Metabolic syndrome in metabolic obese, non-obese elderly in northern Taiwan

Background: The prevalence of metabolic syndrome is high in non-obese adult individuals, but less research focusing on elderly group. We aimed to assess the prevalence rates of metabolic syndrome (MetS) and its individual components in metabolic obese, non-obese elderly population in northern Taiwan (body mass index [BMI] 2). Methods: A cross-sectional survey was conducted among elderly people (≥65 y/o) who received a senior citizen health examination from March to November 2009. A total of 1180 participants (433 men, 36.7%;748 women, 63.3%) were investigated. The prevalence and odds ratios of metabolic syndrome, as defined by the modified Adult Treatment Panel III (ATP III), were analyzed in the following BMI groups: 2, 18.5 - 24 kg/m2, 24 - 27 kg/m2, and ≥27 kg/m2. Results: The prevalence of metabolic syndrome increased with BMI in both women and men (P 2, and 1.09 (1.02 - 1.17) for men with BMI 24 - 27 kg/m2. Conclusions: Elderly individuals in the BMI belong to normal and overweight groups have a relatively high prevalence and increased risk of developing MetS. Therefore, physicians should perform screening examinations for MetS and its risk factors not only in obese patients but also in non-obese elderly patients to prevent Mets. This electronic document is a “live” template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.

Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline

Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.

Evaluation of Lipid Profile in Obese and Non-Obese Hypertensive Adult Patients Attended in Medicine Department of a Medical College Hospital of Bangladesh

Background: By the dawn of this modern era of science, the prime challenge of physician is cardiovascular disease (CVD). The most important modifiable risk factors of CVDs are unhealthy diet, physical inactivity and tobacco use. The effects of unhealthy diet and physical inactivity include abnormal blood lipid, obesity and hypertension. We tried to evaluate and correlate the pattern of lipid profile in obese and non-obese hypertensive patients. Objectives: This study was conducted at medicine department of Cumilla Medical College Hospital. The principal aim was to evaluate the lipid profile in obese and non-obese adult hypertensive patients. Methodology: During this cross sectional analytical study, a total of 100 adult hypertensive patients were taken by purposive sampling. Among them 50 (group 1) patients were taken those were obese and 50 (group 2) patients taken those were non-obese according to BMI measurement on operational definition. Diagnosis of hypertension would be established with the help of ambulatory BP measurements two occasions few minutes apart. The staging of hypertension was done according to JNC7 Criteria. Morning blood samples were taken after 8 - 12 hours of fasting and lipid profiles were done on authentic laboratories. The laboratory values were interpreted according to the operational definition of dyslipidaemia. The ethical research and review committee approved the study protocol and signed informed consent was obtained from the participants. The statistics was analyzed using the IBM SPSS software of version 19.0. Statistical significance was set at p < 0.05. Results: Among the two groups, there were 56 (56%) males and 44 (44%) females. The mean age of group 1 (46.10 ± 11.09) was compared to that of group 2 (45.5 ± 10.6). Lipid profile abnormalities were significantly higher in the stage 2 hypertension (59.62%) and stage 3 hypertension (66.66%), higher in class 2 obese (100%) and class 3 obese subjects (100%), female hypertensive patients had significantly higher BMI than their male counterparts (27.24 ± 3.63 kg/m2 versus 29.29 ± 3.99 kg/m2), lipid profiles were higher in the female than male hypertensive patients (63.33% vs 55.35%) but only TC was statistically significant (4.45 ± 1.19 mmol/l versus 4.86 ± 1.29 mmol/l, p < 0.05). Those who were obese had significant high TG (p < 0.001), high TC (p < 0.001) and high LDL-C (p < 0.001). 38 (76%) of the obese hypertensive patients had dyslipidaemia whereas 21 (42%) of non-obese hypertensive patients had dyslipidaemia. In multivariate regression, TG was significantly and directly associated with BMI of subjects. Dyslipidaemia was more prevalent in the age group 30 - 59 of adult hypertensive patients. It showed that obese hypertensive patients had significantly higher SBP (p < 0.001), DBP (p < 0.001) than non-obese subjects. The mean TC (4.83 ± 0.95 mmol/l versus 4.15 ± 0.57 mmol/l, t = -9.70, p < 0.001), TG (2.64 ± 0.67 mmol/l versus 2.10 ± 0.45 mmol/l, t = -5.37, p < 0.001) and LDL-C (3.00 ± 0.82 mmol/l versus 2.44 ± 0.53 mmol/l, t = -9.11, p < 0.001) were also significantly higher among the hypertensive obese subjects. The mean HDL-C was however comparable in the two groups (1.25 ± 0.27 mmol/l versus 1.24 ± 0.57 mmol/l, t = -0.25, p = 0.08)...

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Mesenchymal stromal cells modulate unfolded protein response and preserve β-cell mass in type 1 diabetes

Introduction:Transplantation of mesenchymal stromal cells(MSCs)is a promising therapy for type 1 diabetes(T1D).However,whether the infused MSCs affect the endoplasmic reticulum stress or subsequent unfolded protein response inβcells remains unclear.Methods:To investigate this,we induced early-onset T1D in non-obese diabetic mice using streptozotocin.Subsequently,T1D mice were randomly assigned to receive either MSCs or phosphate-buffered saline.We observed the in vivo homing of MSCs and assessed their effectiveness by analyzing blood glucose levels,body weight,histopathology,pancreatic protein expression,and serum levels of cytokines,proinsulin,and C-peptide.Results:Infused MSCs were found in the lungs,liver,spleen,and pancreas of T1D mice.They exhibited various effects,including reducing blood glucose levels,regulating immunity,inhibiting inflammation,increasingβ-cell areas,and reducing the expression of key proteins in the unfolded protein response pathway.Fasting serum proinsulin and C-peptide levels were significantly higher in the MSCs treatment group than in the T1D model group.However,there was no significant difference in the biomarker ofβ-cell endoplasmic reticulum stress,the ratio of fasting serum proinsulin to C-peptide,between the two groups.Conclusion:Ourfindings reveal that MSCs infusion does not alleviate endoplasmic reticulum stress inβcells directly but modulates the unfolded protein response pathway to preserveβ-cell mass and function in T1D mice.

Impact of nonalcoholic fatty liver disease on the risk of gallbladder polyps in lean and non-obese individuals:A cohort study

Background:The association between non-obese or lean nonalcoholic fatty liver disease(NAFLD)and gallbladder polyps(GBPs)has not yet been evaluated.We aimed to determine whether NAFLD is an independent risk factor for the development of GBPs,even in non-obese and lean individuals.Methods:We analyzed a cohort of 331208 asymptomatic adults who underwent abdominal ultrasonography(US).The risk of GBP development was evaluated according to the obesity and NAFLD status.Results:The overall prevalence of NAFLD and GBPs≥5 mm was 28.5%and 2.9%,respectively.The prevalence of NAFLD among 160276 lean,77676 overweight and 93256 obese participants was 8.2%,31.2%,and 61.1%,respectively.Individuals with NAFLD had a significantly higher incidence of GBPs with a size of≥5 mm[adjusted odds ratio(OR)=1.18;95%confidence interval(CI):1.11–1.25].A higher body mass index and its categories were also significantly associated with an increased risk of GBPs≥5 mm.Moreover,risk of GBPs≥5 mm was significantly increased even in NAFLD individuals who are not obese(lean:adjusted OR=1.36,95%CI:1.19-1.54;overweight:adjusted OR=1.14,95%CI:1.03–1.26,respectively).Conclusions:Non-obese/lean NAFLD is an independent risk factor for GBP development,suggesting that NAFLD may play an important role in the pathogenesis of GBPs regardless of the obesity status.Therefore,a more thorough evaluation for GBPs may be necessary when hepatic steatosis is detected on abdominal US,even in non-obese or lean individuals.

Triptolide prolonged allogeneic islet graft survival in chemically induced and spontaneously diabetic mice without impairment of islet function

BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo. METHODS: We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic non-obese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group. RESULTS: The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks. CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function. (Hepatobiliary Pancreat Dis Int 2010; 9: 312-318)

Diabetic neuropathy research: from mouse models to targets for treatment

Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.

Genetic susceptibility to autoimmune liver disease

Autoimmune hepatitis(AIH),primary sclerosing cholangitis(PSC) and primary biliary cirrhosis(PBC) are considered as putative autoimmune diseases of the liver.Whereas strong evidence that bacterial infection may trigger PBC exists,the etiologies for PSC and AIH remain unknown.Although there have been significant discoveries of genetic polymorphisms that may underlie the susceptibility to these liver diseases,their associations with environmental triggers and the subsequent implications have been difficult to elucidate.While single nucleotide polymorphisms within the negative costimulatory molecule cytotoxic T lymphocyte antigen 4(CTLA-4) have been suggested as genetic susceptibility factors for all three disorders,we discuss the implications of CTLA-4 susceptibility alleles mainly in the context of PBC,where Novosphingobium aromaticivorans,an ubiquitous alphaproteobacterium,has recently been specifically associated with the pathogenesis of this devastating liver disease.Ultimately,the discovery of infectious triggers of PBC may expand the concept of genetic susceptibility in immune-mediated liver diseases from the concept of aberrant immune responses against self-antigens to insufficient and/or inappropriate immunological defense mechanisms allowing microbes to cross natural barriers,establish infection and damage respective target organs.

Nonalcoholic fatty liver disease in lean subjects:Prognosis,outcomes and management

Nonalcoholic fatty liver disease(NAFLD)accounts for most cases of chronic liver disease worldwide,with an estimated global prevalence of approximately 25%and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis.NAFLD is strongly connected to metabolic syndrome,and for many years,fatty liver was considered to be an exclusive feature of obese patients.However,recent studies have highlighted the presence of NAFLD in non-obese subjects,with or without increased visceral fat or even in lean subjects without increased waist circumference.“Lean NAFLD”is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology,prognosis and management compared with NAFLD in overweight/obese patients.In the present editorial,we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries.Moreover,we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population.Finally,we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and nonlean cohorts.

The pattern of plasma BCAA concentration and liver Bckdha gene expression in GK rats during T2D progression

Background: This study was conducted to measure the concentration of branched chain amino acid(BCAA) in different species and detect the expression pattern of the liver Bckdha gene in Goto-Kakizaki(GK) rats during type 2 diabetes(T2D)progression.Methods: We measured the concentration of BCAA in GK rats, induced T2D cynomolgus monkeys and T2D humans by liquid chromatography tandem mass spectrometry, and used real-time quantitative PCR to analyze the gene expression of Bckdha and Bckdk, which encode the rate-limiting enzymes in catabolism of,respectively, branched chain amino acids and branched chain α-keto acid dehydrogenase kinase.Results: In this study, we showed that GK rat BCAA concentrations were significantly reduced at 4 and 8 weeks(P < 0.05 and P < 0.01, respectively), while the expression of Bckdha in GK rat liver was increased at 4 and 8 weeks(1.62-fold and1.93-fold, respectively). The BCAA concentrations were significantly reduced in diet-induced T2D cynomolgus monkeys(P < 0.01), but significantly increased in T2D humans(P < 0.001).Conclusions: Our results showed that BCAA concentrations changed at different times and by different amounts in different species and during different periods of T2D progress, and the significant changes of BCAA concentration in the three species indicated that BCAA might participate in the progress of T2D. The results suggested that the increased expression of Bckdha in GK rat liver might partially explain the reduced plasma BCAA concentration at 4 and 8 weeks. Further studies are required to investigate the exact mechanism of BCAA changes in non-obese T2D.

Diabetes-related impairment in bone strength is established early in the life course

AIM: To evaluate properties of bone quantity/quality using young non-obese Type 1(T1D)-diabetic(NOD) prone and syngenic non-diabetic(NOD.scid) mice.METHODS: Quantitative bone assessment of tibia was conducted using dual-energy X-ray absorptiometry(DXA) for the evaluation of body mass,bone mineral content,body fat mass and lean mass.Qualitative assessment was accomplished by three-point breakage for assessment of force to failure and micro-computed tomography for evaluation of trabecular and cortical properties of bone.In addition,fasting blood was evaluated prior to sacrifice at week eleven and fifteen to evaluate and compare glucose homeostasis between the strains of mice.RESULTS: Our findings support a perturbation in the relationship between bone quantity,quality,and subsequently,the association between structure and strength.There were no differences in DXA-assessed body composition(body fat,% fat mass and lean mass) and bone composition(bone mineral content and bone mineral density) between strains.However,relative to NOD.scid,NOD mice had lower trabecular bone volume,relative trabecular bone volume,trabecular number and trabecular total material density(P < 0.05).Conversely,NOD mice had greater cortical total mean volume(P < 0.05).General linear models analysis adjusted for body weight revealed a significant contribution of T1D to bone health as early as 5 wk.CONCLUSION: It is well-established that diabetes is a significant risk factor for increased fractures,although the underlying mechanisms are not fully understood.Investigation of bone parameters encompassing strength and structure early in the life course will facilitate the elucidation of the pathogenesis of impaired bone integrity.

Mitochondrial haplogroups associated with Japanese centenarians, Alzheimer's patients, Parkinson's patients, type 2 diabetic patients and healthy non-obese young males

The relationships between five classes of Japanese people （i.e., 96 centenarians, 96 Alzheimer＇s disease （AD） patients, 96 Parkinson＇s disease （PD） patients, 96 type 2 diabetic （T2D） patients, and 96 healthy non-obese young males） and their mitochondrial single nucleotide polymorphism （mtSNP） frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function （RBF） network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups： Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4cl, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8al, G, D4, and F1; and Japanese healthy non-obese young males-D4g and D4b1b. From the points of common haplogroups among the five classes, the cente- narians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians （over 105 years old） recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person＇s mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.

Non-alcoholic Fatty Liver Disease in Lean Subjects:Characteristics and Implications

Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects;however,it is not rare among lean individuals.Given the absence of traditional risk factors,it tends to remain under-recognised.The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients.Though results from several studies have been mixed,it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD.Several genetic variants are associated with NAFLD without insulin resistance.Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD;however,the former tend to have less severe disease at presentation.The underlying pathophysiology of lean NAFLD may be quite different.Genetic predispositions,fructose-and cholesterol-rich diet,visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings.Lean NAFLD may pose a risk for metabolic disturbances,cardiovascular morbidity or overall mortality.Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD.The effectiveness of various treatment modalities,such as exercise and pharmacotherapy,on lean NAFLD is not known.Weight loss is expected to help lean NAFLD patients who have visceral obesity.Further investigation is needed for many aspects of lean NAFLD,including mechanistic pathogenesis,risk assessment,natural history and therapeutic approach.