ABSTRACT
OBJECTIVES: Sinonasal inverted papilloma has a high tendency for recurrence, local bone destruction and risk of malignant transformation. Therefore, complete resection of the tumour is required, and close follow up is essential. This article describes the clinical outcomes, recurrence rate and malignant transformation rate of sinonasal inverted papilloma. METHODS: In this study, 139 patients diagnosed with sinonasal inverted papilloma in our hospital from December 2010 to May 2022 were retrospectively analysed. All patients underwent endoscopic surgery. RESULTS: Sinonasal inverted papilloma occurred more often in males than in females. The mean age of patients with sinonasal inverted papilloma was 67.3 ± 5.7 years at diagnosis. The most prevalent site of origin was the maxillary sinus (50.4 per cent). The recurrence rate was 5.75 per cent, and the malignant transformation rate was 6.5 per cent. CONCLUSION: All patients in this study underwent endoscopic surgery. Meticulous resection and regular long-term follow ups are crucial to reducing sinonasal inverted papilloma recurrence after surgery.
Subject(s)
Papilloma, Inverted , Paranasal Sinus Neoplasms , Male , Female , Humans , Middle Aged , Aged , Retrospective Studies , Paranasal Sinus Neoplasms/epidemiology , Paranasal Sinus Neoplasms/surgery , Papilloma, Inverted/surgery , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , EndoscopyABSTRACT
OBJECTIVE: To analyse the treatment results of bilobed flap reconstruction performed for skin defects after parotid carcinoma surgery. METHOD: Ten patients who underwent bilobed flap reconstruction for skin defects after parotid carcinoma surgery in our hospital, from 2014 to 2020, were retrospectively enrolled. RESULTS: All patients underwent bilobed flap reconstruction for skin defects after parotid carcinoma surgery. The size of the skin defect was 2.7 × 2.2 cm in the smallest dimension and 9.0 × 6.3 cm in the largest dimension. All bilobed flaps except one healed without any problems. One patient developed partial flap necrosis in the retroauricular region, and was treated with skin grafts after removal of the necrotic tissue under local anaesthesia. All bilobed flaps, including the cases in which skin grafts were performed, survived after post-operative radiotherapy or chemotherapy. CONCLUSION: A bilobed flap is a good reconstruction option for skin defects after parotid carcinoma surgery in some cases.
Subject(s)
Carcinoma/surgery , Dermatologic Surgical Procedures , Parotid Neoplasms/surgery , Surgical Flaps , Aged , Aged, 80 and over , Carcinoma/pathology , Face/surgery , Female , Humans , Male , Middle Aged , Neck/surgery , Parotid Neoplasms/pathology , Republic of Korea , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: This study aimed to analyse the results of chyle fistula testing using the SD LipidoCare system in patients who had undergone neck dissections performed in our hospital in 2019. METHOD: Sixty patients who underwent neck dissections from March 2019 to November 2019 were identified based on their medical records. RESULTS: Post-operative chyle fistulas were observed in 3 of 60 patients (5 per cent). All patients who developed chyle fistulas had undergone left-sided neck dissections. Within 3 minutes, the SD LipidoCare test had produced triglyceride results of 49, 56 and 207 mg/dl in the three patients. The remaining 57 patients measured 'low' for triglycerides on the SD LipidoCare test system. CONCLUSION: The SD LipidoCare test quickly and accurately diagnosed chyle fistulas in patients who had undergone neck dissections. All patients improved with conservative treatment following the early diagnosis of chyle fistulas.
Subject(s)
Fistula/diagnosis , Hematologic Tests/instrumentation , Neck Dissection/adverse effects , Postoperative Complications/diagnosis , Triglycerides/analysis , Adult , Chyle , Early Diagnosis , Female , Hematologic Tests/methods , Humans , Male , Middle Aged , Neck Dissection/methods , Reproducibility of ResultsABSTRACT
AIM: To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: 1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy. RESULTS: 388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 [95% CI 1.14-2.36], and 2.92 [95% CI 1.76-4.87] in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 [95% CI 0.49-1.06], and 0.51 [95% CI 0.29-0.90]) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10). CONCLUSION: Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Age of Onset , Cross-Sectional Studies , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Humans , Prospective Studies , Risk FactorsABSTRACT
AIM: To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. METHODS: Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. RESULTS: Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. CONCLUSIONS: Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Renal Insufficiency, Chronic/blood , Seminal Plasma Proteins/blood , Aged , Albuminuria , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Disease Progression , Female , Glomerular Filtration Barrier , Humans , Male , Middle Aged , Proportional Hazards Models , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/urine , Retrospective Studies , Zn-Alpha-2-GlycoproteinABSTRACT
OBJECTIVES: To analyse the results of treatment for nasolabial cysts according to whether an intraoral sublabial or endoscopic transnasal approach was used, and to determine the recent surgical trend in our hospital. METHODS: Twenty-four patients with a histopathologically and radiologically confirmed nasolabial cyst between January 2010 and December 2017 were enrolled in this study. RESULTS: Nasolabial cysts were predominant in females (91.7 per cent) and on the left side (54.2 per cent). Treatment involved an intraoral sublabial approach in 12 cases (48.0 per cent) and a transnasal endoscopic approach in 13 cases (52.0 per cent). In 13 cases (52.0 per cent) surgery was performed under local anaesthesia, while in 12 cases (48.0 per cent) it was conducted under general anaesthesia. The most common post-operative complications were numbness of the upper lip or teeth (n = 9, 36.0 per cent). Only one patient (4.0 per cent), who underwent a transnasal endoscopic approach, experienced a reoccurrence. CONCLUSION: Surgical resection through an intraoral sublabial or transnasal endoscopic approach is the best treatment for a nasolabial cyst, showing very good results and a low recurrence rate. The recent surgical trend in our hospital is to treat nasolabial cysts using a transnasal endoscopic approach under local anaesthesia.
ABSTRACT
Mammary analogue secretory carcinoma (MASC) of the salivary gland is a newly-described, rare, malignant tumour. Few patients present with MASC of the parotid gland, so the exact characteristics, outcomes of treatment, and prognosis are unknown. The aim of this study was to analyse the clinical features and outcomes of treatment of MASC of the parotid gland in patients being treated at a single hospital. Five patients with histopathologically-confirmed MASC of the parotid gland between January 2015 and August 2018 were retrospectively enrolled. In all cases preoperative fine-needle aspiration cytology had failed to provide an accurate diagnosis. All patients underwent a macroscopically complete oncological resection. Two patients had postoperative radiotherapy (RT). On immunohistochemical examination all tumours stained for S-100 and mammaglobin but not for DOG1. There were no regional recurrences or distant metastases in any of the patients at their last follow-up. We obtained good results for patients with MASC of the parotid gland with surgical treatment and postoperative RT.
Subject(s)
Mammary Analogue Secretory Carcinoma , Salivary Gland Neoplasms , Biomarkers, Tumor , Humans , Neoplasm Recurrence, Local , Parotid Gland , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: For over four decades, Clostridium difficile has been a significant enteric pathogen of humans. It is associated with the use of antimicrobials that generally disrupt the microbiota of the gastrointestinal tract. Previously, it was thought that C. difficile was primarily a hospital-acquired infection; however, with the emergence of community-associated cases, and whole-genome sequencing suggesting the majority of the hospital C. difficile infection (CDI) cases are genetically distinct from one another, there is compelling evidence that sources/reservoirs of C. difficile outside hospitals play a significant role in the transmission of CDI. OBJECTIVES: To review the 'One Health' aspects of CDI, focusing on how community sources/reservoirs might be acting as a conduit in the transfer of C. difficile between animals and humans. The importance of a One Health approach in managing CDI is discussed. SOURCES: A literature search was performed on PubMed and Web of Science for relevant papers published from 1 January 2000 to 10 July 2019. CONTENT: We present evidence that demonstrates transmission of C. difficile in hospitals from asymptomatic carriers to symptomatic CDI patients. The source of colonization is most probably community reservoirs, such as foods and the environment, where toxigenic C. difficile strains have frequently been isolated. With high-resolution genomic sequencing, the transmission of C. difficile between animals and humans can be demonstrated, despite a clear epidemiological link often being absent. The ways in which C. difficile from animals and humans can disseminate through foods and the environment are discussed, and an interconnected transmission pathway for C. difficile involving food animals, humans and the environment is presented. IMPLICATIONS: Clostridium difficile is a well-established pathogen of both humans and animals that contaminates foods and the environment. To manage CDI, a One Health approach with the collaboration of clinicians, veterinarians, environmentalists and policy-makers is paramount.
Subject(s)
Carrier State/transmission , Clostridioides difficile/classification , Clostridium Infections/transmission , Cross Infection/transmission , Animals , Clostridioides difficile/genetics , Community-Acquired Infections/transmission , Environmental Microbiology , Food Microbiology , Genome, Bacterial , Humans , One Health , Whole Genome SequencingABSTRACT
Dental migration into the ethmoid sinus is extremely rare. Furthermore, it is very unusual that a displaced dental implant is associated with a concomitant fungus ball in the ethmoid sinus. Herein, we report an unusual case of the coexistence of a dental implant and fungus ball in the ethmoid sinus. It appears that this condition has not been reported previously.
Subject(s)
Dental Implants , Ethmoid Sinus , Endoscopy , Fungi , Maxillary SinusABSTRACT
Synchronous benign and malignant tumours in the ipsilateral parotid gland are rare. We present a case of pleomorphic adenoma and oncocytic carcinoma in the same parotid gland. Clinicians should be aware of the possibility of such synchronous multiple tumours, and that careful dissection and palpation during operation are important to diagnose them.
Subject(s)
Adenoma, Pleomorphic/pathology , Carcinoma/pathology , Neoplasms, Multiple Primary/pathology , Parotid Neoplasms/pathology , Adenoma, Pleomorphic/diagnostic imaging , Adenoma, Pleomorphic/surgery , Carcinoma/diagnostic imaging , Carcinoma/surgery , Humans , Male , Middle Aged , Neoplasms, Multiple Primary/diagnostic imaging , Neoplasms, Multiple Primary/surgery , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/surgery , Tomography, X-Ray ComputedABSTRACT
Retropharyngeal lipoma in a child is an extremely rare pathological entity. The unusual case of a child with a retropharyngeal lipoma presenting with snoring is reported. Retropharyngeal lipoma should be considered in the differential diagnosis of snoring in children.
Subject(s)
Lipoma/diagnosis , Lipoma/surgery , Pharyngeal Neoplasms/diagnosis , Pharyngeal Neoplasms/surgery , Child , Diagnosis, Differential , Endoscopy , Female , Humans , Snoring , Tomography, X-Ray ComputedABSTRACT
AIM: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes. METHODS: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses. RESULTS: Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end-stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end-stage renal disease (Pinteraction = 0.003). A 1-sd increment in fibroblast growth factor 21 (natural log-transformed) was associated with a 1.32-fold (95% CI 1.05-1.66, P = 0.02) increased hazard for end-stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub-distribution hazard ratio 1.35 (95% CI 1.11-1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end-stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89-1.28, P = 0.49)]. CONCLUSIONS: Plasma fibroblast growth factor 21 level independently predicted risk of progression to end-stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study.
Subject(s)
Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/metabolism , Fibroblast Growth Factors/metabolism , Kidney Failure, Chronic/metabolism , Aged , Albuminuria , Asian People , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Disease Progression , Female , Glomerular Filtration Rate , Humans , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/etiology , Male , Middle Aged , Prognosis , Proportional Hazards Models , Prospective Studies , Risk Factors , Sex Factors , Singapore/epidemiologyABSTRACT
AIMS: The incidence of community-associated Clostridium difficile infection (CA-CDI) in Australia has increased since mid-2011. With reports of clinically important C. difficile strains being isolated from retail foods in Europe and North America, a foodborne source of C. difficile in cases of CA-CDI is a possibility. This study represents the first to investigate the prevalence and genotypes of C. difficile in Australian retail vegetables. METHODS AND RESULTS: A total of 300 root vegetables grown in Western Australia (WA) were collected from retail stores and farmers' markets. Three vegetables of the same kind bought from the same store/market were treated as one sample. Selective enrichment culture, toxin profiling and PCR ribotyping were performed. Clostridium difficile was isolated from 30% (30/100) of pooled vegetable samples, 55·6% of organic potatoes, 50% of nonorganic potatoes, 22·2% of organic beetroots, 5·6% of organic onions and 5·3% of organic carrots. Over half (51·2%, 22/43) the isolates were toxigenic. Many of the ribotypes of C. difficile isolated were common among human and Australian animals. CONCLUSIONS: Clostridium difficile could be found commonly on retail root vegetables of WA. This may be potential sources for CA-CDI. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enhances knowledge of possible sources of C. difficile in the Australian community, outside the hospital setting.
Subject(s)
Clostridioides difficile/isolation & purification , Plant Roots/microbiology , Vegetables/microbiology , Animals , Beta vulgaris/microbiology , Clostridioides difficile/classification , Clostridioides difficile/genetics , Clostridioides difficile/growth & development , Daucus carota/microbiology , Humans , Onions/microbiology , Polymerase Chain Reaction , Prevalence , Ribotyping , Solanum tuberosum/microbiology , Western AustraliaABSTRACT
AIM: To gain insight into the presence of islet cell autoimmunity in an ethnic Asian compared with a white European population. METHODS: For this cross-sectional study we recruited people with adult-onset diabetes (age of diagnosis 20-60 years), at tertiary referral centres in Germany (n=1020) and Singapore (n=1088). Glutamic acid decarboxylase and islet antigen 2 antibodies were measured according to Islet Autoantibody Standardization Program protocols. RESULTS: The prevalence of glutamic acid decarboxylase antibody positivity was 13.9% (95% CI 12.1-16.0; P<0.001) in the white European cohort compared with 6.8% (95% CI 5.5-8.4; P<0.001) in the Asian cohort. Glutamic acid decarboxylase antibody positivity was 11.4% (95% CI 7.7-16.6) in Indian, 6.0% (95% CI 3.6-9.9) in Malay and 5.8% (95% CI 4.3-7.7; P<0.001) in Chinese participants. In the white European participants, the prevalence of islet antigen 2 antibody positivity was 7.8% (95% CI 6.4-9.4) compared with 14.8% (95% CI 12.8-17.0; P<0.001) in the Asian cohort as a whole, and among the three ethnicities in the Asian cohort it was 12.4% (95% CI 8.6-17.7) in Indian, 16.8% (95% CI 12.6-22.2) in Malay and 15.7% (95% CI 13.2-18.6) in Chinese participants. Double antibody positivity was seen in 5.7% (95% CI 4.5-7.1) of white European participants compared with 1.6% (95% CI 1.0-2.5; P<0.01) of Asian participants. In the white European cohort, those who were glutamic acid decarboxylase autoantibody-positive had a lower BMI than those who were autoantibody-negative, but this trend was absent in the Asian cohort. CONCLUSIONS: A marked prevalence of islet cell autoimmunity was observed in people with adult-onset diabetes. While glutamic acid decarboxylase antibodies were more frequent in the European cohort, islet antigen 2 antibody positivity was highest in the three ethnic groups in Singapore, suggesting ethnic-specific differences in antibody profiles.
Subject(s)
Autoantibodies/analysis , Autoimmune Diseases/immunology , Autoimmunity , Diabetes Mellitus, Type 2/immunology , Glutamate Decarboxylase/antagonists & inhibitors , Receptor-Like Protein Tyrosine Phosphatases, Class 8/antagonists & inhibitors , Adult , Asian People , Autoimmune Diseases/blood , Autoimmune Diseases/epidemiology , Autoimmune Diseases/ethnology , Biomarkers/blood , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/ethnology , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Referral and Consultation , Singapore/epidemiology , Tertiary Care Centers , White People , Young AdultABSTRACT
INTRODUCTION: Sclerosing mucoepidermoid carcinoma of the salivary gland is a rare subtype of mucoepidermoid carcinoma. The most common site of sclerosing mucoepidermoid carcinoma of the salivary glands is the parotid gland, followed by the submandibular gland, and the minor salivary glands. OBSERVATION: Here we report the first case of sclerosing mucoepidermoid carcinoma of the sublingual gland. DISCUSSION: Clinicians should consider sclerosing mucoepidermoid carcinoma in the differential diagnosis of salivary gland neoplasm. Surgical excision with clear margins seems to be a sufficient initial treatment option for sclerosing mucoepidermoid carcinoma of the salivary gland.
Subject(s)
Carcinoma, Mucoepidermoid/diagnosis , Salivary Gland Neoplasms/diagnosis , Sublingual Gland/pathology , Aged , Biopsy, Fine-Needle/methods , Carcinoma, Mucoepidermoid/surgery , Diagnosis, Differential , Female , Humans , Salivary Gland Neoplasms/surgery , Sublingual Gland/surgery , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
BACKGROUND: Leptomeningeal dissemination of hemangioblastomas (HB) of the central nervous system (CNS) is extremely rare. Few studies have reported leptomeningeal involvement in sporadic HB or in HB associated with von Hippel-Lindau syndrome. The clinical and radiological features of leptomeningeal involvement in HB after surgery have not been described in detail. MATERIALS AND METHODS: This retrospective case review involved patients from three different tertiary referral centers with leptomeningeal dissemination of HB after surgery for the primary mass. A literature review was also performed to describe the clinical and radiological characteristics and long-term outcomes of patients who developed leptomeningeal dissemination after initial surgical resection. RESULTS: This study included seven patients, five males and two females, ranging in age from 36 to 54 years. Incidence of leptomeningeal dissemination in patients with HB was about 4.3 % (3/69). It appeared at a mean 94.9 months (range, 39-204 months) after gross total resection of CNS HBs. Three of the seven patients died 5, 38, and 79 months, respectively, after diagnosis of leptomeningeal dissemination. Review of the literature identified 21 patients with characteristics of leptomeningeal dissemination similar to those in our series. CONCLUSIONS: Leptomeningeal dissemination of HB is a rare pattern of long-term recurrence. Long-term outcomes may be fatal. The long developmental period suggests that early detection and aggressive management may improve prognosis in patients with CNS leptomeningeal dissemination of HB.
Subject(s)
Hemangioblastoma/pathology , Meningeal Neoplasms/secondary , von Hippel-Lindau Disease/pathology , Adult , Female , Hemangioblastoma/surgery , Humans , Male , Middle Aged , von Hippel-Lindau Disease/surgeryABSTRACT
Altered hepatic lipogenesis is associated with metabolic diseases such as obesity and hepatosteatosis. Insulin resistance and compensatory hyperinsulinaemia are key drivers of these metabolic imbalances. Fas apoptosis inhibitory molecule (FAIM), a ubiquitously expressed antiapoptotic protein, functions as a mediator of Akt signalling. Since Akt acts at a nodal point in insulin signalling, we hypothesize that FAIM may be involved in energy metabolism. In the current study, C57BL/6 wild-type (WT) and FAIM-knockout (FAIM-KO) male mice were fed with normal chow diet and body weight changes were monitored. Energy expenditure, substrate utilization and physical activities were analysed using a metabolic cage. Liver, pancreas and adipose tissue were subjected to histological examination. Serum glucose and insulin levels and lipid profiles were determined by biochemical assays. Changes in components of the insulin signalling pathway in FAIM-KO mice were examined by immunoblots. We found that FAIM-KO mice developed spontaneous non-hyperphagic obesity accompanied by hepatosteatosis, adipocyte hypertrophy, dyslipidaemia, hyperglycaemia and hyperinsulinaemia. In FAIM-KO liver, lipogenesis was elevated as indicated by increased fatty acid synthesis and SREBP-1 and SREBP-2 activation. Notably, protein expression of insulin receptor beta was markedly reduced in insulin target organs of FAIM-KO mice. Akt phosphorylation was also lower in FAIM-KO liver and adipose tissue as compared with WT controls. In addition, phosphorylation of insulin receptor substrate-1 and Akt2 in response to insulin treatment in isolated FAIM-KO hepatocytes was also markedly attenuated. Altogether, our data indicate that FAIM is a novel regulator of insulin signalling and plays an essential role in energy homoeostasis. These findings may shed light on the pathogenesis of obesity and hepatosteatosis.
Subject(s)
Apoptosis Regulatory Proteins/deficiency , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/metabolism , Animals , Energy Metabolism , Female , Humans , Insulin/metabolism , Lipogenesis , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle AgedABSTRACT
AIM: To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. METHODS: A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. RESULTS: Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c , blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. CONCLUSIONS: Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.
Subject(s)
Asian People/statistics & numerical data , Cardiovascular Diseases , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/mortality , Health Status Disparities , Kidney Failure, Chronic , Adult , Aged , Cardiovascular Diseases/ethnology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Cause of Death , Diabetic Nephropathies/complications , Diabetic Nephropathies/ethnology , Diabetic Nephropathies/mortality , Ethnicity/statistics & numerical data , Female , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/ethnology , Kidney Failure, Chronic/mortality , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND AND PURPOSE: Dipeptidyl peptidase 4 (DPP4) is an aminopeptidase that is widely expressed in different cell types. Recent studies suggested that DPP4 plays an important role in tumour progression in several human malignancies. Here we have examined the mechanisms by which up-regulation of DPP4 expression causes epithelial transformation and mammary tumourigenesis. EXPERIMENTAL APPROACH: Expression of DPP4 and the peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1), and the cytotoxic effects of combined treatment with sitagliptin and juglone were investigated by immunohistochemistry, immunoblotting, real-time PCR, TUNEL and soft agar assays, using MCF7 cells. The effects of sitagliptin on tumour development in vivo were studied in the syngeneic 4T1 metastatic breast cancer model. KEY RESULTS: Activity of the transcription factor E2F1 induced by EGF was enhanced by DPP4, thus increasing PIN1 expression. Furthermore, DPP4 enhanced MEK/ERK and JNK/c-Jun signalling induced by EGF, inducing AP-1 activity and epithelial cell transformation. In contrast, DPP4 silencing or DPP4 inhibition in MCF7 cells inhibited PIN1 expression via E2F1 activity induced by EGF, decreasing colony formation and inducing DNA fragmentation. In the syngeneic 4T1 metastatic breast cancer model, DPP4 overexpression increased tumour development, whereas treatment with sitagliptin and/or juglone suppressed it. Consistent with these observations, DPP4 levels were positively correlated with PIN1 expression in human breast cancer. CONCLUSIONS AND IMPLICATIONS: DPP4 promoted EGF-induced epithelial cell transformation and mammary tumourigenesis via induction of PIN1 expression, suggesting that sitagliptin targeting of DPP4 could be a treatment strategy in patients with breast cancer.