Day 2 :
Keynote Forum
Mikhail G Kolonin
University of Texas, USA
Keynote: Controlling adipose tissue metabolism by targeting white and brown preadipocytes
Biography:
Mikhail G Kolonin is an Associate Professor and Director of the Center for Metabolic and Degenerative Diseases at the University of Texas in Houston. As a PhD from
Wayne State University, he pioneered the concept of expressing peptides disrupting protein interactions in animals. As a Postdoctoral fellow at MD Anderson Cancer Center, he screened combinatorial libraries to identify druggable cell surface markers. Based on this approach, he has invented experimental therapeutics for obesity and cancer. He is an Author of over 60 publications, and has editorial positions with Molecular Carcinogenesis and Cancer Research. He is endowed with a Distinguished University Chair in Metabolic Disease Research.
Abstract:
Changes in the relative abundance of thermogenic beige adipocytes and lipid-storing white adipocytes in adipose tissue underlie the progression of obesity and metabolic disease. We have discovered that mouse and human adipose tissue contains distinct beige and white adipocyte progenitor populations marked by PDGFRα or PDGFRβ expression, respectively. Our recent report suggests that adipocyte lineage specification and metabolism can be modulated through PDGFR signaling. We have also developed hunter-killer peptides, composed of a cell surface receptor-binding domain and a pro-apoptotic domain, for targeted ablation of cells in adipose tissue. A hunter-killer peptide D-WAT, targeting PDGFRβ+ white adipocyte progenitors, suppresses high fat diet-induced obesity development and enabled maintenance of active metabolism. Another compound, adipotide, targeting endothelial cells and adipocytes in white fat, reverses obesity in several animal models and has shown promise in a clinical trial. In unpublished studies, we have developed a hunter-killer compound D-BAT, based on a peptide that targets brown fat tissue, which may relieve hypermetabolic conditions. New experimental approaches to fat tissue composition and function control will be discussed.
Keynote Forum
Gerald C Hsu
eclaireMD Foundation, USA
Keynote: A case study of the relationship between weight and glucose using math-physics medicine
Biography:
Gerald C Hsu received an honourable PhD in mathematics and majored in engineering at MIT. He attended different universities over 17 years and studied seven academic disciplines. He has spent 20,000 hours in T2D research. First, he studied six metabolic diseases and food nutrition during 2010-2013, then conducted research during 2014-2018. His approach is “math-physics and quantitative medicine” based on mathematics, physics, engineering modelling, signal processing, computer science, big data analytics, statistics, machine learning, and AI. His main focus is on preventive medicine using prediction tools. He believes that the better the prediction, the more control you have.
Abstract:
Background & Aim: During a period of 2,245 days (1/1/2012 - 2/24/2018), the author, who has type 2 diabetes for approximately twenty years, collected and processed about 1.5 million biomedical data regarding his health and lifestyle conditions, including 13,470 data for weight and glucose. This dataset includes medication, weight (measured after waking up and at bedtime), FPG, PPG (3 times a day), carbs and sugar intake, exercise, stress, sleep, travel, weather, glucose measurement time delay, water intake, bowel movement, night time urination, etc. All of the above factors are interrelated with each other to a different degree since the human body is a highly nonlinear, dynamic, and sophisticated “analog” system. In this article, the author will discuss the direct relationship between weight and glucose, both FPG and PPG.
Material & Method: Weight is one of the outputs as well as one of the inputs of human metabolism system. Its main contribution factors are food consumption quantity, food quality (fat, protein, carbs, sugar), exercise amount, bowel and urine elimination, sleep quality, emotional stress, etc. Glucose (A1C, daily average glucose, FPG, PPG) involves about 20 direct and indirect input factors with 4 major factors, including medication, weight, carbs/sugar, and exercise. Prior to 2012, he did not keep a complete daily record of his health and lifestyle data. However, he weighed 210 lbs. / 95.5kg (BMI 31, obese), his peak PPG was 380 mg/ dL, average daily glucose was 280 mg/dL, and A1C above 10.0%. After 2012, he has kept a complete record. His weight bounced between 166.9 lbs. / 75.9 kg (BMI 24.65) and 193.8 lbs. / 88.1 kg (BMI 28.65); therefore, his averaged weight was 178 lbs. / 81 kg (BMI 26.28). His glucose level varied from 52 mg/dL to 280 mg/dL, average daily glucose was 126.5 mg/dL, and A1C around 6.5%. The author utilized advanced mathematics to develop various governing equations. He applied finite element engineering concept to convert a human analog system into a digitized system to get approximate solutions. He also decomposed a complicated glucose wave into many single-sourced waveforms and then recombine them to a predicted glucose wave signal for comparison between measured vs. predicted glucose. Each single-sourced waveform is further studied for its intensity and importance level of contribution to glucose formation. Finally, he applied many statistical techniques to analyze these massive data, including linear accuracy, correlation and determination coefficients, spatial analysis, time series, frequency-based analysis via Fourier and Hilbert Transforms, etc. He has spent 4 years researching and interpreting the outcomes from his numerical simulation work.
Results: There are approximately 10 direct influential factors and about another 10 indirect factors for determining our glucose level. For FPG, weight is the most dominant factor contributing 80% to 90% to its value. In the time series analysis, results show that, between weight and FPG, their correlation is 84% (high). In spatial analysis, results show 93% of the total collected data are covered by a +/- 20% band. This “relationship band” stretched from point A (24.5, 95) to point B (27.2, 150) on a spatial map with coordinates of x=BMI, y=glucose. However, for PPG, weight is not the dominating factor any more. Instead, combined carbs and sugar intake with exercise occupied about 81% of the contribution and importance level of PPG. Weather and measurement time delay count about 14% and the other factors count about 5%. In the time series analysis, results show that, between weight and PPG, their correlation is between 9% to 36% (low). In spatial analysis, results show 86% of total collected data are covered by a +/- 20% “horizontal” band which is centered around a “constant” PPG value of 127 mg/dL. A stacking spatial analysis graphics over6 years from 1/2012 through 2/2018 shows that his BMI moved toward the lower range, while his PPG kept at a relative constant level around 127 mg/dL.
Conclusion: Based on the case study of this overweight but not obese (BMI < 30) patient’s data analyses, results show that most of his FPG data (93%) are almost directly proportional to his weight change according to a “fixed” slope. However, most of his PPG data (86%) have been kept within a range of 102 mg/dL and 152 mg/dL. The amplitude changes within this range are mostly determined by both carbs / sugar and exercise, but not directly by weight.
Keynote Forum
S M Rajendran
Bharath University, India
Keynote: Third eye diabetes reversible/curable (scientific and holistic approach)
Biography:
S M Rajendran has his unique way in evaluation and passion in improving global health related to Diabetes Mellitus to the past three decades. He built this model, through his vast experience in research and academic activities. His main research Study is THIRD EYE and prevalence of diabetes in Born Blind Persons. He is an Adviser for Text Book of Clinical Medicine Editor by KUMAR and CLARK. At present he is working as a professor of Medicine and Diabetology at Vijaya Medical and Educational Trust, Chennai.
Abstract:
In spite of extensive research for the past five decades by us, we are yet to get a clear solution towards cure/reverse of diabetes. Where is the fault? Either physician, pharma, people or inadequate research or yet to understand the basics of β cell. The biggest question is who controls and why not regenerated unlike other cells. The β cell is situated in the center of our body, it balances the whole body cells and organs. The β cell is unique in character and does not possess any trophic hormones unlike other endocrine glands, moreover why β cell is not controlled by either pituitary or hypothalamus? Related to the above questions, author carried out a research to find out a probable answer. His study included 500 born-blind people with control group of same ages 35-50 years. Neither blind people nor controlled group has diabetes prior. The study reveals all the born-blind people having normal blood sugar without any evidence of either pre diabetes or diabetes, whereas, the control groups reveals 85% are having diabetes. This has opened his eyes towards holistic scientific approach. The literature reveals, MTNR1A, MTNR1B receptors present in the cell. The figure will explain So, when we sleep, the hormone melatonin will increase there by decreases the insulin secretion that leads to β cell to recover the function. Similarly, the meditation will open our third eye (Pineal Gland) and melatonin level will increase that will protect the β cell and it controls the blood sugar. In spite of lot of drugs, people in the world are unable to control the diabetes in our country. But in Tamil Nadu those who are on meditation and lifestyle adaptation, their diabetes status has come well under control within 6 months period. The meditation will release the desire, self-awareness and increase the will power, repairs the cells there by we obtain a healthy life, without any side effects or genetic damage.
- Diabetes Melitus Type 1| Diabetes Melitus Type 2 | Diabetes Research | Diabetic Disorders and Treatment | Diabetic Neuropathy
Location: Olimpica 2
Chair
Douglas N. Ishii
Colorado State University | USA
Co-Chair
Serge P. Bottari
University Grenoble Alpes | France
Session Introduction
Sara Lasker
Madison T1D Coach LLC | USA
Title: Type 1 Diabetes: Seeing the whole person
Time : 14:15-14:40
Biography:
Sara Lasker is one of the first MCHES, CDE's in the world! As a Certified Diabetes Educator (CDE) and Master Certified Health Education Specialist (MCHES) she works with people to become the diabetes expert of their type 1 diabetes by discovering the Occupational, Social, Spiritual, Intellectual, Physical, Emotional, and Environmental
balance.
Abstract:
There is a mind shift that needs to occur in the clinical world of diabetes management to stay relative. The shift is to listen to the patient; what they were wanting out of their life with diabetes, and what/who can help motivate them; patients want to be more involved, motivated, and guided to find solutions to manage their diabetes. The management of type 1 diabetes goes beyond the basics and dives into the balance of the occupational, social, spiritual, intellectual, physical, emotional, and environmental (OSSIPEE) factors to live happy, healthful lives with diabetes. To stay relevant in your practice, you must come explore OSSIPEE.
Anna Archvadze
Tbilisi State Medical University | Georgia
Title: Clinical and Pharmacological basis for the use of drugs inhibiting of the RAAS in patients with Diabetic Neuropathy
Time : 14:40-15:05
Biography:
Archvadze Anna S H has Over 8 years’ experience as a Medical Doctor working in different medical institutions. She has Over 15 years’ experience as a Trainer/Teacher of Medical Sciences. Over 11 years’ experience in health and Social project/program development, execution, monitoring and completion, Over 7 years’ experience in International Project Management working for the world bank financed health projects, Over 5 years’ experience in an assessment of training needs, design and elaboration of training programs, provision of trainings for emergency care medical staff and for healthcare service providers, Over 10 years of experience in supervision of the contract performance with medical institutions, pharmaceutical firms, governmental and non-governmental organizations.
Abstract:
Introduction: The incidence of diabetes and its complications is increasing to staggering proportions. In 2014 the WHO estimated an overall prevalence of 422 million (8.5%) individuals with diabetes mellitus (DM). The diabetic neuropathy (DNP) which is one of complication of DM (50%) comprises a heterogeneous group of disorders that can cause neuronal dysfunction
throughout the human body. The optimal therapy involves: blood glucose level control, anticonvulsants, antidepressants and opioid administration, though it does not change pathogenic pattern. The recent studies suggest that the renin angiotensin aldosterone system (RAAS) plays a vital role in regulating glucose metabolism and blood pressure. In the same time the metabolic abnormalities associated with diabetes lead to activation RAAS, which might promote the formation of reactive oxygen species to lead the neuronal dysfunctions. Furthermore, TNFα is part of the response of the organism to hypertension and is originally described as one of the central mediators of inflammation trough the activation of transcription factor NFκB.
Methodology: The study is going on in parallel groups. The patients (enrolled on randomized principle) with DNP will be investigated. Group I with DNP was treated by aliskiren and group II with the same pathology, proceeding with the treatment without aliskiren but given telmisartan, for certainty of aliskiren efficacy. At the start of the trial and on completion of the six weeks period TNFα level and C-peptide are determined.
Findings: Telmisartan has less TNFα modulatory effects than aliskiren, namely, the symptoms of neuropathy as well as blood TNFα level and C-peptide level are not changed significantly.
Conclusion & Significance: TNFα is involved in DNP pathogenesis formation and clinical manifestation. Aliskiren amelioratessymptoms in DNP patients by modulatory impact on TNFα, so we have results for clinical and pharmacological analysis ofaliskiren application in DNP. The involvements of RAAS system in developments of DNP need further clinical analysis.
Kyunglim Lee
Ewha Womans University | Korea
Title: Use of transnationally controlled tumor protein-derived protein transduction domain for improved intranasal delivery of insulin
Time : 15:05-15:30
Biography:
Kyunglim Lee received PhD degrees from Tufts University, MA, USA. She had Postdoctoral research training in Molecular and Cellular Biology, Harvard University. Since 1995, she has been with the College of Pharmacy, Ewha Womans University, where she is currently a Full Professor. Her main areas of research interest are pathophysiology of hypertension, allergy, and tumorigenesis caused by translationally controlled tumor protein. Currently, she serves as an Editorial Board Member of Scientific Reports and SM Journal of Nephrology and Therapeutics. She is a Member of the American Society for Biochemistry and Molecular Biology, Korean Society of Biochemistry and Molecular Biology, Korean Society for Molecular and Cellular Biology, Pharmaceutical Society of Korea.
Abstract:
Statement of the Problem: Insulin is given to patients with diabetes by subcutaneous injection. However, noninvasive intranasal administration is easier for patients requiring daily treatment. Protein transduction domains (PTDs) are recognized as promising vehicles for the delivery of macromolecular drugs. We have previously shown that a region in the N-terminus (residues 1–10) of translationally controlled tumor protein (TCTP) contains aPTD (TCTP-PTD), MIIYRDLISH, which can serve as a vehicle for the delivery of macromolecules into the cells and tissues. In the current study, we evaluated the potential and safety of TCTP-PTD and its mutant analogs as nasal absorption enhancers for delivery of insulin. The goal of the current study was to examine whether the co administration of a drug with TCTP-PTD or its mutant analogs, can efficiently deliver insulin into the nasal mucosal membranes of animals.
Methodology & Theoretical Orientation: We examined the degree to which insulin was absorbed in nasal mucosa and also if any mucosal damage occurs following such nasal delivery of insulin using TCTP-PTDs as a vehicle. The systemic delivery of insulin was assessed by measuring the changes in blood glucose levels after nasal co administration insulin and TCTP-PTDs.
Findings: Of the 4 TCTP-PTD analogs examined, TCTP-PTD 13 significantly enhanced the nasal absorption of insulin in normal mice as well as alloxan induced diabetic rats. The binding between the TCTP-PTD analog and insulin may enable the penetration of insulin through the nasal mucosa. Histological examination of mice and rat nasal mucosa 7 days after repeated nasal administration showed no evidence of toxicity at the site of nasal administration.
Conclusion & Significance: In this study using insulin as a test system we demonstrate that the TCTP-PTD analog offers a promising approach for nasal peptides and protein-drugs delivery.
Yoshihisa Sugimura
Fujita Health University | Japan
Title: Rabphilin-3A as a targeted autoantigen in lymphocytic infundibuloneurohypophysitis
Time : 15:30-15:55
Biography:
Yoshihisa Sugimura is currently working as Professor in the Division of Endocrinology and Metabolism, Department of Internal Medicine at Fujita Health University, Japan. He did his PhD at Nagoya University Graduate School of Medicine, Japan and he joined as an Assistant Professor in the same university. His main research interest is in endocrinology, diabetes, neuroendocrinology, water, sodium metabolism and hypernatremia vasopressin.
Abstract:
Central diabetes insipidus (CDI) can be caused by several diseases, but in about half of the patients the etiological diagnosis remains unknown. Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among idiopathic CDI; however, the differential diagnosis from other pituitary diseases including tumors can be difficult due to similar clinical manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy. The study was designed to identify the autoantigen(s) in LINH and thus develop a diagnostic test based on serum autoantibodies. Rabphilin-3A proved the most
diagnostically useful autoantigen. Anti-rabphilin-3A antibodies were detected in 22 of the 29 (76%) patients (including 4 of the 4 biopsy-proven samples) with LINH. In contrast, these antibodies were absent in patients with biopsy-proven sellar/ suprasellar masses without lymphocytic hypophysitis (n=34), including 18 patients with CDI. Rabphilin-3A was expressed in posterior pituitary and hypothalamic vasopressin neurons but not anterior pituitary. In conclusion, these results suggest that rabphilin-3A is a major autoantigen in LINH. Autoantibodies to rabphilin-3A may serve as a biomarker for the diagnosis of LINH, and be useful for the differential diagnosis in patients with CDI.
Sungmun Lee
Khalifa University of Science and Technology | UAE
Title: Inhibition of amylin aggregation and cytotoxicity to β-cells by acids
Time : 16:10-16:35
Biography:
Sungmun Lee is currently working as an Assistant Professor in Khalifa University. He completed his Ph.D. in Texas A&M University, USA. His main research interest is in Development of Novel Drug Delivery System, Cardiovascular Diseases, Diabetes, Alzheimer's disease and Inflammatory Diseases. He has focused on the development of novel drugs and drug delivery systems for treating inflammatory diseases such as diabetes, Alzheimer’s disease, and cardiovascular diseases.
Abstract:
Statement of the Problem: Protein aggregation is associated with more than 20 degenerative diseases. Fibrillar aggregates of Aβ, α-synuclein, and amylin are pathological features in Alzheimer’s disease, Parkinson’s disease, and type II diabetes respectively. Aggregation of amylin causes cytotoxicity to pancreatic β-cells. The purpose of this study is to investigate the effect of different types of acids on the aggregation of amylin and cytotoxicity of aggregates to β-cells.
Methodology & Theoretical Orientation: Amylin-(1-37) was purchased from Sigma-Aldrich. Amylin (15 μM) with or without different types of acids were incubated at 37oC and the amylin fibrils were measured by the thioflavin T (ThT) binding assay at indicated time points. For cytotoxicity test, RIN-m5f, pancreatic β-cells, was incubated in a amylin (15 μM) with or without different types of acids. After 24 h, Thiazolyl blue tetrazolium bromide (MTT) was added to cells and the absorbance of live cells was measured at 570 nm.
Findings: Six acidic small molecules were screened in terms of their ability to inhibit amylin aggregation using ThT assay. Among six acids, two acids, lipoic acid and ascorbic acid, showed highest attenuation in ThT fluorescence intensity of 57.9±17.2% and 57.1±12.8%, compared to amylin (15μM) only. To further assess the cytotoxicity of amylin aggregates with or without two acids, MTT assay was performed using pancreatic RIN-m5f β-cells. Pre-formed fibrillar amylin only caused the cytotoxicity of 67% as compared to freshly prepared monomeric amylin. The addition of two acids to amylin decreased the
cytotoxicity to 44% and 49% respectively. Molecular modeling demonstrated that lipoic acid and ascorbic acid interact with amylin via hydrophobic interactions.
Conclusion & Significance: Lipoic acid and ascorbic acid can bind to amylin via hydrophobic interaction, which inhibits orslows down the aggregation of amylin and the toxicity of amylin aggregates to RIN-m5f, pancreatic β-cells.
Alla Ovsyannikova
IIPM-ICG SB RAS | Russia
Title: The prevalence of dyslipidemia in patients with different types of MODY diabetes
Time : 16:35-17:00
Biography:
Alla Ovsyannikova finished Novosibirsk Medical University, Russia in 2008 year with Honors. She had two certificates of specialists in Internal Medicine and Endocrinologist. She is a PhD since 2013 with dissertation work "Diabetes mellitus in young people: Some clinical and molecular genetic aspects". Currently, she is working as an Endocrinologist and Scientist in IIPM-Branch of IC&G SB RAS. Her research work is about monogenic types of diabetes mellitus (especially MODY diabetes) in young patients. She investigates the characteristics of the clinical course, treatment and genetic features in Siberian and Russian population. She has published more than 20 abstracts in national refereed journals, 30 abstracts in conference with international participation. She has participated in international conferences.
Abstract:
Aim: The purpose of the research was to determine and compare the prevalence of dyslipidemia in patients with different types of maturity onset diabetes of the young (MODY).
Materials & Methods: Diagnosis of MODY was verified in 37 patients on the basis of direct automatic sequencing and sequencing by Sanger genes, mutations in which lead to the development of MODY 1-13 diabetes. This group consisted of 21 patients with GCK-MODY (MODY2), 9 with HNF1A-MODY (MODY3), 1 with HNF1B-MODY (MODY5), 1 with NEUROD1-MODY (MODY6), 2 with CEL-MODY (MODY8), 3 with ABCC8-MODY (MODY12).
Results: The group of patients with MODY diabetes is comprised by 37 people: 23 females (62.2%), 14 (37.8%) males (p=0.934). The median age of the patients was 29.1 (0; 70) years, the median age of diagnosis of diabetes mellitus was 25 (0; 45) years, the median duration was 3.2 (0; 35) years. All patients had a normal body mass index. The median level of total cholesterol was 4.9 (3.4; 7.1) mmol/L, LDL- 2.9 (1.6; 4.5) mmol/L, HDL - 1.3 (1.0; 2.4) mmol/L, triglycerides - 1.0 (0.5; 3.1) mmol/L. Elevated LDL was diagnosed in 10 patients (27.0%) and hypertriglyceridemia in 6 patients (18.8%). The HNF1A gene (MODY3) encodes one of the transcription factors that regulates the expression of genes associated with lipid and carbohydrate metabolism. Therefore, it is this type of MODY associated with the dyslipidemia which leads to early macrovascular complications. In this study 4 out of 9 (44.4%) patients with HNF1A-MODY had an elevated level of LDL and 2 (22.2%) hypertriglyceridemia. In patients with GCK-MODY, an increase in LDL was detected in 3 patients (14.3%, pMODY2-MODY3 = 0.209), hypertriglyceridemia in 2 (12.5%, pMODY2-MODY3 = 0.533).
Conclusions: Dyslipidemia is determined in 27% in young patients with MODY diabetes with a short duration of diabetes mellitus and a lack of obesity which indicates the need for prescribing therapy to prevent macrovascular complications. There were no significant differences in lipid levels in patients with HNF1A-MODY and GCK-MODY in the Siberian region.
Acknowledgement: The research work was suppotted by RSF project N14-15-00496-P
Alla Ovsyannikova
IIPM-ICG SB RAS | Russia
Title: Description of the clinical case of the patient HNF1A (MODY3) with familial segregation of the disease in five generations
Time : 17:00-17:25
Biography:
Alla Ovsyannikova finished Novosibirsk Medical University, Russia in 2008 year with Honors. She had two certificates of specialists in Internal Medicine and Endocrinologist. She is a PhD since 2013 with dissertation work "Diabetes mellitus in young people: some clinical and molecular genetic aspects". Currently, she is working as an Endocrinologist and Scientist in IIPM-Branch of IC&G SB RAS. Her research work is about monogenic types of diabetes mellitus (especially MODY diabetes) in young patients. She investigates the characteristics of the clinical course, treatment and genetic features in Siberian and Russian population. She has published more than 20 abstracts in national refereed journals, 30 abstracts in conference with international participation. She has participated in international conferences.
Abstract:
Aim: The purpose of the research was to determine family segregation in a proband family with a confirmed mutation in the HNF1A gene (MODY3 diabetes).
Materials & Methods: The diagnosis of HNF1A-MODY was verified by the proband and his relatives on the basis of direct automatic sequencing and sequencing by Sanger.
Results: Proband - a woman of 50 years, gestational diabetes mellitus (DM) is diagnosed at the age of 21 during pregnancy, insulin therapy was done in the basis-bolus regimen. After delivery insulin therapy was canceled, the patient had a strict diet. Decompensation of carbohydrate metabolism was at the age of 28 years on the background of stress, insulin therapy was prescribed in the basal-bolus regimen, which is still preserved. Non proliferative diabetic retinopathy, peripheral neuropathy, dyslipidemia were defined. Antibodies to B-cells and glutamate decarboxylase were negative and the C-peptide was slightly reduced. DM was at the great-grandfather, the grandmother from 65 years, mother of the proband from 45 years, at the son from 21 years. Mother and son of the proband had dyslipidemia with increased cholesterol of low density lipoproteins, in grandmothers and great grandfathers- macrovascular complications (acute cerebrovascular accident) at a late age. A previously unrecognized mutation in the 1 exon of the HNF1A gene in a proband, her mother and her son was revealed according to molecular genetic research. An identical mutation was detected in the granddaughter of a proband at the age of 2 months.
Conclusions: The pedigree of HNF1A-MODY demonstrates the phenomenon of genetic prediction that is the gradual decrease in the age of diagnosis in subsequent generations probably due to increased awareness leading to earlier testing of glucose levels.
The decrease in the age of development of dyslipidemia in patients with a mutation in the HNF1A gene was also determined which may be interrelated characteristics and require further study.
Acknowledgement: The research work was suppotted by RSF project N14-15-00496-P
Jishi Liu
Third Xiangya Hospital of Central South University
Title: Protective effects of Vit D/VDR on renal autophagy in early stage of 12-weeks diabetic mice induced by STZ
Biography:
Jishi Liu is working as an associate professor in Third Xiangya Hospital of Central South University in Changsha City, China. Her main research area is in prevention and treatment of acute and chronic kidney disease, the clinical and basic research of IgA nephrology. She received three funding support. Headed over 1 NSFC of China, 2 Hunan provincial natural science fund subject, and published 24 SCI papers.
Abstract:
Background: Autophagy is an important cause of diabetic nephropathy (DN). We found that the expression of nuclear transcription factor VDR in renal tubule epithelium was down-regulated and negatively correlated with urinary albumin and inflammation in DN patients, while intestinal disease and tumor related studies suggested that vitamin D receptor (VDR) could regulate autophagy. Therefore, we studied the relationship between Vit D/VDR and renal autophagy in early stage of 12 weeks diabetic mice induced by STZ.
Methods: In order to investigate the potential regulation of VDR on autophagy in renal cells, we established streptozotocin (STZ) induced diabetic nephropathy model on VDR knockout mice and wild type mice. Then we used VDR agonist paricalcitol to interfere with wild-type mice induced by STZ. The autophagy related indexes, such as LC3II/I, ATG16L1, P62, inflammation and fibrosis level were measured at 12 weeks in the renal cortex of mice.
Results: Results of immunohistochemistry and western blot showed that the level of LC3II/I, ATG16L1, FN and collage were clearly lower in renal tissue of non-diabetic VDR knockout rats than those of the wild type. Level of those indexes also lower in STZ induced diabetic VDR knockout mice than in wild-type mice. Expression of P62 in diabetic VDR knockout mice induced by STZ was significantly higher than that in wild-type DN mice and VDR knockout mice. Paricalcitol could up-regulate LC3II/I protein and ATG16L1mRNA and inhibit the accumulation of P62 protein in wild-type DN mice, but did not inhibit the expression of P62 mRNA.
Conclusion: VDR is involved in the regulation of autophagy in early stage of diabetic nephropathy. Paricalcitol may play a protective role in renal autophagy activation in early stage of diabetic mice induced by STZ through up-regulating ATG16L1 and promoting the degradation of P62.
- Diabetes Research in Clinical Practice | Stem Cell treatment in Diabetes | Diabetes Medication & Therapy | Diabetes & Metabolic Syndrome | Diabetes Melitus | Endocrinology & Diabetes: Diseases & Disorders
Location: Olimpica 2
Session Introduction
Yana Bai
Lanzhou University | China
Title: Metal exposure and risk of diabetes in the Jinchang cohort
Biography:
Yana Bai has established the Jinchang cohort in China, as the largest multi-metal exposure cohort in the world, who is mainly engaged in the research of prevention and treatment strategies and measures for diabetes and cancer. The risk factors, etiology, pathogenesis, early diagnosis and evaluation of intervention effect of diabetes and tumor were carried out through Jinchang cohort.
Abstract:
Statement of the Problem: With the global environment change, people begin to pay close attention to the correlationship between the heavy metals of environmental pollution and the development of T2DM. The research is to estimate the relationship on heavy exposure and T2DM , and to investigate the association between multiple metals exposure and dysregulation of glucose homeostasis on Jinchang cohort.
Methodology & Theoretical Orientation: In 2011-2013, we established Jinchang cohort including 47,998 participants in china. Logistic regression was used to study the association between three occupational groups categorized according to the likely metal exposure levels and risk of these diseases. Urinary arsenic, cadmium, cobalt, copper, nickel and zinc of 464 occupational workers in Jinchang cohort were detected by inductively coupled plasma quadruple mass spectrometry (ICPMS). Logistic regression model was used to evaluate the association of metal exposure with high-FPG (≥ 75th percentile) and risk of dysglycemia (diabetes and impaired fasting glucose).
Findings: The overall prevalence of diabetes and prediabetes was 7.5% and 16.8%, respectively. The adjusted odds ratios (95% CI) for diabetes among mining/production workers and smelting/refining workers were 1.5 (1.3-1.7) and 3.8 (3.4-4.3), respectively, compared to office workers. Increasing levels of uninary Ni and Zn were both positively associated with risk of high-FPG and dysglycimia (Ptrend = 0.004 for Ni and Ptrend = 0.01 for Zn). The J-shaped dose-response realtionships between urinary Ni (P non-linearity= 0.03) and Zn (P non-linearity < 0.001) with FPG were also observed.
Conclusion & Significance: Occupations associated with higher levels of metal exposure were associated with an increased risk of diabetes in Jinchang cohort. Multiple urinary metals, particularly zinc and nickel were positively associated with elevated blood glucose and dysglycemia.
Key words: Metal exposure, Diabetes mellitus, Fasting blood glucose, Dysglycemia, Association
Caina Li
Peking Union Medical College | China
Title: A completely novel long-acting GLP-1 receptor agonist, Glutazumab
Time : 12:00-12:25
Biography:
Caina Li has been engaged in anti-diabetic pharmacology since graduation in 2011. She mainly worked on the pharmacological study of novel GLP-1-based drugs and study mechanism of the occurrence and development of diabetes. Till now, she has completed the pharmacological studies of 3 novel long-acting GLP-1 receptor agonists, Natural Science Foundation of China project and New Teacher Doctoral Fund of Ministry of Education of China. She also created a method for evaluating the gastric emptying in mice based on the diazo reaction, which could significantly reduce the use of animals in the evaluation of gastric emptying.
Abstract:
GLP-1-based drugs have been proposed as a mono- or combined therapy for type 2 diabetes mellitus for the outstanding features, but natural GLP-1 is hardly used in clinic due to its short half-life, while short-acting analogs/receptor agonists have poor compliance in patients for frequent dosing. This study aims to introduce a novel long-acting GLP-1 receptor agonist,
which is an antibody fusion protein by linking the human GLP-1 derivative to a humanized GLP-1R antibody via a peptide linker, and to evaluate its anti-diabetic effects and duration. Glutazumab is characterized by receptor binding and reporter gene assay, and its specificity was investigated through addition of exendin (9-39) and Ab1 which were the cognate receptor antagonist and antibody respectively. To evaluate the anti-diabetic effects, glutazumab was studied in diabetic KKAy mice by single dose and repeated doses. The blood glucose, food/water intake, body weight and gastric emptying was measured in
the single dose study, while blood glucose, GSP, HbA1c, insulin and lipid were determined in the repeated-dose study. The oral glucose tolerance and hyperglycemic clamp test were performed to assess the β-cell function. In all the experiments, dulaglutide served as a control. Glutazumab significantly binds and activates GLP-1R, while the natural receptor antagonist exendin (9-39) showed no inhibition except in the presence of the antibody Ab1. Single injection of Glutazumab remarkably decreased blood glucose for 3~6 days in normal ICR mice and diabetic KKAy mice. Repeated injections of glutazumab also evidently reduced non-fasting and fasting blood glucose fluctuation, decreased GSP and HbA1c levels, improved impaired oral glucose tolerance and β-cell function and ameliorated the dyslipidemia in diabetic KKAy mice. These results demonstrated that glutazumab is a novel long-acting GLP-1 receptor agonist with excellent anti-diabetic effect in KKAy mice, and suggested thatit may be a potential treatment for type 2 diabetes.
Yi Huan
Peking Union Medical College | China
Title: Discovery of GPR119/DPP4 dual-target compounds as anti-diabetic candidates
Biography:
Yi Huan has her expertise in discovery and development of novel anti-diabetic drugs. She established a variety of pharmacological methods and technologies to screen compounds, evaluate the activities of anti-diabetic agents. Now she is focusing on the discovery of novel anti-diabetic candidates, such as SGLT2 inhibitors, GPR119/40/120 agonists, FXR agonists and selective PPAR activators. Some of the anti-diabetic candidates she found have been developed into pre-clinical research up to date. She is nterested in pharmacological mechanism research and devotes into elucidation of the anti-diabetic effect of new drugs.
Abstract:
Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining β-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we designed and synthesized a series of xanthine derivatives as potent dual ligands targeting DPP-IV and GPR119 through an approach of the merged pharmacophores of GPR119 agonists and DPP-IV inhibitor linagliptin. Among these derivatives, we validate a compound, HBK001 which can both inhibit DPP4 and activate
GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse primary islets in a concentration-dependent manner. A single administration of HBK001 in ICR mice can increase plasma incretins (GLP-1 and GIP) levels much more efficiently than DPP4 inhibitor linagliptin. Long-term treatment of HBK001 in KKAy mice can
ameliorate hyperglycemia as well as improve glucose tolerance, while linagliptin fails to achieve such glucose-lowing effects despite inhibiting 95% of serum DPP4 activity. Furthermore, HBK001 can improve islet morphology in diabetic KKAy mice, increase β-cell mass by promoting proliferation and up-regulating genes involved in β-cell proliferation and function. Thus, we have identified, designed and synthesized a novel GPR119/DPP4 dual-target compound, HBK001, which represents a promising therapeutic candidate for type 2 diabetes, especially for patients who are insensitive to current DPP4 inhibitors..
Alaa Abdelkarim
ACE Cells Lab | UK
Title: ACE factor deficiency theory & its application in diabetes mellitus type II
Time : 13:50-14:15
Biography:
Alaa Abdelkarim has 27 years’ experience in the field of Endocrinology, Diabetes Mellitus and Cellular Therapy. He graduated from Cairo University Medical School and joined several overseas posts in the fields of Endocrinology and Diabetes with main focus on treating diabetes complications and using the cellular therapy in controlling the damage. Reverse the damage is the main title of his China-German joint research project. One big scientific project resulted in more than 80 patents in 2016.
Abstract:
There are more than 300 theories that explain aging and anti-aging. Most of the Chinese medicine doctors and the homeopathic doctors created theories, and each according to their own vision and experience. Some theories were created
to promote certain products and some were only to get some fame. On the other hand, the western medicine focused more on the pathogenesis and explanation of the diseases. The etiology occupied the main portion of their researches that explain the diseases and try to find their cures. No doubt, it is very important to know the etiology and to use it to be able to get the proper treatment. Imagine a city that was subjected to three different types of catastrophes, an earthquake, a tornado and a typhoon. The objective here is to rebuild this city and to restore its function. Knowing the general cause of the destruction will help us to take the proper damage control, but we can’t rebuild it depending only on damage control. For example, if the cause of destruction is nuclear bomb, then continuous survey for the irradiations will help in preventing lots of side of effects in the future, but eventually we need to rebuild the buildings and pave the roads and restore the infrastructure regardless of what type of bomb it. The cause of the destruction may help in the fine adjustment of the process of rebuilding, but not the general plan of restoring an entire city to its former glory. When it comes to the general reconstruction plan, there are two types. The first would be a slow but steady plan, in which we provide a systematic reconstruction plan build on small number of resources over a long period of time. The second plan is to provide a massive amount of resources over a condensed period of time. The first case is risky because the fewer resources one might have the more risk of delay one might get if any resource became faulty. In the second case there would be rapidly expanding renovation and there might be excess in resources once everything is restored based on my observations, i noticed the second case happening when it comes to using the peptides and cell therapy applications in either treating diseases or rejuvenation. Diabetes mellitus type II, we have multi-level complex destruction of the cells. Either on the level of B cells in the pancreas or the receptors in the target organs. In this lecture, we discuss the process of repair of B cells and how adjusting the level of regeneration can affect the HbA1c levels.
John A Monro
Massey University | New Zeland
Title: Glycaemic suppression by fruit residues
Time : 14:15-14:40
Biography:
John A Monro is a Principal Scientist at the New Zealand Institute for Plant & amp; Food Research Limited, and a Principal Investigator at the Riddet Institute, Palmerston North, New Zealand. His original research was on the structure and function of plant cell walls, but soon progressed to the role of cell walls, as dietary fibre, in gut function and health. He has researched dietary fibre in the fore and hind gut, how to measure it in a physiologically valid way, and how to communicate its effects to consumers so as to provide an accurate guide to food choices for health. More recently his research has focused on digestible carbohydrates in foods, on valid determination of carbohydrate availability by in vitro digestive analysis, and on food structural factors determining the glycaemic response to foods. He has also been concerned with the problem of communicating the relative glycaemic potency of foods to consumers and developed the concept of glycaemic glucose equivalents as a functional food value, to enable food composition databases to say not only what a food is, but also, what it does. At present he is conducting both postprandial and long term clinical trials on the benefits of fruit consumption in diets for glucose-intolerant consumers.
Abstract:
The glycaemic response to ingested carbohydrate foods is governed partly by gut-level processes of digestion that may be affected by digestion-resistant food remnants. Such processes include gastric emptying, luminal mixing, diffusion,
and enzymic depolarisation. Freed from the constraint of fruit structure, after in vitro digestion of kiwi fruit flesh the settled volume of dispersed kiwifruit debris was four times the flesh volume before digesting, and enough to occupy a large proportion of the free space within the foregut. The impact of kiwifruit remnants on gut processes involved in the glycaemic response to co-ingested carbohydrate foods was tested in vitro by measuring glucose diffusion, mixing, and pancreatic digestion of carbohydrate staples within the settled dispersion of kiwifruit remnants. The additional effect of introduced hydrocolloid on
mixing in the presence of kiwi fruit remnants was also measured. Within the settled dispersion of kiwifruit debris glucose diffusion was reduced by about 40%, simulated intraluminal mixing was reduced by about 50%, and digestion was retarded. Hydrocolloid substantially accentuated the retardation of mixing by kiwifruit remnants. In a subsequent clinical trial meals were formulated to be equal in carbohydrate content and type, but contain cereal plus kiwifruit, or cereal plus kiwifruit sugars, so any differences in meal effects could be attributed to non-available carbohydrate components of the kiwifruit. The meals containing kiwifruit suppressed the glycaemic response to co-ingested wheaten cereal, averted hyperglycaemia, and maintained satiety. The results suggest that dietary fibre from kiwifruit may significantly suppress the glycaemic response to co-ingested carbohydrate through its effects on physical processes in the gut that are part of digestion, and indicate a need for further research to clarify its role.
Suman Mishra
Massey University | New Zeland
Title: Timing of fruit ingestion and blood glucose response
Time : 14:40-15:05
Biography:
Suman Mishra started her scientific career at the University of the South Pacific (Fiji), before moving to New Zealand where she completed her PhD studies. She currently works at the New Zealand Institute for Plant and Food Research where she leads Carbohydrate Digestion and Metabolism Team. Her initial research was on in vitro digestion of carbohydrate foods and now works in the glycaemic response area and human trials.
Abstract:
Partial equal carbohydrate substitution of kiwifruit sugars for starch in foods co-ingested with whole kiwifruit (KF) leads to a substantial reduction in glycaemic response. The reduction in response appears to be due to both the exchange of fructose for glucose, and to the physical influence of undigested KF remnants on digestive processes in the foregut. As fructose consumption has been reported to promote blood glucose disposal, and KF remnants appear to retard processes that mediate absorption of starch-derived glucose from the foregut, it is possible that the ability of digestion-resistant remnants of kiwifruit
to modulate the glycaemic response to starchy food depends on the temporal proximity of the ingestion of KF and starchy staple. To test this dependence of interaction on the closeness of intakes, KF (200 g = flesh of two KF) was ingested 10 h, 90 min, 30 min before, at the same time as, or 30 min after a starch-based wheaten biscuit (WB) containing the same amount of available carbohydrate, mainly starch, as the KF. Capillary blood glucose concentrations and satiety were measured after ingestion of the foods. Partial substitution of WB by KF caused a 20–30% reduction in total glycaemic response irrespective
of the separation of KF and WB ingestion. However, ingesting KF 30 min before WB decapitated the blood glucose spike, whereas the reverse, WB ingested 30 min before KF, did not. The results suggest that both the temporal distribution of available carbohydrate (meal slowness) and differences in the composition of foods consumed at different stages in a meal may affect glycaemic response, perhaps by exerting different degrees of delay in the release of available carbohydrate from the stomach to small intestine during digestion.
Selen Yilmaz Isikhan
Hacettepe University | Turkey
Title: Assessment of zinc and copper levels in Diabetes Mellitus
Time : 15:05-15:30
Biography:
Selen Yilmaz Isikhan carried out an integrated master and doctorate education in biostatistics department of Hacettepe University Faculty of Medicine. She has been working as a lecturer at the same university since 2010. Her research interests are biostatistics, data mining, multivariate statistical analysis, high-dimensional bioinformatics studies and microbiota studies.
Abstract:
Statement of the Problem: The associations of serum zinc, copper and Zn/Cu ratio with clinical/biochemical characteristics in both types of diabetic patients were explored in this study.
Methodology & Theoretical Orientation: Serum levels of zinc and copper were measured by atomic absorption spectrophotometer in 26 type 1 and 80 type 2 diabetic patients, along with 205 age/gender-matched healthy controls.
Findings: Significantly decreased levels of Zn and Zn/Cu ratio were observed in both types of diabetic patients compared to controls, more clearly in type 1 (p<0.001). Positive and significant correlations between Zn and age (r=0.460, p<0.001), Zn and BMI (r=0.344, p<0.001), Zn/Cu and total cholesterol (r=0.207, p=0.033), and Zn and the number of coronary risk factors (Spearman’s r=0.311, p=0.001) were found. No significant relationship between Zn, Cu and Zn/Cu ratios with other biochemical parameters including HbA1c and in terms of family history, smoking, medications, micro vascular and macrovascular complications was found in both types of diabetic patients.
Conclusion & Significance: Alterations of trace elements have been reported to have effects on the pathogenesis and progression of diabetes mellitus. Although decreased Zn/Cu ratio was found in our diabetic patients, no significant correlations were observed with clinical/biochemical characteristics except BMI, cholesterol, total cholesterol, and the number of coronary risk factors in our patients. Further studies may be the final arbiter of this issue.
Hilal Zaid
Al-Qasemi Academic College | Israel
Title: Novel anti diabetic phytochemicals: isolation, protein target and mechanism of action
Time : 15:45-16:10
Biography:
Hilal Zaid is the Head of Alqasemi Educational Research Center, a former Head of the Sciences Teaching Department and a Senior Researcher in Biochemistry and Cell Biology at Al-Qasemi Academic College, Israel. He received his PhD in Biochemistry and Molecular Biology from the Ben-Gurion University, Israel on June 2005 and then was trained as a Postdoctoral Fellow at the Banting and Best Department of Medical Research, the University of Toronto. On 2006, he joined the Program in Cell Biology at the Hospital for Sick Children as a Postdoctoral Fellow until July 2008. He was recruited temporary at Ben-Gurion University as a Research Associate for 7 months. At the beginning of 2009 (until now), he established his own lab at Al-Qasemi Research Center, Al-Qasemi Academic College. He has over 85-refereed publications (35 journal articles, most of them in highly-rated journals; 1 book, 3 book chapters; 47 conference abstracts).
Abstract:
Nature is the best cooker of medicines due to the fact that natural products have been optimized to interact optimally with the biological systems through a long natural selection process. Natural products therefore have been a source of therapeutics for millennia, and during the past century, many drugs have been developed from natural sources. We have evaluated the anti-diabetic activity of the aerial parts (except when indicated) of several medicinal plants extracts in vitro namely: Abelmoschus esculentus L. (AE), Allium cepa (bulb, AC), Allium sativum (bulb, AS), Asparagus aphyllus L. (AA), Atriplex halimus (AH), Cinnamomon cassia (CC), Crataegus azarolus L. (CA), Gundelia tournefortii (GT), Nigella sativa (seeds, NS), Ocimum Basilicum (OB), Olea Europea (leaves, OE), Trigonella foenum-graecum (TF), Teucrium polium (TP) and Urtica dioica (UD). Water/ethanol, methanol, hexane and dichloromethane extracts were prepared from the above listed plants and the extracts toxicity and efficacy was tested in L6 muscle cells. Cytotoxic and anti-diabetic properties of the extract were evaluated also in vitro using L6-GLUT4myc muscle cells stably expressing myc epitope at the exofacial loop (GLUT4). GLUT4 translocation to the plasma membrane (PM) was elevated by up to 4 and 7 folds (-/+ insulin) after treatment with AA, AH, CV, GT, OB, TF, TP and UD for 20 h at none cytotoxic concentrations as measured with MTT and the LDH leakage assay. Sweet basil (OB) extracts were the most efficient in augmenting GLUT4 translocation to the PM. GC/MS phytochemical analysis
of GT, OB and TP methanol and hexane extracts revealed tens of compounds (some of them were detected for the first time by our group, Fig.1. These findings indicate that the observed anti diabetic properties of these plants are mediated, at least partially, through regulating GLUT4 translocation.
Muhammad Aneeq Haroon
Foundation University Medical College | Pakistan
Title: Utility of Albumin Creatinine Ratio (ACR) in monitoring diabetic retinopathy and nephropathy
Time : 16:10-16:35
Biography:
Muhammad Aneeq Haroon is a final year MBBS student at Foundation University Medical College, Islamabad. His main interest is specializing in Ophthalmology, Neurology and Pathology. His present research paper is on the topic of ‘Prevalence of migraine and tension type headache in medical students’ at 9th ANRD – Annual Neurology.
Abstract:
Statement of the Problem: Diabetic retinopathy and nephropathy are classified as microvascular complications of diabetes. Diabetic nephropathy (or diabetic kidney disease) is a progressive kidney disease caused by damage to the capillaries in the kidneys' glomeruli. It is characterized by nephrotic syndrome and diffuse scarring of the glomeruli. It is due to longstanding diabetes mellitus, and is a prime reason for dialysis in many developed countries. Diabetic retinopathy (DR) is a common vascular complication of diabetes, and a leading cause of sudden loss of vision. DR progresses from mild non-proliferative abnormalities to moderate and severe non-proliferative DR (NPDR), and to proliferative DR (PDR), which is characterized by gradual alterations in the retinal microvasculature leading to increased vascular permeability, retinal non perfusion, and pathological intraocular proliferation of retinal vessels. These complications are highly prevalent and place a significant burden on society if left untreated; therefore, early detection of DR and diabetic kidney disease (DKD) is important.
Objective: To evaluate albumin creatinine ratio (ACR) as a screening marker for detection of early diabetic retinopathy and nephropathy.
Methodology & Theoretical Orientation: This cross-sectional study was conducted in Combined Military Hospital, Multan from 15th January to 20th July 2017. A total of 386 patients were included in the study. They were known diabetics on treatment who reported for monitoring of diabetes and their urine protein was negative on dip strip. Informed consent was obtained from the patients and study was approved by the ethical review committee of the institution. 10 ml of random urine sample was collected in a clean container. Urinary albumin and creatinine were estimated by turbidimetric inhibition immunoassay and Jaffe kinetic reaction respectively, ACR was calculated as mg/mmol of creatinine. The statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software, version 23.
Findings: Total 386 diabetic patients were included in the study. Females were 38% while males were 62%. Minimum age was 34 years and maximum was 72 years with a mean age of 47±2.4 yrs. 6% patients were under the age of 40 years, 20% were between 40 to 50 years of age while 74% were more than 50 years of age. ACR levels were significantly different among the DR stages. ACR was <3mg/mmol in 74% patients indicating normal renal status and having no to mild-ok moderate NPDR, between 3-30 mg/mmol in 26% patients indicating micro albumin urea i.e. early diabetic nephropathy and having severe
NPDR and PDR.
Conclusion & Significance: In conclusion, the results of this study show that ACR level is associated with severity of DR and DKD. Therefore, normal-to-mildly increased albuminuria in diabetic patients should not be overlooked and requires close monitoring for early detection of complications.
Yana Bai
Lanzhou University | China
Title: Metal exposure and risk of diabetes in the Jinchang cohort
Time : 16:35-17:00
Biography:
Yana Bai has established the Jinchang cohort in China, as the largest multi-metal exposure cohort in the world, who is mainly engaged in the research of prevention and treatment strategies and measures for diabetes and cancer. The risk factors, etiology, pathogenesis, early diagnosis and evaluation of intervention effect of diabetes and tumor were carried out through Jinchang cohort.
Abstract:
Statement of the Problem: With the global environment change, people begin to pay close attention to the correlationship between the heavy metals of environmental pollution and the development of T2DM. The research is to estimate the relationship on heavy exposure and T2DM , and to investigate the association between multiple metals exposure and dysregulation of glucose homeostasis on Jinchang cohort.
Methodology & Theoretical Orientation: In 2011-2013, we established Jinchang cohort including 47,998 participants in china. Logistic regression was used to study the association between three occupational groups categorized according to the likely metal exposure levels and risk of these diseases. Urinary arsenic, cadmium, cobalt, copper, nickel and zinc of 464 occupational workers in Jinchang cohort were detected by inductively coupled plasma quadruple mass spectrometry (ICPMS). Logistic regression model was used to evaluate the association of metal exposure with high-FPG (≥ 75th percentile) and risk of dysglycemia (diabetes and impaired fasting glucose).
Findings: The overall prevalence of diabetes and prediabetes was 7.5% and 16.8%, respectively. The adjusted odds ratios (95% CI) for diabetes among mining/production workers and smelting/refining workers were 1.5 (1.3-1.7) and 3.8 (3.4-4.3), respectively, compared to office workers. Increasing levels of uninary Ni and Zn were both positively associated with risk of high-FPG and dysglycimia (Ptrend = 0.004 for Ni and Ptrend = 0.01 for Zn). The J-shaped dose-response realtionships between urinary Ni (P non-linearity= 0.03) and Zn (P non-linearity < 0.001) with FPG were also observed.
Conclusion & Significance: Occupations associated with higher levels of metal exposure were associated with an increased risk of diabetes in Jinchang cohort. Multiple urinary metals, particularly zinc and nickel were positively associated with elevated blood glucose and dysglycemia.
Key words: Metal exposure, Diabetes mellitus, Fasting blood glucose, Dysglycemia, Association