic lithotripsy is becoming an attractive option. Thus with miniaturization and advances in technology, large and complex upper urinary tract calculi can be addressed safely and efficiently with retrograde endoscopic techniques. For instance, ureteroscopy achieves reasonable results with minimal complications in pediatric patients with renal pelvic calculi. On the other hand, polar stones require multiple sessions for complete clearance, and staghorn calculi may not be amenable to ureteroscopy. In their article, Chang Kit and colleagues do not report the number of procedures performed that lead to full success for each surgical approach, nor do they report the complications that occurred when they approached the patients surgically.

Uncertainty Remains in Women with PCOS Regarding the Increased Incidence of Cardiovascular Disease Later in Life, Despite the Indisputable Presence of Multiple Cardiovascular Risk Factors at a Young Age

It is increasingly recognized that crucial gender differences exist in heart disease, with men being at higher cardiovascular (CV) risk, especially at a young age. It is generally accepted that women often suffer most from the burden of CV disease after menopause (1), which has been attributed to a safer hormonal environment before menopause. However, as elegantly suggested recently, in women the CV risk increases exponentially with age with no specific increase after natural menopause (2). This further emphasizes the need for the early recognition of risk factors and for developing secondary prevention strategies in women. It has recently become apparent that multiple disease conditions in obstetrics and gynecology [such as pregnancyinduced hypertension (PIH), polycystic ovary syndrome (PCOS), but also hypothalamic amenorrhea, primary ovarian insufficiency, and early menopause] are associated with increased CV risk. Moreover, increased CV disease has been convincingly demonstrated for both PIH and primary ovarian insufficiency (3, 4). Much controversy remains regarding the many clinical issues associated with the enigmatic PCOS. Ongoing debate as to whether hyperandrogenemia should remain the hallmark for diagnosis has rendered the 2003 Rotterdam consensus criteria for PCOS diagnosis one of the most frequently cited papers in the (short) history of clinical reproductive medicine (5). Until recently, interest has focused mainly on infertility treatment of anovulatory PCOS (6). In more recent years, however, overall attention has shifted toward the more frequent occurrence of pregnancy complications in PCOS, such as gestational diabetes and PIH (7). Moreover, a wealth of literature—mostly published in this journal—has established the presence of metabolic abnormalities in the daughters of women with PCOS (8–10), with increasing claims for the need to treat such adolescent girls with multiple drugs such as flutamide, metformin, and pioglitazone (11). The diagnosis of the notoriously heterogeneous PCOS is based on three features, i.e. menstrual cycle abnormalities, polycystic ovaries, and hyperandrogenemia. In addition, many of these women are obese and present with impaired glucose tolerance (even in lean PCOS). Numerous studies have now established beyond any doubt that women with PCOS exhibit multiple CV risk factors such as impaired glucose tolerance, type 2 diabetes and the metabolic syndrome (12), dyslipidemia (13), and other CV risk markers such as C-reactive protein, homocysteine, TNF, and many others (14). Relatively few and small sample size studies have suggested subclinical arterial disease in women with PCOS, such as abnormal carotid intima media thickness or coronary artery calcification (15). The metabolic syndrome is associated with a 2-fold increase in CV disease and a 1.5-fold higher all-cause mortality, as demonstrated by a recent systematic review involving 87 studies and a total of almost 1 million patients (16). Based on the above-mentioned observations, firm position statements have been generated by the Androgen Excess Society—again published in JCEM—recommending that every woman with PCOS should undergo a 2-h