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1.  Reviewer acknowledgement 2014 
Contributing reviewers
The Editors of Diabetology & Metabolic Syndrome would like to thank all of our reviewers, both external and Editorial Board Members, who have contributed to the journal in Volume 6 (2014) and whose valuable support is fundamental to the success of the journal.
PMCID: PMC4335699
2.  Serum prolidase activity is associated with non-diabetic metabolic syndrome 
The aim of this study was to determine the role of serum prolidase activity and the possible association with oxidative stress parameters in non-diabetic metabolic syndrome.
30 obese patients without metabolic syndrome (MetS), 34 non-diabetic obese patients with MetS, and 23 volunteer control subjects were enrolled in the study. Fasting plasma glucose (FPG), plasma glucose following 75 g glucose administration, high-density lipoprotein- cholesterol (HDL-C), high-density lipoprotein- cholesterol (LDL-C), total cholesterol, triglyceride (TG), total antioxidant status (TAS), total oxidative status (TOS), oxidative stress index (OSI), and prolidase activities of all subjects were analyzed.
Prolidase levels was significantly higher in MetS group compared to both obese and control groups (p < 0.001 and p < 0.05 respectively). Prolidase was also higher in the obese group than in the control group (p < 0.05). Prolidase was negatively correlated with TAS and HDL-C (r = −0,362, p < 0.001; r = −0.320, p < 0.01, respectively) and positively correlated with BMI, weight, waist-c, SBP, DBP, TG, TC, LDL-C.
Prolidase activity may have a role in the pathogenesis of metabolic syndrome.
PMCID: PMC4276100  PMID: 25540672
Metabolic syndrome; Non-diabetic; Obesity; Prolidase
3.  The relationship between glycemic variability and diabetic peripheral neuropathy in type 2 diabetes with well-controlled HbA1c 
Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes. Glycemic variability could be an independent risk factor for diabetes complications in addition to average glucose. Type 2 diabetes with well-controlled glycosylated hemoglobin A1c (HbA1c) may have different terms of glycemic variability and vascular complication consequences. The aim of the study is to investigate the relationship between glycemic variability and DPN in type 2 diabetes with well-controlled HbA1c (HbA1c < 7.0%).
45 type 2 diabetes with well-controlled HbA1c(HbA1c < 7.0%) and with DPN (DM/DPN group) were recruited in the study, and 45 type 2 diabetes with well-controlled HbA1c and without DPN (DM/–DPN group) were set as controls. The two groups were also matched for age and diabetic duration. Blood pressure, body mass index(BMI), insulin sensitivity index (Matsuda index, ISI), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), and low density lipoprotein cholesterol (LDLC) were tested in the two groups. And all patients were monitored using the continuous glucose monitoring (CGM) system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SDBG), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE).
The DM/DPN group had a greater SDBG, MODD and MAGE, when compared to the DM/–DPN group (p < 0.05). BMI, TC, and LDLC of DM/DPN group were lower than those of DM/–DPN group (p < 0.05). The patients with hypoglycemia were comparable between the two groups (p > 0.05). Univariate analysis showed DPN was closely associated with BMI (OR 0.82, CI 0.72–0.94, p = 0.005), TC (OR 0.63, CI 0.42–0.93, p = 0.02), LDLC (OR 0.4, CI 0.20–0.80, p = 0.009), SDBG (OR 2.95, CI 1.55–5.61, p = 0.001), MODD (OR 4.38, CI 1.48–12.93, p = 0.008), MAGE (OR 2.18, CI 1.47–3.24, p < 0.001). Multivariate logistic regression analysis showed that MAGE (OR 2.05, CI 1.36–3.09, p = 0.001) and BMI (OR 0.85, CI 0.73–0.99, p = 0.033) were significantly correlating with DPN. Glycemic variability, evaluated by MAGE, was the most significantly independent risk factor for DPN.
There was a close relationship between glycemic variability evaluated by MAGE and DPN in type 2 diabetes with well-controlled HbA1c.
PMCID: PMC4272789  PMID: 25530811
Glycemic variability; Continuous glucose monitoring; Diabetic peripheral neuropathy; Type 2 diabetes
4.  Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome 
The purpose of this research was to study the gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), vascular endothelial growth factor A (VEGF-A) and adiponectin (AdipoQ) genes in the visceral (omental, mesenteric) and subcutaneous adipose tissue depots in metabolic syndrome (MS).
We studied 23 women with MS, with a mean age of 50.7 ± 4.5 years and mean body mass index (BMI) of 45.6 ± 9.8 kg/m2. The control group included 10 women, with a mean age of 40.6 ± 8.7 years and normal BMI (22.3 ± 3.7 kg/m2). The gene expression levels in the omental (OAT), mesenteric (MAT) and subcutaneous (SAT) adipose tissues were assessed by quantitative real-time PCR.
Increased gene expression levels of IL-6 and TNF-α were detected in MAT in patients with MS, compared with the control group (p < 0.05 and p < 0.005, respectively). Significant positive correlations were observed between IL-6 mRNA expression levels in OAT and the content of CD14 + cells in the peripheral blood (r = 0.55, p < 0.05), as well as between NF-κB and VEGF-A mRNA levels in OAT (r = 0.43, p < 0.05) in patients with MS. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group (p < 0.05). In addition, there were inverse correlations between AdipoQ gene levels in MAT and serum CRP levels (r = −0.63, p < 0.05), as well as between AdipoQ gene levels in MAT and serum IL-6 levels (r = −0.46, p < 0.05).
These data demonstrate that proinflammatory gene expression of MAT in women with MS was increased compared with the control group. The AdipoQ gene expression levels in OAT were significantly decreased in women with MS compared with the control group.
PMCID: PMC4267145  PMID: 25516772
Metabolic syndrome; Adipose tissue; Inflammation; Obesity; Adipokine; Gene expression
5.  Differential association between obesity and coronary artery disease according to the presence of diabetes in a Korean population 
Coronary artery disease (CAD) is a major cardiovascular complication in diabetic patients. Despite the significant association between obesity and diabetes, the majority of the diabetic subjects are not obese in an Asian population. This study evaluated the association between obesity and coronary artery disease (CAD) according to the diabetes status in a Korean population.
The association between obesity and CAD using the parameters of any plaque, obstructive plaque, and coronary artery calcium score (CACS) >100 according to the presence of diabetes was evaluated in 7,234 Korean adults who underwent multi-detector computed tomography for general health evaluations. Obesity was defined as a body mass index (BMI) ≥25 kg/m2.
The prevalence of obesity was significantly higher in diabetic subjects than in non-diabetic subjects, but the majority of the diabetic subjects were non-obese (48% vs. 37%, p <0.001). The incidence of any plaque (58% vs. 29%), obstructive plaque (20% vs. 6%), and CACS >100 (20% vs. 6%) were significantly higher in diabetic patients than in non-diabetic subjects (p <0.001, respectively). Incidence of any plaque (33% vs. 26%, p <0.001), obstructive plaque (7% vs. 6%, p = 0.014), and CACS >100 (8% vs. 6%, p = 0.002) was significantly higher in non-diabetic subjects with obesity than in those without obesity, but the incidence of all coronary parameters was not different in diabetic subjects according to the obesity status. After adjusting for confounding risk factors including age, gender, hypertension, dyslipidemia, current smoking, and mild renal dysfunction, obesity was independently associated with increased risks of any plaque (OR 1.14) and CACS >100 (OR 1.31) only in non-diabetic subjects (p <0.05, respectively). Multiple logistic regression models revealed that diabetes was independently associated with all coronary parameters.
Despite a significantly higher prevalence of obesity in diabetic subjects than in non-diabetic subjects, obesity is associated with the presence of any plaque and severe coronary calcification only in subjects without established diabetes among Korean population.
PMCID: PMC4271324  PMID: 25530810
Obesity; Diabetes; Coronary artery disease; Cardiac computed tomographic angiography
6.  Circulating levels of irisin in middle-aged first-degree relatives of type 2 diabetes mellitus — correlation with pancreatic β-cell function 
Irisin is a novel myokine secreted in response to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) activation through exercise. The first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients bear a lifetime risk for developing T2DM, especially after 40 years old. However, the circulating irisin levels in middle-aged FDRs of T2DM is unclear. We therefore investigated the association between circulating irisin and pancreatic β-cell function in normal-glucose-tolerance (NGT) subjects.
In this cross-sectional study, we recruited 412 supposed healthy subjects aged 40-60 who were FDRs of T2DM patients but without previous diagnosis of T2DM. Of the 412 individuals, 254 had NGT and 60 were newly diagnosed T2DM based on the results of a 75 g oral glucose tolerance test (OGTT- World Health Organization diagnostic criteria). We measured irisin in the newly diagnosed T2DM group (n = 60) and in an age- and sex-matched NGT subgroups (n = 62). Serum irisin was quantified by ELISA, and its association with metabolic parameters was analysed by Pearson’s correlation and multiple linear regression analyses.
There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients and the NGT control group. Circulating irisin was correlated with haemoglobin A1c (r = 0.202, p = 0.026) and estimated glomerular filtration rate (r = 0.239, p = 0.010). Multiple linear regression revealed that only homeostasis model assessment-β (HOMA-β) was associated with irisin in NGT subjects after adjusting for confounding factors. However, similar analysis in T2DM did not reveal a significant association between circulating irisin and metabolic parameters.
There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients and the NGT controls. Serum irisin level was closely related to HOMA-β in NGT, suggesting that irisin may play a crucial role in pancreatic β-cell function.
PMCID: PMC4271516  PMID: 25530809
Type 2 diabetes mellitus; First-degree relatives; Irisin; Pancreatic β-cell
7.  Influence of acute hyperlipidemia to adipocyte-derived hormones in lean normotensive and subjects with metabolic syndrome 
Adipocyte-derived factors and regulators likely contribute to the metabolic syndrome (MetS) in patients with central obesity. This study was undertaken to assess the contribution of leptin, adiponectin, and acylation stimulating protein (ASP-C3ades/ARG) to hemodynamic (blood pressure [BP]) and metabolic (insulin, glucose, lipids) features of MetS.
In this study, leptin, adiponectin, and C3ades/ARG were measured at baseline and in response to an infusion of Intralipid® and heparin in 12 lean healthy controls and 12 patients with MetS.
Baseline plasma leptin (27.6 ± 6.2 vs. 10.9 ± 3.8 ng/mL, p < 0.01) and plasma C3ades/ARG (273 ± 79 vs 198 ± 57 mg/dL, p < 0.05) were higher in the MetS than control group, whereas baseline plasma adiponectin was higher in the control than MetS group (9.9 ± 1.9 vs. 5.4 ± 0.6 g/mL). Plasma leptin correlated with body mass index (BMI), systolic and diastolic BP (r = 0.53-0.77, p < 0.01). Conversely, adiponectin correlated inversely with insulin, glucose, waist circumference, and insulin sensitivity (r = 0.48-0.51, p ≤ 0.02). Plasma triglycerides increased similarly in MetS and control groups after 4-hours of Intralipid and heparin. C3ades/ARG increased only in lean volunteers. The decrease in triglycerides 1-hour post-infusion was lower in the MetS than control group (-116 ± 33 vs. -282 ± 81 mg/dL, p = 0.01) and correlated inversely with the change in C3ades/ARG.
These data suggest that leptin is more closely associated with hemodynamic (BP) aspects of MetS, whereas adiponectin and C3ades/ARG are more closely associated with metabolic components.
PMCID: PMC4265446  PMID: 25506401
Intralipid® and heparin; Adiponectin; Leptin; ASP/C3adesARG; Lean normotensives; Metabolic syndrome subjects
8.  Predictors for pregnancy outcomes in Romanian women with Type 1 Diabetes Mellitus: a prospective study 
Type 1 diabetes mellitus in pregnant women is associated with an increased risk of congenital malformations, obstetric complications, neonatal morbidity, and mortality. Our aim was to evaluate which factors from the first trimester of pregnancy have a significant impact on the pregnancy outcomes of women with type 1 diabetes.
We included 94 pregnant women with type 1 diabetes in this study. In these patients, we analyzed the influence of several diabetes-related parameters on the pregnancy outcome. We compared the parameters between two cohorts: those with successful pregnancies and those with adverse pregnancy outcomes, defined as spontaneous abortion or congenital malformations. The influence of several factors on the pregnancy outcome was assessed using multivariate and univariate logistic regressions.
The prevalence of adverse pregnancy outcomes was 28.7%, and was associated with poorer glycemic control (p <0.001), lower frequency of daily self-monitoring tests (p <0.001), smoking status (p <0.001), alcohol consumption (p <0.001), increased prevalence of chronic complications of diabetes, and the presence of ketosis. However, the adverse outcomes were not significantly associated with age, duration of diabetes, presence of thyroid disease, or body mass index. Furthermore, planned pregnancy was found to be a significant protective factor (odds ratio, 0.15; p <0.001).
These results indicate that by carefully planning the pregnancy, ensuring optimal glycemic control, and eliminating habitual risk factors, the fetal risk in pregnancies among women with type 1 diabetes may decrease to a value similar to that noted in women without diabetes.
PMCID: PMC4247610  PMID: 25435920
Pregnancy outcomes; Type 1 diabetes mellitus; Glycemic control
9.  The cost of type 2 diabetes in Brazil: evaluation of a diabetes care center in the city of São Paulo, Brazil 
The worldwide increase of diabetes, a long duration, slow progression disease, impacts health care costs. The aim of this study was to estimate, from the society’s perspective, the annual cost per patient with Type 2 Diabetes (T2DM) at a specialized, outpatient center in the city of São Paulo, capital of São Paulo state, Brazil.
Data from 209 patients were collected during the years 2009 and 2010 in a São Paulo diabetes care center which is part of the tertiary sector of SUS, Brazil’s National Health Care System. Data were collected by means of interviews and reviews of medical charts, and the quality of life was appraised using the SF36-v2 questionnaire. Direct medical costs were divided in five categories: 1) medication; 2) laboratory tests; 3) hospitalizations and procedures; 4) reactive strips for capillary blood glucose monitoring; and 5) medical consultations. Direct non-medical costs referred to transportation of patient and companion for treatment. Indirect costs included early retirements, sick leave and absenteeism in the workplace. Statistical analysis of the data was performed by the SPSS software, version 17.0.
Our sample comprised 122 women (58%) and 87 men (42%), with mean age of 63 years and average diabetes duration of 13 years. The mean annual cost was US$ 1,844 per patient, out of which US$ 1,012 corresponded to direct costs (55%) and US$ 831 to indirect costs (45%). From the direct medical costs, medications accounted for the greatest proportion (42%), followed by reactive strips (27%), hospitalizations and procedures (14%), laboratory tests and image examinations (7%), as well as medical consultations (4%). Non-medical costs (transportation) corresponded to 7% of the total direct costs. Besides, the results indicated that men have better quality of life than women.
This study demonstrated a high T2DM cost in Brazil, considering the governmental per capita expenses in health care, which accounted for US$ 466 in 2010 (World Health Statistics 2013 96-104 2013). Taking into account the high prevalence of the disease (IDF Diabetes Atlas. 5th edition. 29-48 2012), this survey recommends the enforcement of policies for the prevention of diabetes and its complications, and urges for better allocation of healthcare resources.
PMCID: PMC4232724  PMID: 25400703
Type 2 diabetes; Disease cost; Brazil; Outpatient
10.  The prevalence of the metabolically healthy obese phenotype in an aging population and its association with subclinical cardiovascular disease: The Brazilian study on healthy aging 
Current literature has elucidated a new phenotype, metabolically healthy obese (MHO), with risks of cardiovascular disease similar to that of normal weight individuals. Few studies have examined the MHO phenotype in an aging population, especially in association with subclinical CVD.
Research design and methods
This cross sectional study population consisted of 208 octogenarians and older. Anthropometrics, biochemical, and radiological parameters were measured to assess obesity, metabolic health (assessed by the National Cholesterol Education Program –Adult Treatment Panel (NCEP-ATP III) criteria), and subclinical measures of CVD.
The prevalence of MHO was 13.5% (N = 28). No significant association with MHO was noted for age, coronary artery calcium score, cIMT, or hs-CRP > 3 mg/dl (p = NS).
Our results suggest that the MHO phenotype exists in the elderly; however, subclinical CVD measures were not different in sub-group analysis suggesting traditional metabolic risk factor algorithms may not be accurate in the very elderly.
PMCID: PMC4236419  PMID: 25411583
Obesity; Aging; Metabolic Syndrome; Subclinical CVD
11.  The relationship between epicardial fat thickness and gestational diabetes mellitus 
Gestational diabetes mellitus (GDM) is associated with cardiovascular diseases; however, the relationship between epicardial fat thickness (EFT) and GDM remains unclear. The present study evaluates and compares EFT using transthoracic echocardiography in pregnant women with GDM.
Materials and methods
This cross-sectional study included 129 pregnant women in the third trimester: 65 with GDM (GDM group) and 64 with uncomplicated pregnancies (control group). As defined by the World Health Organization, the diagnosis of GDM was based on an abnormal 2-h oral glucose tolerance test (OGTT) results. We used echocardiography to measure EFT in blood samples for all the participants.
The postprandial blood glucose level was significantly higher in the GDM group than in the control group (P < 0.001). There were no significant differences in BMI, heart rate, systolic and diastolic blood pressure or lipid parameters between the groups. In the GDM group, isovolumic relaxation time (IVRT) parameters were significantly higher than in the control group. EFT was significantly higher in the GDM group (P < 0.001) and was correlated with postprandial glucose, BMI, age, and heart rate in both the groups. Only postprandial glucose and BMI remained significantly associated with EFT after multiple stepwise regression analysis.
Echocardiographically measured EFT was significantly higher in the patients with GDM. The findings show that EFT was strongly correlated with postprandial glucose.
PMCID: PMC4232611  PMID: 25400702
Atherosclerosis; Diabetes mellitus; Transthoracic echocardiography
12.  Supplementary use of HbA1c as hyperglycemic criterion to detect metabolic syndrome 
Metabolic syndrome (MetS) refers to a cluster of cardiovascular risk factors including hyperglycemia, dyslipidemia, abdominal obesity and hypertension. An effective detection of MetS not only reflects the prediction risk of diabetes mellitus and cardiovascular diseases but also helps to plan for management strategy which could reduce the healthcare burden of the society. This study aimed to compare the use of hemoglobin A1c (HbA1c) to fasting plasma glucose (FPG) as the hyperglycemic component in MetS diagnosis.
Waist circumference, blood pressure, blood triglyceride, high-density lipoprotein (HDL)-cholesterol, FPG, and HbA1c were examined in 120 Hong Kong Chinese adults with MetS and 120 without MetS. After reviewing the subject basal characteristics, 11 of them were found with undiagnosed diabetes (FPG ≧7.0 mmol/L) and were excluded for further analysis.
The most prevalent MetS components among the included subjects were elevated systolic blood pressure and central obesity. Significant correlation relationships existed between FPG and HbA1c in both subject pools diagnosed with and without MetS (p < 0.001). The diagnostic rate of MetS using HbA1c was compared to FPG by the receiver operating characteristics (ROC) analysis which suggested an area under curve of 0.807 (95% CI: 0.727 to 0.887). The agreement was 90.7% in MetS-positive group with increased FPG as one of the criterion co-existed with elevated HbA1c. If including HbA1c as an additional criterion to FPG in the MetS diagnosis, 30 more participants in MetS-negative group would be MetS-positive leading to an increase in detection rate. Furthermore, 47 subjects (38 from MetS-positive group and 9 from MetS-negative group) were found having HbA1c ≧6.5%, who would have been diagnosed with diabetes based on the diagnostic criteria implemented by the Expert Group in 2009.
These findings suggest that HbA1c enhances the detection of hyperglycemia for the diagnosis of MetS.
PMCID: PMC4232661  PMID: 25400701
13.  Muscle glycogen metabolism changes in rats fed early postnatal a fructose-rich diet after maternal protein malnutrition: effects of acute physical exercise at the maximal lactate steady-state intensity 
The objective was to evaluate the muscle glucose metabolism in rats fed a fructose-rich diet after fetal protein malnutrition, at rest and after acute physical exercise at maximal lactate steady-state intensity.
The male offspring born of mothers fed on a balanced or low-protein diet were split in four groups until 60 days: Balanced (B): balanced diet during the whole period; Balanced/Fructose (BF): balanced diet in utero and fructose-rich diet after birth; Low protein/Balanced (LB): low-protein diet in utero and balanced diet after birth; Low protein/Fructose (LF): low protein diet in utero and fructose-rich diet after birth.
Acute physical exercise reduced the muscle glycogen concentrations in all groups, although the LF group showed higher concentrations at rest. There was no difference among the groups in the glucose uptake and oxidation rates in the isolated soleus muscle neither at rest nor after acute exercise. However, glycogen synthesis was higher in the LF muscle than in the others at rest. Acute physical exercise increased glycogen synthesis in all groups, and the LF group showed the highest values.
The fructose-rich diet administered in rats after fetal protein malnutrition alters muscle glycogen concentrations and glycogen synthesis in the rest and after acute exercise at maximal lactate steady-state intensity.
PMCID: PMC4232698  PMID: 25400700
14.  Sex-based disparities in cardioprotective medication use in adults with diabetes 
The identification of sex-based disparities in the use of effective medications in high-risk populations can lead to interventions to minimize disparities in health outcomes. The objective of this study was to determine sex-specific rates of cardioprotective medication use in a large population-level administrative-health database from a universal-payer environment.
Research design and methods
This observational, population-based cohort study used provincial administrative data to compare the utilization of cardioprotective medications between women and men in the first year following a diabetes diagnosis. Competing risks regression was used to calculate crude and adjusted sub-hazard ratios for time-to-first angiotensin-converting-enzyme inhibitor, angiotensin receptor blocker, or statin dispensations.
There were 15,120 (45.4%) women and 18,174 (54.6%) men with diabetes in the study cohort. Overall cardioprotective medication use was low for both primary and secondary prevention for both women and men. In the year following a diabetes diagnosis, women were less likely to use a statin relative to men (adjusted sub-hazard ratio [aSHR] 0.90, 95% confidence interval [CI] 0.85 to 0.96), angiotensin-converting-enzyme inhibitors (aSHR 0.90, 95% CI 0.86 to 0.94), or any cardioprotective medication (aSHR 0.93, 95% CI 0.90 to 0.97).
Cardioprotective medication use was not optimal in women or men. We also identified a health care gap with cardioprotective medication use being lower in women with diabetes compared to men. Closing this gap has the potential to reduce the impact of cardiovascular disease in women with diabetes.
Electronic supplementary material
The online version of this article (doi:10.1186/1758-5996-6-117) contains supplementary material, which is available to authorized users.
PMCID: PMC4240896  PMID: 25419242
15.  Synergistic effects of neck circumference and metabolic risk factors on insulin resistance: the Cardiometabolic Risk in Chinese (CRC) study 
Recent studies have associated neck circumference (NC) with insulin resistance (IR). We examined whether such relation was modified by other metabolic risk factors.
The study samples were from a community-based health examination survey in central China. A total of 2588 apparently healthy Chinese men and women were included.
Plasma levels of total cholesterol (TC), HDL-C, uric acid (UA) and diastolic blood pressure (DBP) were independently associated with NC after adjusted for age, sex, body mass index (BMI), waist circumference (WC) and hip circumference (HC) (P = 0.009, 0.001, 0.015 and 0.015, respectively). We observed significant interactions of NC with triglyceride (TG) and UA (all the p for interaction = 0.001) in relation to HOMA-IR. It appeared that the associations between NC and HOMA-IR were more evident in those with higher UA or TG level.
Our data indicate that in apparently healthy Chinese adults, there were synergistic effects of UA, TG and neck circumference on insulin resistance.
PMCID: PMC4232709  PMID: 25400699
Insulin resistance; Neck circumference; Uric acid; Triglyceride; Synergistic effects
16.  Correlation between reduction of superior interventricular groove epicardial fat thickness and improvement of insulin resistance after weight loss in obese men 
It has been recognized that reduction of abdominal visceral fat and subcutaneous fat are associated with improvement in insulin-resistance (IR) after weight loss. However, few studies have investigated the correlation of reduction in epicardial adipose tissue (EAT) with improvement of IR index after weight loss in obese non-diabetic men with metabolic syndrome (MetS).
Methods and results
We prospectively enrolled 32 non-diabetic men with MetS for a 3-month weight reduction program mainly by diet control and exercise. Magnetic resonance imaging (MRI) examinations were used to measure EAT, subcutaneous fat, and abdominal visceral fat. Anthropometric parameters, oral glucose tolerance test (OGTT), and serum adipokines were assessed before and after the weight loss program. After a 3-month weight loss program, 27 obese MetS men had significant weight loss >5% (97 ± 14 to 87 ± 14 kg, with a 10.7 % decrease, p < 0.001). Multivariate analysis revealed that the decrement ratio of superior interventricular groove (SIVG) EAT thickness (r = 0.322, p = 0.044) and serum leptin (r = 0.626, p < 0.001) significantly correlated with the percentage improvements of fasting HOMA-IR index. Furthermore, the decrement ratio of SIVG EAT thickness (r = −0.370, p = 0.017) and decrement ratio of subcutaneous fat area (r = −0.673, p = 0.006) were significantly correlated with improvement of OGTT-derived Matsuda insulin-sensitivity index.
The decrement ratio of SIVG EAT correlated with improvement of both HOMA-IR and OGTT-derived Matsuda insulin-sensitivity indexes after weight loss in obese non-diabetic men with MetS.
Clinical trial registration
(Multi-faceted Evaluations Following Weight Reduction in Subjects with Metabolic Syndrome NCT 01065753 on Feb 8, 2010).
PMCID: PMC4223841  PMID: 25383099
Epicardial adipose tissue; Insulin resistance; Leptin; Matsuda index; Metabolic syndrome; Obesity
17.  Serum ferritin levels and the development of metabolic syndrome and its components: a 6.5-year follow-up study 
The aim of this study was to investigate the relationship between changes in serum ferritin concentrations and the development of metabolic syndrome (MetS) and its components over a 6.5 year follow-up period in Finnish adults.
Adults born in Pieksämäki, Finland, in 1942, 1947, 1952, 1957, and 1962 (n = 1294) were invited to health checkups between 1997 and 1998 and 2003 and 2004. All of the required variables for both checkups were available from 691 (53%) subjects (289 men and 402 women). MetS was defined by the National Cholesterol Education Program criteria.
During the 6.5-year follow-up period, 122 (18%) subjects developed incident cases of MetS. Increases in serum ferritin levels were significantly higher in both women and men with incident MetS compared with women and men without MetS (p = 0.04, p = 0.03). Also, serum ferritin levels increased significantly less in women in whom the criteria for MetS resolved during the follow-up period (p = 0.01). Increases in serum ferritin levels were significantly lower in women in whom the glucose criterion for MetS resolved, and higher in women for whom the waist criterion developed (p = 0.01 and p <0.001, respectively). Serum ferritin levels decreased significantly more in men in whom the triglyceride criterion for MetS resolved during the follow-up period (p = 0.01). There was a clear and significant correlation between change in serum ferritin level and change in waist circumference both in men and women (p <0.001, p <0.01). In addition, correlations between change in serum ferritin level and change in plasma triglyceride as well as glucose levels were strongly positive in men (p <0.001). There was negative correlation between change in serum ferritin and plasma high density cholesterol level both in men and women.
Increases in serum ferritin over a 6,5 year period are associated with development of MetS in both men and women. Whereas, lower increases in serum ferritin over the same timeframe are associated with resolution of hypertriglyceridemia in men and hyperglycemia in women. Increases in waist circumference was positively correlated with increases in serum ferritin in both men and women.
PMCID: PMC4219011  PMID: 25371712
Metabolic syndrome; Ferritin; Obesity
18.  Fish consumption and its possible preventive role on the development and prevalence of metabolic syndrome - a systematic review 
Metabolic syndrome (MetS) has a huge impact on public health, and today lifestyle interventions remain the primary mode for MetS therapy. It is therefore important to elucidate the possible preventive effects of diet and foods, and their MetS-related health implications. To examine how fish consumption affects the development and prevalence of MetS, we systematically reviewed cross-sectional, prospective cohort, and intervention studies conducted among adults (humans) and, reporting consumption of fish or seafood as being related to MetS (prevalence or incidence), where MetS was defined via an established definition. The literature search in PubMed identified 502 citations, and after screening, 49 full-text articles were retrieved and assessed for eligibility. After excluding duplicates and those not meeting the inclusion criteria, seven studies from Croatia, Finland, France, Iceland, Iran, Korea, and US were included. Four studies (one follow-up and three cross-sectional) found associations between fish consumption and MetS (three among men, and one among women), suggesting that fish consumption may prevent or improve metabolic health and have a protective role in MetS prevention. This protective role might be related to gender, and men may benefit more from the consumption of fish. However, lack of controlling for potential confounders may also inflict the results. Additional research is required to further explore fish consumption and its potential role in improving or reversing MetS and its components.
PMCID: PMC4210541  PMID: 25352919
Metabolic syndrome; Insulin resistance; Diet; Fish intake; Seafood; Consumption of fish; Systematic review
19.  Bezafibrate improves insulin resistance evaluated using the glucose clamp technique in patients with type 2 diabetes mellitus: a small-scale clinical study 
Bezafibrate is mainly used to treat hypertriglyceridemia. Studies have reported that bezafibrate also improves type 2 diabetes mellitus, but the mechanism has not been fully elucidated. We performed euglycemic hyperinsulinemic clamps (glucose clamp) and meal tolerance tests (MTT) to examine the effects of bezafibrate on insulin resistance in patients with type 2 diabetes mellitus.
Twelve Japanese patients with type 2 diabetes mellitus and dyslipidemia (mean age: 59.5 years; fasting plasma glucose: 7.95 mmol/L; hemoglobin A1c [HbA1c]: 7.3%; body mass index: 26.5 kg/m2) underwent a glucose clamp and MTT before and after 12 weeks of treatment with 400 mg/day bezafibrate. The glucose infusion rate was measured during the glucose clamp. The patients took a test meal (460 kcal) in the MTT. Plasma glucose and immunoreactive insulin levels were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum C-peptide immunoreactivity, serum lipids, and liver function markers were also measured during the MTT.
Bezafibrate significantly increased the mean glucose infusion rate from 5.78 ± 1.94 to 6.78 ± 2.52 mg/kg/min (p < 0.05). HbA1c improved from 7.30 ± 0.55% to 7.02 ± 0.52% (p < 0.05). In the MTT, fasting plasma glucose decreased from 7.95 ± 1.15 to 6.98 ± 1.07 mmol/L (p < 0.05). The area under the plasma glucose curve from 0 to 180 min decreased significantly from 29.48 ± 5.07 to 27.12 ± 3.98 mmol/h/L (p < 0.05), whereas immunoreactive insulin was unchanged. Furthermore, bezafibrate also significantly improved serum lipids, with decreases in triglyceride levels from 1.84 ± 0.88 to 1.14 ± 0.41 mmol/L (p < 0.05), low-density lipoprotein cholesterol levels from 3.56 ± 0.83 to 2.92 ± 0.55 mmol/L (p < 0.05), and remnant-like particle cholesterol levels decreased from 0.25 ± 0.16 to 0.14 ± 0.06 mmol/L (p < 0.05), and increases in high-density lipoprotein cholesterol levels from 1.50 ± 0.24 to 1.66 ± 0.29 mmol/L (p < 0.05).
Bezafibrate improved glucose intolerance and peripheral insulin resistance in these Japanese patients with type 2 diabetes mellitus and dyslipidemia. Therefore, bezafibrate could be used to treat insulin resistance in patients with type 2 diabetes mellitus and dyslipidemia.
Trial registration
University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000012462.
PMCID: PMC4213459  PMID: 25360162
Bezafibrate; Type 2 diabetes mellitus; Glucose clamp; Meal tolerance test; Japanese patients; Insulin resistance
20.  Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes 
Glucagon-like peptide-1 (GLP-1) receptor agonists can maintain good glycemic control in some diabetic. Here we compared the clinical characteristics and parameters reflecting glucose metabolism at the time of the initiation of GLP-1 receptor agonist therapy between patients who responded well to therapy and those who did not.
The records of 43 patients with type 2 diabetes who started receiving GLP-1 receptor agonist therapy during hospitalization were retrospectively reviewed. Glucagon stimulation tests were performed, and patients were started on liraglutide or exenatide therapy. Preprandial blood glucose levels were measured on days 2 and 3 of GLP-1 receptor agonist therapy. We used the Cox proportional hazard model to compare clinical parameters between responders (HbA1c level <8% at more than 3 months after the initiation of treatment) and non-responders (HbA1c level ≥8% at more than 3 months after the initiation of treatment or a switch to insulin therapy at any time).
Twenty-six of the 43 patients were classified as non-responders. At baseline, mean HbA1c levels were 9.9% among responders and 9.7% among non-responders. Compared with treatment with only diet or metformin, the hazard ratio [HR] for non-response was 5.3 (95% confidence interval [CI]: 1.16-24.6, P = 0.03) for insulin therapy and 5.0 (95% CI: 1.13-22.16, P = 0.03) for sulfonylurea therapy. Compared with the lowest tertile, the HRs for non-response in the highest tertile were 3.1 (95% CI: 1.04-8.97, P = 0.04) for the mean preprandial blood glucose level on days 2 and 3 and 3.4 (95% CI: 1.05-11.01, P = 0.04) for the body mass index. The response was not significantly associated with the duration of diabetes or the glucagon stimulation test results. A receiver operating curve analysis showed that the mean preprandial blood glucose level had the highest area under the curve value (=0.72) for the prediction of non-responders.
In patients with poorly controlled diabetes, the response to GLP-1 receptor agonist therapy was significantly associated with the treatment used before the initiation of therapy, the body mass index, and the mean preprandial blood glucose level during the 2 days after the initiation of therapy.
PMCID: PMC4209043  PMID: 25349635
Glycemic control; Glucagon-like peptide-1 agonist; Predictors of response; Preprandial blood glucose level; Liraglutide; Exenatide
21.  Assessment of college students’ awareness and knowledge about conditions relevant to metabolic syndrome 
Despite the increasing prevalence of metabolic syndrome among young adults, little is known about the awareness level of college students about this condition. The purpose of this study was to assess students’ level of awareness and knowledge about conditions relevant to metabolic syndrome (MetS).
A self-reported online questionnaire was administered to 243 students attending Central Michigan University. Questions were divided into seven conditions: diabetes, adiposity, hypertension, high serum cholesterol, arteriosclerosis, stroke, and myocardial infarction. Students’ responses were scored and interpreted as follows: poor knowledge if ≤50% of students answered the question correctly; fair knowledge if between 51-80% of students answered the question correctly; and good knowledge if between 81-100% of students answered the question correctly. Anthropometric measurements including height, weight, waist circumference, percentage body fat, and visceral fat score were measured. Fisher’s exact test was used to test the differences in students’ responses. A p value <0.05 was considered a statistically significant difference.
More than 80% of students correctly identified symptoms and complications of diabetes, hypertension, arteriosclerosis, myocardial infarction and stroke, and 92% identified adiposity as a risk factor for heart disease. There were few false beliefs held by students on questionnaire items. For example, 58% of male students falsely believed that individuals with diabetes may only eat special kinds of sweets compared to 39% of females (p < 0.01) and more than half of the students falsely identified liposuction as the best possible treatment in adiposity therapy. Gender, Health Science major, and year in school were found to be positively associated with more knowledge.
The findings in this study suggest that students’ knowledge about conditions relevant to metabolic syndrome can be improved. In this essence, raising awareness about MetS based on students’ pre-existing knowledge is essential to enhance students’ wellness.
PMCID: PMC4213528  PMID: 25360161
Metabolic syndrome; Cardiovascular risk factors; Adiposity; College students; Lay knowledge
22.  Age modification of diabetes-related hospitalization among First Nations adults in Alberta, Canada 
We sought to determine the modifying effects of age and multimorbidity on the association between First Nations status and hospitalizations for diabetes-specific ambulatory care sensitive conditions (ACSC).
We identified 183,654 adults with diabetes from Alberta Canada, and followed them for one year for the outcome of hospitalization or emergency department (ED) visit for a diabetes-specific ACSC. We used logistic regression to determine the association between First Nations status and the outcome, assessing for effect modification by age and multimorbidity with interaction terms. In a model adjusting for age, age2, baseline A1c, duration of diabetes, and multimorbidity, First Nations people were at greater risk than non-First Nations to experience a diabetes-specific hospitalization or ED visit (unadjusted odds ratio [OR] 3.74; 95% confidence interval [CI]: 3.45-4.07). After adjustment for relevant covariates, this association varied by age (interaction: p = 0.018): adjusted OR 3.94 (95% CI: 3.11-4.99) and 5.74 (95% CI: 3.36-9.80) for First Nations compared to non-First Nations at ages 30 and 80 years, respectively.
Compared with non-First Nations, older First Nations patients with diabetes are at greater risk for diabetes-specific hospitalizations. Older First Nations patients with diabetes should be given priority access to primary care services as they are at greatest risk for requiring hospitalization for stabilization of their condition.
PMCID: PMC4192759  PMID: 25309626
American indian; First Nations; Hospitalization; Diabetes mellitus; Risk adjustment
23.  Association and interaction analysis of PPARGC1A and serum uric acid on type 2 diabetes mellitus in Chinese Han population 
Peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1A/ PGC-1α) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. The activity of PGC-1α or genetic variations in the gene encoding the enzyme may contribute to individual variations in mitochondrial function and insulin resistance or diabetes. The objective of this study was to assess the extent to which PPARGC1A (rs8192678) and serum uric acid (UA) and its interaction impact on T2DM susceptibility in Chinese Han population.
We conducted a study in a cohort that included 1166 T2DM patients and 1135 controls, and was genotyped for the presence of the PPARGC1A rs8192678 polymorphisms. Genotyping was performed by iPLEX technology. The association between rs8192678 or UA and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis controlling for confounders. The interaction between rs8192678 and UA for T2DM susceptibility was also assessed by MLR analysis.
The generalized linear regression analysis failed to show an association between the PPARGC1A rs8192678 polymorphisms and T2DM. Interestingly, the present study provided data suggesting that the minor A-allele of PPARGC1A (rs8192678) had a protective effect against T2DM in subjects with higher level of UA (ORint =1.50 95% CI: 1.06-2.12 for allele and P = 0.02, ORint =1.63 95% CI: 1.17-2.26 for genotype and P = 0.004).
The combination of higher level of UA and PPARGC1A (rs8192678) was an independent predictor for T2DM.
PMCID: PMC4190481  PMID: 25302081
PPARGC1A; Serum uric acid; Interaction; Type 2 diabetes mellitus; Chinese Han population
24.  Low serum galectin-3 concentrations are associated with insulin resistance in patients with type 2 diabetes mellitus 
Galectin-3 is a family of soluble beta-galactoside-binding lectins that play many important regulatory roles in inflammation. Galectin-3-deficient mice have been shown to exhibit excess adiposity, hyperglycemia, insulin resistance and systemic inflammation. We investigated the association between serum galectin-3 and insulin resistance in patients with type 2 diabetes using a glucose clamp method.
This was a cross-sectional study. Twenty patients (mean fasting plasma glucose 7.6 mmol/L, HbA1c 7.2%, BMI 28.1 kg/m2) underwent a meal tolerance test and glucose clamp test. Participants were given a test meal and plasma glucose and insulin were measured at 0, 30, 60, 120 and 180 min. The glucose disposal rate was measured during hyperinsulinemic-euglycemic glucose clamps. Serum galectin-3 levels were measured using the enzyme-linked immunosorbent assay method.
The mean serum galectin-3 level was 5103 pg/ml. Galectin-3 levels correlated significantly with the glucose disposal rate (R = 0.71, P < 0.001), fasting insulin (R = −0.56, P < 0.01), homeostasis model assessment for insulin resistance (R = −0.52, P < 0.05), and the insulin sensitivity index (R = 0.62, P < 0.005). Galectin-3 levels also positively correlated with the serum adiponectin level (R = 0.61, P < 0.05), but not with the high-sensitive C-reactive protein and interleukin-6 and −10.
These results suggest that low levels of serum galectin-3 are associated with insulin resistance in patients with type 2 diabetes.
PMCID: PMC4190474  PMID: 25302080
Galectin-3; Insulin resistance; Type 2 diabetes mellitus
25.  Metabolic syndrome-breast cancer link varies by intrinsic molecular subtype 
Metabolic syndrome (MS) has been shown to increase the risk of breast cancer. Existing data suggest that the strength of metabolic syndrome-breast cancer link varies by intrinsic molecular subtype, but results from worldwide literature are controversial. Primary endpoint of the study was to assess whether MS is a predictor of specific breast cancer (BC) subtype. Secondary endpoint was to determine whether components of MS can individually increase the risk of specific breast cancer subtype.
Anthropometric and metabolic variables were correlated to breast cancer specific subgroups, retrospectively. Statistical significance was considered when p ≤ 0.05 and 95% CI.
Data analysis suggests that MS per se represents a modifiable risk factor for BC in postmenopausal [OR 6.28 (95% CI 2.79-14.11) p < 0.00001]. MS per se prevalence is higher among Luminal breast cancers in postmenopausal [OR 1.37 (95% CI 1.07-2.80) p = 0.03]. Body Mass Index (BMI) alone is associated to Luminal A subtype breast cancer risk [OR 1.12 (95% CI 0.96-2.196 p = 0.2]. Waist Circumference > 88 cm has been shown to be specifically and statistically significant associated to HER-2+ breast cancer subtypes in postmenopausal [OR 2.72 (95% CI 1.69- 10.72) p = 0.01], whilst in Luminal B it was only marginally statistical associated [OR 2.21 (95% CI 0.77-2.60) p = 0.1]. Insulin resistance showed statistical significant association to HER-2+ and Luminal B tumors [OR 2.11 (95% CI 1.66-6.69) p = 0.05] and [OR 2.33 (95% CI 1.2-4.2) p = 0.006], respectively. Hence, it has emerged that BMI is weakly associated to Luminal A breast cancers in this case series, whereas visceral obesity and insulin resistance are likely to be linked to more aggressive breast cancer subtypes.
New molecular biomarkers unveiling metabolic syndrome related breast carcinogenesis need to be detected to further stratify breast cancer risk by subtypes.
PMCID: PMC4183766  PMID: 25285159
Metabolic syndrome; Breast cancer; Molecular subtype; Insulin-resistance; BMI; Waist circumference

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