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      Cellular Contractility Profiles of Human Diabetic Corneal Stromal Cells

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          Abstract

          Diabetic keratopathy is a corneal complication of diabetes mellitus (DM). Patients with diabetic keratopathy are prone to developing corneal haze, scarring, recurrent erosions, and significant wound healing defects/delays. The purpose of this study was to determine the contractility profiles in the diabetic human corneal stromal cells and characterize their molecular signatures. Primary human corneal fibroblasts from healthy, Type 1 DM (T1DM), and Type 2 DM (T2DM) donors were cultured using an established 3D collagen gel model. We tracked, measured, and quantified the contractile footprint over 9 days and quantified the modulation of specific corneal/diabetes markers in the conditional media and cell lysates using western blot analysis. Human corneal fibroblasts (HCFs) exhibited delayed and decreased contractility compared to that from T1DMs and T2DMs. Compared to HCFs, T2DMs demonstrated an initial downregulation of collagen I (day 3), followed by a significant upregulation by day 9. Collagen V was significantly upregulated in both T1DMs and T2DMs based on basal secretion, when compared to HCFs. Cell lysates were upregulated in the myofibroblast-associated marker, α-smooth muscle actin, in T2DMs on day 9, corresponding to the significant increase in contractility rate observed at the same time point. Furthermore, our data demonstrated a significant upregulation in IGF-1 expression in T2DMs, when compared to HCFs and T1DMs, at day 9. T1DMs demonstrated significant downregulation of IGF-1 expression, when compared to HCFs. Overall, both T1DMs and T2DMs exhibited increased contractility associated with fibrotic phenotypes. These findings, and future studies, may contribute to better understanding of the pathobiology of diabetic keratopathy and ultimately the development of new therapeutic approaches.

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          Most cited references 57

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          IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030.

          Diabetes is an increasingly important condition globally and robust estimates of its prevalence are required for allocating resources. Data sources from 1980 to April 2011 were sought and characterised. The Analytic Hierarchy Process (AHP) was used to select the most appropriate study or studies for each country, and estimates for countries without data were modelled. A logistic regression model was used to generate smoothed age-specific estimates which were applied to UN population estimates for 2011. A total of 565 data sources were reviewed, of which 170 sources from 110 countries were selected. In 2011 there are 366 million people with diabetes, and this is expected to rise to 552 million by 2030. Most people with diabetes live in low- and middle-income countries, and these countries will also see the greatest increase over the next 19 years. This paper builds on previous IDF estimates and shows that the global diabetes epidemic continues to grow. Recent studies show that previous estimates have been very conservative. The new IDF estimates use a simple and transparent approach and are consistent with recent estimates from the Global Burden of Disease study. IDF estimates will be updated annually. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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            Global trends in diabetes complications: a review of current evidence

            In recent decades, large increases in diabetes prevalence have been demonstrated in virtually all regions of the world. The increase in the number of people with diabetes or with a longer duration of diabetes is likely to alter the disease profile in many populations around the globe, particularly due to a higher incidence of diabetes-specific complications, such as kidney failure and peripheral arterial disease. The epidemiology of other conditions frequently associated with diabetes, including infections and cardiovascular disease, may also change, with direct effects on quality of life, demands on health services and economic costs. The current understanding of the international burden of and variation in diabetes-related complications is poor. The available data suggest that rates of myocardial infarction, stroke and amputation are decreasing among people with diabetes, in parallel with declining mortality. However, these data predominantly come from studies in only a few high-income countries. Trends in other complications of diabetes, such as end-stage renal disease, retinopathy and cancer, are less well explored. In this review, we synthesise data from population-based studies on trends in diabetes complications, with the objectives of: (1) characterising recent and long-term trends in diabetes-related complications; (2) describing regional variation in the excess risk of complications, where possible; and (3) identifying and prioritising gaps for future surveillance and study.
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              National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants.

              Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. In 2008, global age-standardised mean FPG was 5·50 mmol/L (95% uncertainty interval 5·37-5·63) for men and 5·42 mmol/L (5·29-5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8% (8·6-11·2) in men and 9·2% (8·0-10·5) in women in 2008, up from 8·3% (6·5-10·4) and 7·5% (5·8-9·6) in 1980. The number of people with diabetes increased from 153 (127-182) million in 1980, to 347 (314-382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73-6·49 for men; 6·08 mmol/L, 5·72-6·46 for women) and diabetes prevalence (15·5%, 11·6-20·1 for men; and 15·9%, 12·1-20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. Bill & Melinda Gates Foundation and WHO. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Anal Cell Pathol (Amst)
                Anal Cell Pathol (Amst)
                acp
                Analytical Cellular Pathology (Amsterdam)
                Hindawi
                2210-7177
                2210-7185
                2021
                4 June 2021
                : 2021
                Affiliations
                1Dean McGee Eye Institute, Oklahoma University Health Sciences Center, 608 Stanton L Young Blvd, Oklahoma City, OK 73104, USA
                2North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
                3Department of Pharmaceutical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
                4Department of Physiology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young, Oklahoma City, OK, USA
                5Harold Hamm Oklahoma Diabetes Center, 1000 N Lincoln Blvd, Oklahoma City, OK, USA
                6Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA
                Author notes

                Academic Editor: Viswanathan Pragasam

                Article
                10.1155/2021/9913210
                8203386
                34194958
                Copyright © 2021 Thi N. Lam et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: National Eye Institute
                Award ID: EY028949
                Categories
                Research Article

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