Journal of Diabetes Research The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity Mon, 25 Jul 2016 08:10:51 +0000 Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity. Perla-Monserrat Madrigal-Ruíz, Rosa-Elena Navarro-Hernández, Sandra-Luz Ruíz-Quezada, Fernanda-Isadora Corona-Meraz, Mónica Vázquez-Del Mercado, Eduardo Gómez-Bañuelos, Jorge Castro-Albarran, Flavio Sandoval-García, Luis-Javier Flores-Alvarado, and Beatriz-Teresita Martín-Marquez Copyright © 2016 Perla-Monserrat Madrigal-Ruíz et al. All rights reserved. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease Wed, 20 Jul 2016 11:29:56 +0000 The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60–89 mL/min/1.73 m2), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is <30 mg/day. Albuminuria represents the excretion of >300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health. Alejandra Guillermina Miranda-Díaz, Leonardo Pazarín-Villaseñor, Francisco Gerardo Yanowsky-Escatell, and Jorge Andrade-Sierra Copyright © 2016 Alejandra Guillermina Miranda-Díaz et al. All rights reserved. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review Tue, 19 Jul 2016 12:15:05 +0000 A growing body of evidence has shown the intimate relationship between metabolomic profiles and insulin resistance (IR) in obese adults, while little is known about childhood obesity. In this review, we searched available papers addressing metabolomic profiles and IR in obese children from inception to February 2016 on MEDLINE, Web of Science, the Cochrane Library,, and EMASE. HOMA-IR was applied as surrogate markers of IR and related metabolic disorders at both baseline and follow-up. To minimize selection bias, two investigators independently completed this work. After critical selection, 10 studies (including 2,673 participants) were eligible and evaluated by using QUADOMICS for quality assessment. Six of the 10 studies were classified as “high quality.” Then we generated all the metabolites identified in each study and found amino acid metabolism and lipid metabolism were the main affected metabolic pathways in obese children. Among identified metabolites, branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), and acylcarnitines were reported to be associated with IR as biomarkers most frequently. Additionally, BCAAs and tyrosine seemed to be relevant to future metabolic risk in the long-term follow-up cohorts, emphasizing the importance of early diagnosis and prevention strategy. Because of limited scale and design heterogeneity of existing studies, future studies might focus on validating above findings in more large-scale and longitudinal studies with elaborate design. Xue Zhao, Xiaokun Gang, Yujia Liu, Chenglin Sun, Qing Han, and Guixia Wang Copyright © 2016 Xue Zhao et al. All rights reserved. Association between Serum Albumin Concentration and Ketosis Risk in Hospitalized Individuals with Type 2 Diabetes Mellitus Mon, 18 Jul 2016 12:12:11 +0000 Objective. This study examined the association between serum albumin concentration and ketosis risk in hospitalized individuals with type 2 diabetes mellitus (T2DM). Methods. A retrospective cross-sectional study was conducted at a medical center in Taiwan. Inclusion criteria were endocrinology ward inpatients exceeding 21 years of age, with preexisting diagnosis of T2DM, and blood glucose above 13.9 millimoles per liter (mmol/L) at admission. Individuals without measurement of serum albumin, urine ketone, or hemoglobin A1C, or harboring active infection, myocardial infarction, cerebrovascular event, cirrhosis, malignancy, or overt proteinuria were excluded. Using serum albumin concentration below 3.0 grams per deciliter to define hypoalbuminemia, 151 hypoalbuminemic cases and 104 normoalbuminemic controls were enrolled. The presence of ketones in urine established ketosis. Results. The prevalence of ketonuria was 48% in hypoalbuminemic subjects compared to 30% in normoalbuminemic controls (odds ratio (OR): 2.15; 95% confidence interval (CI): 1.26–3.57; ). Moreover, among the 156 subjects with serum beta-hydroxybutyrate measurement in addition to urine ketone, 33% of the hypoalbuminemic individuals had ketonemia exceeding 3 mmol/L compared to 19% of those with normoalbuminemia (OR: 2.12, 95% CI: 0.99–4.48, ). Conclusions. Serum albumin concentration is inversely associated with ketosis risk in hospitalized individuals with T2DM. Po-Chung Cheng, Shang-Ren Hsu, and Yun-Chung Cheng Copyright © 2016 Po-Chung Cheng et al. All rights reserved. Small Mouse Islets Are Deficient in Glucagon-Producing Alpha Cells but Rich in Somatostatin-Secreting Delta Cells Mon, 18 Jul 2016 09:33:50 +0000 Small and big mouse islets were compared with special reference to their content of glucagon-producing α-cells and somatostatin-producing δ-cells. Areas stained for glucagon and somatostatin were measured in the largest cross section of small (diameter < 60 μm) and big (diameter > 100 μm) islets. Comparison of the areas indicated proportionally more δ- than α-cells in the small islets. After isolation with collagenase these islets were practically devoid of α-cells. We evaluated the functional importance of the islet size by measuring the Ca2+ signal for insulin release. A majority of the small islets responded to the hyperpolarization action of somatostatin with periodic decrease of cytoplasmic Ca2+ when glucose was elevated after tolbutamide blockade of the channels. Joey Lau, Eva Grapengiesser, and Bo Hellman Copyright © 2016 Joey Lau et al. All rights reserved. Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model Mon, 18 Jul 2016 07:33:29 +0000 Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed. A. Schaschkow, C. Mura, S. Dal, A. Langlois, E. Seyfritz, C. Sookhareea, W. Bietiger, C. Peronet, N. Jeandidier, M. Pinget, S. Sigrist, and E. Maillard Copyright © 2016 A. Schaschkow et al. All rights reserved. The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective Study Sun, 17 Jul 2016 14:15:24 +0000 Background. The aim of this study was to validate the impact of type 2 diabetes (T2D) on the platelet reactivity in patients with acute ST elevation myocardial infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers. Methods. A pilot prospective study was performed. Totally 67 patients were enrolled. 21 patients had T2D. Among all study population, 33 patients received clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor blocker therapy had been tested in two time intervals using light transmission aggregometry with specific inducer and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant differences in platelet aggregability among T2D and nondiabetic (ND) group. The platelet reactivity index of VASP-P did not differ significantly between T2D and ND group (% versus % and % versus % in second testing). The number of ADP receptor blocker nonresponders did not differ significantly between T2D and ND patients. The time interval from ADP receptor blocker loading dosing to the blood sampling was similar in T2D and ND patients in both examinations. Conclusion. This prospective study did not confirm the higher platelet reactivity and higher prevalence of ADP receptor blocker nonresponders in T2D acute STEMI patients. Matej Samoš, Marián Fedor, František Kovář, Peter Galajda, Tomáš Bolek, Lucia Stančiaková, Jana Fedorová, Ján Staško, Peter Kubisz, and Marián Mokáň Copyright © 2016 Matej Samoš et al. All rights reserved. Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands Wed, 13 Jul 2016 06:17:08 +0000 Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions. M. Knaś, M. Maciejczyk, I. Daniszewska, A. Klimiuk, J. Matczuk, U. Kołodziej, D. Waszkiel, J. R. Ładny, M. Żendzian-Piotrowska, and A. Zalewska Copyright © 2016 M. Knaś et al. All rights reserved. Smoking Cessation Carries a Short-Term Rising Risk for Newly Diagnosed Diabetes Mellitus Independently of Weight Gain: A 6-Year Retrospective Cohort Study Tue, 12 Jul 2016 11:58:36 +0000 Background. The effects of smoking on human metabolism are complex. Although smoking increases risk for diabetes mellitus, smoking cessation was also reported to be associated with weight gain and incident diabetes mellitus. We therefore conducted this study to clarify the association between smoking status and newly diagnosed diabetes mellitus. Methods. An analysis was done using the data of a mass health examination performed annually in an industrial park from 2007 to 2013. The association between smoking status and newly diagnosed diabetes mellitus was analyzed with adjustment for weight gain and other potential confounders. Results. Compared with never-smokers, not only current smokers but also ex-smokers in their first two years of abstinence had higher odds ratios (ORs) for newly diagnosed diabetes mellitus (never-smokers 3.6%, OR as 1; current smokers 5.5%, OR = 1.499, 95% CI = 1.147–1.960, and ; ex-smokers in their first year of abstinence 7.5%, OR = 1.829, 95% CI = 0.906–3.694, and ; and ex-smokers in their second year of abstinence 9.0%, OR = 2.020, 95% CI = 1.031–3.955, and ). Conclusion. Smoking cessation generally decreased risk for newly diagnosed diabetes mellitus. However, increased odds were seen within the first 2 years of abstinence independently of weight gain. Yi-Ting Sung, Cheng-Ting Hsiao, I-Jen Chang, Yu-Chih Lin, and Chen-Yu Yueh Copyright © 2016 Yi-Ting Sung et al. All rights reserved. Does Hsp60 Provide a Link between Mitochondrial Stress and Inflammation in Diabetes Mellitus? Tue, 12 Jul 2016 07:43:34 +0000 The focus of this review is to summarise the known relationships between the expression of heat shock protein 60 (Hsp60) and its association with the pathogenesis of Type 1 and Type 2 diabetes mellitus. Hsp60 is a mitochondrial stress protein that is induced by mitochondrial impairment. It is known to be secreted from a number of cell types and circulating levels have been documented in both Types 1 and 2 diabetes mellitus patients. The biological significance of extracellular Hsp60, however, remains to be established. We will examine the links between Hsp60 and cellular anti- and proinflammatory processes and specifically address how Hsp60 appears to affect immune inflammation by at least two different mechanisms: as a ligand for innate immune receptors and as an antigen recognised by adaptive immune receptors. We will also look at the role of Hsp60 during immune cell activation in atherosclerosis, a significant risk factor during the pathogenesis of diabetes mellitus. Joshua Juwono and Ryan D. Martinus Copyright © 2016 Joshua Juwono and Ryan D. Martinus. All rights reserved. Topical Administration of Pirfenidone Increases Healing of Chronic Diabetic Foot Ulcers: A Randomized Crossover Study Sun, 10 Jul 2016 14:36:00 +0000 Only 30 percent of chronic diabetic foot ulcers heal after 20 weeks of standard treatment. Pirfenidone is a drug with biological, anti-inflammatory, and antifibrotic effects. The aim of this study was to evaluate the effect of topical pirfenidone added to conventional treatment in noninfected chronic diabetic foot ulcers. This was a randomized crossover study. Group 1 received topical pirfenidone plus conventional treatment for 8 weeks; after this period, they were switched to receive conventional treatment only for 8 more weeks. In group 2, the order of the treatments was the opposite. The end points were complete ulcer healing and size reduction. Final data were obtained from 35 ulcers in 24 patients. Fifty-two percent of ulcers treated with pirfenidone healed before 8 weeks versus 14.3% treated with conventional treatment only (). Between 8 and 16 weeks, 30.8% ulcers that received pirfenidone healed versus 0% with conventional treatment (). By week 8, the reduction in ulcer size was 100% [73–100] with pirfenidone versus 57.5% with conventional treatment [28.9–74] (). By week 16, the reduction was 93% [42.7–100] with pirfenidone and 21.8% [8–77.5] with conventional treatment (). The addition of topical pirfenidone to conventional treatment significantly improves the healing of chronic diabetic noninfected foot ulcers. Marcela Janka-Zires, Paloma Almeda-Valdes, Ana Cecilia Uribe-Wiechers, Sonia Citlali Juárez-Comboni, Joel López-Gutiérrez, Jarod Jazek Escobar-Jiménez, and Francisco J. Gómez-Pérez Copyright © 2016 Marcela Janka-Zires et al. All rights reserved. Evaluating the Effect of Knowledge, Attitude, and Practice on Self-Management in Type 2 Diabetic Patients on Dialysis Sun, 10 Jul 2016 14:27:40 +0000 Background. Type 2 diabetes is an increasingly common condition with several preventable microvascular complications such as kidney damage. Nephropathy is expensive to manage, especially as hospital dialysis treatment. Improving patients’ knowledge, attitude, and practice (KAP) toward their condition can achieve better control, delay complications, and improve their quality of life. This study evaluated the KAP and self-care behaviors of diabetic patients on dialysis and variables that affect it. Methods. This cross-sectional study was conducted at Shahid Beheshti academic hospitals of Tehran, Iran. Face-to-face interviews were held to fill five validated questionnaires: three evaluating KAP, one evaluating self-management, and one evaluating quality of life. Result. 117 diabetic patients on hemodialysis (42 females) with mean (SD) age of years were enrolled in the survey. The scores for patient’s KAP, self-care, and quality of life were , , , , and , respectively. There was significant negative correlation between patients’ knowledge and attitude with their glycosylated hemoglobin level and their fasting blood sugar. There was significant correlation between patients’ knowledge and practice with their self-care activities. Conclusion. The present study suggests that patients’ KAP scores have a practical effect upon self-care behavior. This highlights the needs for effective diabetes education programs in developing countries like Iran. Shima Ghannadi, Atieh Amouzegar, Parisa Amiri, Ronak Karbalaeifar, Zhale Tahmasebinejad, and Sara Kazempour-Ardebili Copyright © 2016 Shima Ghannadi et al. All rights reserved. Xerostomia, Hyposalivation, and Salivary Flow in Diabetes Patients Sun, 10 Jul 2016 07:09:33 +0000 The presence of xerostomia and hyposalivation is frequent among diabetes mellitus (DM) patients. It is not clear if the presence of xerostomia and hyposalivation is greater in DM than non-DM patients. The aims of this systematic review are (1) to compare the prevalence rates of xerostomia, (2) to evaluate the salivary flow rate, and (3) to compare the prevalence rates of hyposalivation in DM versus non-DM population. This systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in biomedical databases from 1970 until January 18th, 2016. All studies showed higher prevalence of xerostomia in DM patients in relation to non-DM population, 12.5%–53.5% versus 0–30%. Studies that analyzed the quantity of saliva in DM population in relation to non-DM patients reported higher flow rates in non-DM than in DM patients. The variation flow rate among different studies in each group (DM/CG) is very large. Only one existing study showed higher hyposalivation prevalence in DM than non-DM patients (45% versus 2.5%). In addition, quality assessment showed the low quality of the existing studies. We recommend new studies that use more precise and current definitions concerning the determination and diagnosis of DM patients and salivary flow collection. Rosa María López-Pintor, Elisabeth Casañas, José González-Serrano, Julia Serrano, Lucía Ramírez, Lorenzo de Arriba, and Gonzalo Hernández Copyright © 2016 Rosa María López-Pintor et al. All rights reserved. Insulin Resistance and Obesity Affect Lipid Profile in the Salivary Glands Tue, 05 Jul 2016 09:40:16 +0000 In today’s world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus. Jan Matczuk, Anna Zalewska, Bartłomiej Łukaszuk, Małgorzata Knaś, Mateusz Maciejczyk, Marta Garbowska, Dominika M. Ziembicka, Danuta Waszkiel, Adrian Chabowski, Małgorzata Żendzian-Piotrowska, and Krzysztof Kurek Copyright © 2016 Jan Matczuk et al. All rights reserved. Analysis of Inflammatory Mediators in Prediabetes and Newly Diagnosed Type 2 Diabetes Patients Tue, 05 Jul 2016 07:02:48 +0000 This study evaluated the inflammatory markers in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Inflammatory markers levels were analyzed using one-way analysis of covariance and the association with prediabetes or T2DM risks was examined by logistic regression models. Our data showed increased levels of hypersensitivity C-reactive protein (hs-CRP), interleukin (IL-4), IL-10, and tryptase in prediabetes subjects and hs-CRP, immunoglobulin E (IgE), IL-4, and IL-10 in T2DM subjects. We concluded that Hs-CRP, IgE, IL-4, IL-10, and tryptase were positively associated with prediabetes or T2DM. Further large prospective studies are warranted to assess a temporal relation between inflammatory biomarkers and incidence of prediabetes or T2DM and its associated chronic diseases. Zhen Wang, Xu-Hui Shen, Wen-Ming Feng, Guo-fen Ye, Wei Qiu, and Bo Li Copyright © 2016 Zhen Wang et al. All rights reserved. Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy Thu, 30 Jun 2016 13:35:13 +0000 Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling. Ning Yan, Li Wen, Rui Peng, Hongmei Li, Handeng Liu, Huimin Peng, Yan Sun, Tianhui Wu, Lei Chen, Qingrui Duan, Yixuan Sun, Qin Zhou, Lijiang Wei, and Zheng Zhang Copyright © 2016 Ning Yan et al. All rights reserved. Development and Evaluation of a Computer-Based, Self-Management Tool for People Recently Diagnosed with Type 2 Diabetes Thu, 30 Jun 2016 12:34:22 +0000 Aim. The purpose of this study was to develop and evaluate a computer-based, dietary, and physical activity self-management program for people recently diagnosed with type 2 diabetes. Methods. The computer-based program was developed in conjunction with the target group and evaluated in a 12-week randomised controlled trial (RCT). Participants were randomised to the intervention (computer-program) or control group (usual care). Primary outcomes were diabetes knowledge and goal setting (ADKnowl questionnaire, Diabetes Obstacles Questionnaire (DOQ)) measured at baseline and week 12. User feedback on the program was obtained via a questionnaire and focus groups. Results. Seventy participants completed the 12-week RCT (32 intervention, 38 control, mean age 59 (SD) years). After completion there was a significant between-group difference in the “knowledge and beliefs scale” of the DOQ. Two-thirds of the intervention group rated the program as either good or very good, 92% would recommend the program to others, and 96% agreed that the information within the program was clear and easy to understand. Conclusions. The computer-program resulted in a small but statistically significant improvement in diet-related knowledge and user satisfaction was high. With some further development, this computer-based educational tool may be a useful adjunct to diabetes self-management. This trial is registered with NCT number NCT00877851. Alison O. Booth, Carole Lowis, Steven J. Hunter, Moira Dean, Chris R. Cardwell, and Michelle C. McKinley Copyright © 2016 Alison O. Booth et al. All rights reserved. Prevalence and Risk Factors for Diabetic Lower Limb Amputation: A Clinic-Based Case Control Study Wed, 29 Jun 2016 10:51:34 +0000 Objective. The aim of the study was to evaluate the prevalence of and risk factors for lower limb amputation in a specialist foot clinic-based setting. Methods. A retrospective quantitative study was conducted, using clinical and biochemical profiles of diabetic foot patients attending the High Risk Foot Clinic at The Townsville Hospital, Australia, between January 1, 2011, and December 31, 2013. Results. The total study sample included 129 subjects, comprising 81 males and 48 females with M : F ratio of 1.7 : 1. Twenty-three subjects were Indigenous Australians, representing 17.8% of the study population. The average age of the cohort was 63.4 years ± 14.1 years [CI 90.98–65.89]. Lower limb amputation was identified as a common and significant outcome (), occurring in 34.1%, more commonly amongst the Indigenous Australians (56.5% versus 29.2%; , OR 0.94). Risk factors most closely associated with amputation included diabetic retinopathy (, OR 4.4), coronary artery bypass graft (CABG) surgery (, OR 4.1), Charcot’s arthropathy (, OR 2.9), and Indigenous ethnicity (, OR 3.4). Although average serum creatinine, corrected calcium, and glycosylated haemoglobin A1c (Hba1c) levels were higher amongst amputees they were statistically insignificant. Conclusions. Lower limb amputation is a common outcome and linked to ethnicity and neurovascular diabetic complications amongst subjects with diabetic foot ulcer. Further research is needed to identify why risk of lower limb amputation seems to differ according to ethnicity. Beverly T. Rodrigues, Venkat N. Vangaveti, and Usman H. Malabu Copyright © 2016 Beverly T. Rodrigues et al. All rights reserved. Antidiabetic Medicinal Plants Used by the Basotho Tribe of Eastern Free State: A Review Wed, 29 Jun 2016 10:48:37 +0000 Diabetes mellitus (DM) belongs to the group of five leading important diseases causing death globally and remains a major health problem in Africa. A number of factors such as poverty, poor eating habit, and hormonal imbalance are responsible for the occurrence of the disease. It poses a major health challenge in Africa continent today and the prevalence continues to increase at an alarming rate. Various treatment options particularly the usage of herbs have been effective against diabetes because they have no adverse effects. Interestingly, South Africa, especially the Basotho tribe, is blessed with numerous medicinal plants whose usage in the treatment of DM has been effective since the conventional drugs are expensive and often unaffordable. The present study attempted to update the various scientific evidence on the twenty-three (23) plants originating from different parts of the world but widely used by the Sotho people in the management of DM. Asteraceae topped the list of sixteen (16) plant families and remained the most investigated according to this review. Although limited information was obtained on the antidiabetic activities of these plants, it is however anticipated that government parastatals and scientific communities will pay more attention to these plants in future research. Fatai Oladunni Balogun, Natu Thomas Tshabalala, and Anofi Omotayo Tom Ashafa Copyright © 2016 Fatai Oladunni Balogun et al. All rights reserved. Corneal Endothelial Morphology in Children with Type 1 Diabetes Sun, 26 Jun 2016 08:23:29 +0000 Aim. To investigate corneal endothelial cell morphological in children with type 1 diabetes and to determine the systemic and local factors that contribute to these changes. Methods. One hundred sixty eyes of 80 children with type 1 diabetes and 80 eyes of 40 normal children as a control during the period from July 2015 to February 2016 underwent full clinical and ophthalmologic examination. We measured the central corneal thickness (CCT), endothelial cell density (ECD), ploymegathism, and pleomorphism using a noncontact specular microscope. Results. The mean age of the diabetic children was years. The mean duration of type 1 diabetes was years. The mean CCT was significantly higher: microns (right eye), in the diabetic group compared to the control group. The mean ECD in patients with type 1 diabetes was cells/mm2 (right eye), and it was significantly lower than in the control group. Furthermore, pleomorphism was significantly lower % (right eye), in the diabetic group compared to the control group. The mean polymegathism was significantly higher % (right eye), in the diabetic group compared to the control group. All of these changes are significantly correlated only with the duration of diabetes. Conclusions. Diabetic children have thicker corneas, lower ECD, an increased polymegathism, and a decreased pleomorphism. The duration of diabetes is the factor that affects all of these changes. To what extent these changes affect visional function on long term needs to be investigated in further studies. Mohamed Anbar, Hatem Ammar, and Ramadan A. Mahmoud Copyright © 2016 Mohamed Anbar et al. All rights reserved. Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance Wed, 22 Jun 2016 14:32:54 +0000 Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients ( years, 52.0% males) with DCM and thirty-one normal healthy controls ( years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E′, A′, and E′/A′) were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) () and no significant difference was in mass at end diastole (). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E′ (all ). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM. Yongning Shang, Xiaochun Zhang, Liu Chen, Weiling Leng, Xiaotian Lei, Qi Yang, Ziwen Liang, and Jian Wang Copyright © 2016 Yongning Shang et al. All rights reserved. Role of Tissue and Systemic Hypoxia in Obesity and Type 2 Diabetes Tue, 21 Jun 2016 13:45:17 +0000 Lei Xi, Chin-Moi Chow, and Xingxing Kong Copyright © 2016 Lei Xi et al. All rights reserved. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy Thu, 16 Jun 2016 14:20:35 +0000 Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN. Cristina Gluhovschi, Gheorghe Gluhovschi, Ligia Petrica, Romulus Timar, Silvia Velciov, Ioana Ionita, Adriana Kaycsa, and Bogdan Timar Copyright © 2016 Cristina Gluhovschi et al. All rights reserved. Activation of GPR119 Stimulates Human β-Cell Replication and Neogenesis in Humanized Mice with Functional Human Islets Thu, 16 Jun 2016 10:20:45 +0000 Using humanized mice with functional human islets, we investigated whether activating GPR119 by PSN632408, a small molecular agonist, can stimulate human β-cell regeneration in vivo. Human islets were transplanted under the left kidney capsule of immunodeficient mice with streptozotocin- (STZ-) induced diabetes. The recipient mice were treated with PSN632408 or vehicle and BrdU daily. Human islet graft function in the mice was evaluated by nonfasting glucose levels, oral glucose tolerance, and removal of the grafts. Immunostaining for insulin, glucagon, and BrdU or Ki67 was performed in islet grafts to evaluate α- and β-cell replication. Insulin and CK19 immunostaining was performed to evaluate β-cell neogenesis. Four weeks after human islet transplantation, 71% of PSN632408-treated mice achieved normoglycaemia compared with 24% of vehicle-treated mice. Also, oral glucose tolerance was significantly improved in the PSN632408-treated mice. PSN632408 treatment significantly increased both human α- and β-cell areas in islet grafts and stimulated α- and β-cell replication. In addition, β-cell neogenesis was induced from pancreatic duct cells in the islet grafts. Our results demonstrated that activation of GPR119 increases β-cell mass by stimulating human β-cell replication and neogenesis. Therefore, GPR119 activators may qualify as therapeutic agents to increase human β-cell mass in patients with diabetes. Ansarullah, Colette Free, Jenica Christopherson, Quanhai Chen, Jie Gao, Chengyang Liu, Ali Naji, Alex Rabinovitch, and Zhiguang Guo Copyright © 2016 Ansarullah et al. All rights reserved. Screening of Undiagnosed Hypothyroidism in Elderly Persons with Diabetes according to Age-Specific Reference Intervals for Serum Thyroid Stimulating Hormone and the Impact of Antidiabetes Drugs Wed, 15 Jun 2016 11:57:27 +0000 Background. Studies have suggested that hypothyroidism is more frequent in the elderly with diabetes mellitus. However, an adaptation of TSH levels to age should be considered in this assessment. Some antidiabetes drugs reportedly interfere with TSH levels. The objectives of this study were to evaluate the prevalence of undiagnosed hypothyroidism in patients with diabetes and the influence of antidiabetes drugs. Material and Methods. 1160 subjects, 60 years and older (751 with diabetes), were studied; results were compared according to diabetes treatment and with persons without diabetes. TSH, FT4, antithyroperoxidase, fasting glucose, and HbA1c were measured. Results and Discussion. 6.4% of patients with diabetes had hypothyroidism, a higher prevalence compared with persons without diabetes (5.1%), but lower than observed in many studies. The use of age-specific TSH reference interval (RI) could explain this difference. Patients taking metformin (MTF) had TSH (showed in medians) slightly lower (2.8 mU/L) than those not on MTF (3.3 mU/L), . MTF doses influenced TSH levels. Conclusions. The use of specific TSH RI could avoid the misdiagnosis of hypothyroidism in elderly with diabetes. Patients in use of MTF as single drug had lower TSH than those using other medications and persons without diabetes. Rosita Fontes, Patricia de Fatima dos Santos Teixeira, and Mario Vaisman Copyright © 2016 Rosita Fontes et al. All rights reserved. The Hospitalization Costs of Diabetes and Hypertension Complications in Zimbabwe: Estimations and Correlations Wed, 15 Jun 2016 06:38:17 +0000 Objective. Treating complications associated with diabetes and hypertension imposes significant costs on health care systems. This study estimated the hospitalization costs for inpatients in a public hospital in Zimbabwe. Methods. The study was retrospective and utilized secondary data from medical records. Total hospitalization costs were estimated using generalized linear models. Results. The median cost and interquartile range (IQR) for patients with diabetes, $994 (385–1553) mean $1319 (95% CI: 981–1657), was higher than patients with hypertension, $759 (494–1147) mean $914 (95% CI: 825–1003). Female patients aged below 65 years with diabetes had the highest estimated mean costs ($1467 (95% CI: 1177–1828)). Wound care had the highest estimated mean cost of all procedures, $2884 (95% CI: 2004–4149) for patients with diabetes and $2239 (95% CI: 1589–3156) for patients with hypertension. Age below 65 years, medical procedures (amputation, wound care, dialysis, and physiotherapy), the presence of two or more comorbidities, and being prescribed two or more drugs were associated with significantly higher hospitalization costs. Conclusion. Our estimated costs could be used to evaluate and improve current inpatient treatment and management of patients with diabetes and hypertension and determine the most cost-effective interventions to prevent complications and comorbidities. Mutsa P. Mutowo, Paula K. Lorgelly, Michael Laxy, Andre M. N. Renzaho, John C. Mangwiro, and Alice J. Owen Copyright © 2016 Mutsa P. Mutowo et al. All rights reserved. The Relation between Serum Uric Acid and HbA1c Is Dependent upon Hyperinsulinemia in Patients with Newly Diagnosed Type 2 Diabetes Mellitus Tue, 14 Jun 2016 07:42:45 +0000 Objective. The aim of our study was to explore the dependent condition of the relationship between uric acid and blood glucose in type 2 diabetes. Research Design and Methods. We measured the HbA1c, serum uric acid, creatinine, lipids profiles, and so forth of 605 newly diagnosed type 2 diabetes patients, and oral glucose tolerance tests (OGTTs) were performed on each patient. The population was divided into high and low insulin groups. Multiple linear regression analyses were conducted to assess the relationship between uric acid and HbA1c. Results. Serum uric acid and HbA1c levels were low in newly diagnosed type 2 diabetes patients. However, we found no significant relationship between uric acid and HbA1c by regression analysis after adjusting total insulin. The concentration of uric acid was inversely correlated with HbA1c in the high insulin group, regardless of patient sex. However, no associations were found in low insulin group. Conclusions. The negative correlation between uric acid and HbA1c is conditional in newly diagnosed type 2 diabetes patients and is related to hyperinsulinemia. Therefore, uric acid is likely only useful as a biomarker of blood glucose in patients exhibiting hyperinsulinemia. Yuliang Cui, Hemei Bu, Xianghua Ma, Sha Zhao, Xiaona Li, and Shan Lu Copyright © 2016 Yuliang Cui et al. All rights reserved. Interaction between Mean Arterial Pressure and HbA1c in Prediction of Cardiovascular Disease Hospitalisation: A Population-Based Case-Control Study Mon, 13 Jun 2016 10:42:02 +0000 Objective. To explore the relationship between mean arterial pressure (MAP), HbA1c, and cardiovascular (CV) hospitalisation risk in type 2 diabetes. Design. Population-based case-control study. Settings. Primary and secondary care level in Cambridgeshire, United Kingdom. Participants. 588 patients with type 2 diabetes from 18 English general practices recording a CV hospitalisation in 2009–2011 were included. Risk-set sampling was used to select 2920 gender, age, and practice matched control type 2 diabetes patients. Main Outcome Measure. Conditional logistic regression was used to explore further dose-response relationships between MAP, HbA1c, and CV hospitalisation risk. Results. The relationship between MAP and CV hospitalisation was nonlinear ( for linearity test). The MAP associated with the lowest CV hospitalisation risk was 97 (95% CI: 93–101) mmHg. An interaction between MAP and HbA1c for increased risk of cardiovascular hospitalisation was observed among those with HbA1c < 7% (53 mmol/mol) and MAP < 97 mmHg. Conclusions. In type 2 diabetes, MAP is a good predictor of CV hospitalisation risk. CV hospitalisation is lowest with a MAP between 93 and 101 mmHg. CV hospitalisation was particularly high among those with both a low MAP and a lower HbA1c. Dahai Yu, Zhanzheng Zhao, and David Simmons Copyright © 2016 Dahai Yu et al. All rights reserved. Increasing GLP-1 Circulating Levels by Bariatric Surgery or by GLP-1 Receptor Agonists Therapy: Why Are the Clinical Consequences so Different? Sun, 12 Jun 2016 07:32:45 +0000 The “incretin effect” is used to describe the observation that more insulin is secreted after the oral administration of glucose compared to that after the intravenous administration of the same amount of glucose. During the absorption of meals, the gut is thought to regulate insulin secretion by secreting a specific factor that targets pancreatic beta cells. Additional research confirmed this hypothesis with the discovery of two hormones called incretins: gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1). During meals, specific cells in the gut (L and K enteroendocrine cells) secrete incretins, causing an increase in the blood concentrations of, respectively, GLP-1 and GIP. Bariatric surgery is now proposed during the therapeutic management of type 2 diabetes in obese or overweight populations. It has been hypothesized that restoration of endogenous GLP-1 secretion after the surgery may contribute to the postsurgical resolution of diabetes. In 2005, the commercialization of GLP-1 receptor agonists gave the possibility to test this hypothesis. A few years later, it is now accepted that GLP-1 receptor agonists and bariatric surgery differently improve type 2 diabetes. These differences between endogenous and exogenous GLP-1 on glucose homeostasis emphasized the dual properties of GLP-1 as a peptide hormone and as a neurotransmitter. Chloé Amouyal and Fabrizio Andreelli Copyright © 2016 Chloé Amouyal and Fabrizio Andreelli. All rights reserved. Sex-Specific Association between Serum Uric Acid and Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Patients Sun, 12 Jun 2016 06:55:11 +0000 Across-sectional study was performed in 541 type 2 diabetic patients to determine the relationship between serum uric acid (SUA) and NAFLD in type 2 diabetic patients. Clinical parameters including SUA were determined and NAFLD was diagnosed by ultrasonography. SUA was significantly higher in type 2 diabetic subjects with NAFLD than in those without NAFLD in men, but not in women. Furthermore, the prevalence rate of NAFLD increased progressively across the sex-specific SUA tertiles only in men (37.9%, 58.6%, and 72.6%, resp., for trend < 0.001). After adjusting for confounding factors, the odd ratios (95% CI) for NAFLD were 1 (reference), 2.93 (95%CI 1.25–6.88), and 3.93 (95% CI 1.55–9.98), respectively, across the tertiles of SUA in men. Contrastingly, SUA levels in women were not independently associated with the risk of NAFLD. Our data suggests that SUA is specifically associated with NAFLD in male type 2 diabetic subjects, independent of insulin resistance and other metabolic factors. Nengguang Fan, Lijuan Zhang, Zhenhua Xia, Liang Peng, Yufan Wang, and Yongde Peng Copyright © 2016 Nengguang Fan et al. All rights reserved.