Journal of Diabetes Research The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. The Role of Insulin Receptor Isoforms in Diabetes and Its Metabolic and Vascular Complications Thu, 19 Oct 2017 00:00:00 +0000 The insulin receptor (IR) presents by alternative splicing two isoforms: IRA and IRB. The differential physiological and pathological role of both isoforms is not completely known, and it is determinant the different binding affinity for insulin-like growth factor. IRB is more abundant in adult tissues and it exerts mainly the metabolic actions of insulin, whereas IRA is mainly expressed in fetal and prenatal period and exerts mitogenic actions. However, the change in the expression profile of both IR isoforms and its dysregulation are associated with the development of different pathologies, such as cancer, insulin resistance, diabetes, obesity, and atherosclerosis. In some of them, there is a significant increase of IRA/IRB ratio conferring a proliferative and migratory advantage to different cell types and favouring IGF-II actions with a sustained detriment in the metabolic effects of insulin. This review discussed specifically the role of IR isoforms as well as IGF-IR in diabetes and its associated complications as obesity and atherosclerosis. Future research with new IR modulators might be considered as possible targets to improve the treatment of diabetes and its associated complications. O. Escribano, N. Beneit, C. Rubio-Longás, A. R. López-Pastor, and A. Gómez-Hernández Copyright © 2017 O. Escribano et al. All rights reserved. Dynamics of Insulin Secretion from EndoC-βH1 β-Cell Pseudoislets in Response to Glucose and Other Nutrient and Nonnutrient Secretagogues Thu, 19 Oct 2017 00:00:00 +0000 The dynamics of insulin secretion were characterized in response to a variety of physiological and pharmacological stimulators and other compounds in perifused pseudoislets generated from cells of the EndoC-βH1 β-cell line. Perifusion of EndoC-βH1 pseudoislets with the physiological stimulus glucose (16.7 mM) induced sustained insulin secretion, which was inhibited by mannoheptulose. The adenylate cyclase activators IBMX and forskolin strongly potentiated this secretion. Glibenclamide, a Kir 6.2 potassium channel blocker, and Bay K 8644, an opener of the voltage-sensitive Ca2+ channel, also potentiated glucose-induced insulin secretion. The dynamics of insulin secretion from EndoC-βH1 pseudoislets were characterized by an insulin secretory response to glucose starting within 1-2 min and passing over without interruption into a sustained phase of insulin release for the whole stimulation period. This lack of a transient decline between the first and the second phases of insulin release is an indication for a quick supply of insulin secretory granules from the reserve pool to the docking sites below the plasma membrane. Thereby, new secretory granules are directly made available for sustained exocytosis of insulin in EndoC-βH1 β-cells. The study shows that EndoC-βH1 β-cell pseudoislets are well suited for kinetic analyses of insulin secretion. Hiroki Teraoku and Sigurd Lenzen Copyright © 2017 Hiroki Teraoku and Sigurd Lenzen. All rights reserved. Antioxidative Effects of Natural Products on Diabetic Cardiomyopathy Wed, 18 Oct 2017 00:00:00 +0000 Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes and results in high mortality. It is therefore imperative to develop novel therapeutics for the prevention or inhibition of the progression of DCM. Oxidative stress is a key mechanism by which diabetes induces DCM. Hence, targeting of oxidative stress-related processes in DCM could be a promising therapeutic strategy. To date, a number of studies have shown beneficial effects of several natural products on the attenuation of DCM via an antioxidative mechanism of action. The aim of the present review is to provide a comprehensive and concise overview of the previously reported antioxidant natural products in the inhibition of DCM progression. Clinical trials of the antioxidative natural products in the management of DCM are included. In addition, discussion and perspectives are further provided in the present review. Bingdi Yan, Jin Ren, Qinghua Zhang, Rong Gao, Fenglian Zhao, Junduo Wu, and Junling Yang Copyright © 2017 Bingdi Yan et al. All rights reserved. High Fasting Plasma Glucose during Early Pregnancy: A Review about Early Gestational Diabetes Mellitus Wed, 18 Oct 2017 00:00:00 +0000 Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing. E. Cosson, L. Carbillon, and P. Valensi Copyright © 2017 E. Cosson et al. All rights reserved. Comment on “Prevalence and Risk Factors for Diabetic Lower Limb Amputation: A Clinic-Based Case Control Study” Tue, 17 Oct 2017 00:00:00 +0000 M. Bakhtiyari and M. A. Mansournia Copyright © 2017 M. Bakhtiyari and M. A. Mansournia. All rights reserved. SIRT1 Regulates Cognitive Performance and Ability of Learning and Memory in Diabetic and Nondiabetic Models Sun, 15 Oct 2017 00:00:00 +0000 Type 2 diabetes mellitus is a complex age-related metabolic disease. Cognitive dysfunction and learning and memory deficits are main characteristics of age-related metabolic diseases in the central nervous system. The underlying mechanisms contributing to cognitive decline are complex, especially cognitive dysfunction associated with type 2 diabetes mellitus. SIRT1, as one of the modulators in insulin resistance, is indispensable for learning and memory. In the present study, deacetylation, oxidative stress, mitochondrial dysfunction, inflammation, microRNA, and tau phosphorylation are considered in the context of mechanism and significance of SIRT1 in learning and memory in diabetic and nondiabetic murine models. In addition, future research directions in this field are discussed, including therapeutic potential of its activator, resveratrol, and application of other compounds in cognitive improvement. Our findings suggest that SIRT1 might be a potential therapeutic target for the treatment of cognitive impairment induced by type 2 diabetes mellitus. Yue Cao, Zi Yan, Tong Zhou, and Guixia Wang Copyright © 2017 Yue Cao et al. All rights reserved. Foot Complications in a Representative Australian Inpatient Population Sun, 15 Oct 2017 00:00:00 +0000 We investigated the prevalence and factors independently associated with foot complications in a representative inpatient population (adults admitted for any reason with and without diabetes). We analysed data from the Foot disease in inpatients study, a sample of 733 representative inpatients. Previous amputation, previous foot ulceration, peripheral arterial disease (PAD), peripheral neuropathy (PN), and foot deformity were the foot complications assessed. Sociodemographic, medical, and foot treatment history were collected. Overall, 46.0% had a foot complication with 23.9% having multiple; those with diabetes had higher prevalence of foot complications than those without diabetes (). Previous amputation (4.1%) was independently associated with previous foot ulceration, foot deformity, cerebrovascular accident, and past surgeon treatment (). Previous foot ulceration (9.8%) was associated with PN, PAD, past podiatry, and past nurse treatment (). PAD (21.0%) was associated with older age, males, indigenous people, cancer, PN, and past surgeon treatment (). PN (22.0%) was associated with older age, diabetes, mobility impairment, and PAD (). Foot deformity (22.4%) was associated with older age, mobility impairment, past podiatry treatment, and PN (). Nearly half of all inpatients had a foot complication. Those with foot complications were older, male, indigenous, had diabetes, cerebrovascular accident, mobility impairment, and other foot complications or past foot treatment. Peter A. Lazzarini, Sheree E. Hurn, Suzanne S. Kuys, Maarten C. Kamp, Vanessa Ng, Courtney Thomas, Scott Jen, Jude Wills, Ewan M. Kinnear, Michael C. d’Emden, and Lloyd F. Reed Copyright © 2017 Peter A. Lazzarini et al. All rights reserved. The Diabetic Foot Tue, 10 Oct 2017 00:00:00 +0000 I. Migdalis, L. Czupryniak, N. Lalic, R. D. Leslie, N. Papanas, and P. Valensi Copyright © 2017 I. Migdalis et al. All rights reserved. Treatment Gaps Found in the Management of Type 2 Diabetes at a Community Health Centre in Johannesburg, South Africa Tue, 10 Oct 2017 00:00:00 +0000 Aims. The management of cardiometabolic goals or “ABCs” (HbA1c, blood pressure (BP), and cholesterol) ultimately determines the morbidity and mortality outcomes in patients with type 2 diabetes mellitus (T2DM). We sought to determine if patients with T2DM attending an urbanized public sector community health centre (CHC) were having their ABCs measured, were treated with appropriate cardioprotective agents and finally, were achieving guideline-based targets. Methods and Results. A cross-sectional record review of 519 patients was conducted between May and August 2015. The mean age was 54 years (SD: ±11.5) and 54% () were females. Testing of ABCs occurred in 68.8% () for HbA1c, 95.4% () for BP, and 58.6% () for LDL-C. Achievement of ABC targets was as follows: 19.3% (HbA1c < 7%), 22.0% (BP < 140/80 mmHg), and 56.3% (LDL-C < 2.5 mmol/l). Conclusion. There were a significant number of patients who were not tested nor received adequate pharmacotherapy or achieved their ABC targets. This places these patients at an increased risk for the development of diabetes-related complications. Although the realities of resource constraints exist in South Africa’s public sector settings, a wider implementation of evidence-based guidelines must be instituted in order to ensure better patient outcomes. Yacob Pinchevsky, Neil Butkow, Tobias Chirwa, and Frederick Raal Copyright © 2017 Yacob Pinchevsky et al. All rights reserved. Blocking AGE-RAGE Signaling Improved Functional Disorders of Macrophages in Diabetic Wound Sun, 08 Oct 2017 00:00:00 +0000 Advanced glycosylation end products (AGEs) accumulate in diabetic wounds. Interactions between AGEs and their receptor (RAGE) leads to dermatologic problems in diabetes. Macrophage, which plays important roles in wound healing, highly expresses RAGE. Therefore, we investigated whether RAGE-expressing macrophages might be responsible for impaired wound healing on diabetes. We used anti-RAGE antibody applied topically on diabetic wounds. After confirming that wound healing was improved in anti-RAGE antibody group compared with normal mice, our results showed that macrophages appeared insufficient in the early stage and fading away slowly in the later proliferative phase compared with the control group, which was ameliorated in anti-RAGE antibody-applied wounds. Blocking AGE-RAGE signaling also increased neutrophils phagocytized by macrophages and promoted the phenotypic switch of macrophages from proinflammatory to prohealing activities. In vitro, phagocytosis of THP-1 (M0) and lipopolysaccharide- (LPS-) induced (M1) macrophages was impaired by treatment with AGEs, while IL-4- and IL-13-induced (M2) macrophages was not. Finally, AGEs increased the proinflammatory response of M1 macrophages, while inhibiting the polarization and anti-inflammatory functions of M2 macrophages. In conclusion, inhibition of AGE-RAGE signaling improved functional disorders of macrophages in the early inflammatory phase, which promoted the healing of wounds in diabetic mice. Qi Wang, Guanya Zhu, Xiaozan Cao, Jiaoyun Dong, Fei Song, and Yiwen Niu Copyright © 2017 Qi Wang et al. All rights reserved. Diagnostic Accuracy of Monofilament Tests for Detecting Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis Sun, 08 Oct 2017 00:00:00 +0000 Objective. To systematically evaluate the diagnostic accuracy of monofilament tests for detecting diabetic peripheral neuropathy. Methods. We searched EMBASE (OvidSP), MEDLINE (OvidSP), the Cochrane Library, and Web of Science to identify diagnostic accuracy trials of monofilament tests for detecting diabetic peripheral neuropathy. We used a hierarchical summary receiver operating characteristics (HSROC) model to conduct the meta-analysis of diagnostic accuracy of monofilament tests for detecting diabetic peripheral neuropathy. Results. A total of 19 comparative trials met the inclusion criteria and were part of the qualitative synthesis. Eight trials using nerve conduction studies as the reference standard were selected for the meta-analysis. The pooled sensitivity and specificity of monofilament tests for detecting diabetic peripheral neuropathy were 0.53 (95% confidence interval (CI) 0.32 to 0.74) and 0.88 (95% CI 0.78 to 0.94), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 4.56 (95% CI 2.93 to 7.10) and 0.53 (95% CI 0.35 to 0.81), respectively. Conclusions. Our review indicated that monofilament tests had limited sensitivity for screening diabetic peripheral neuropathy. The clinical use of the monofilament test in the evaluation of diabetic peripheral neuropathy cannot be encouraged based on currently available evidence. Fengyi Wang, Jiaqi Zhang, Jiadan Yu, Shaxin Liu, Rengang Zhang, Xichao Ma, Yonghong Yang, and Pu Wang Copyright © 2017 Fengyi Wang et al. All rights reserved. Micronutrient Intake in a Cohort of Italian Adults with Type 1 Diabetes: Adherence to Dietary Recommendations Wed, 04 Oct 2017 06:52:37 +0000 Micronutrients are of fundamental importance in maintaining health status. However, data on their dietary intake are few particularly in persons with diabetes. The aim of this study was to evaluate in adults with type 1 diabetes (T1DM) attending a tertiary-level diabetes center in Southern Italy the intake of micronutrients (both vitamins and minerals) and the adherence to recommendations. Seven-day food records of 60 T1DM patients were analyzed. Micronutrient intake was evaluated based on the Italian food composition tables and expressed as amount per 1000 kcal of energy intake to adjust for possible underreporting. Adherence to recommendations for vitamins A, B6, B12, and C and niacin was acceptable in both sexes (ranging from 77% to 100%). Half of the patients did not adhere to folate recommendation, even less to vitamin E, and no patient reached the recommended intake for vitamin D. As for minerals, adherence was low for potassium and selenium (0–23%); intermediate for zinc, copper, and magnesium; low and intermediate for calcium in men and women, respectively; and low for iron in women. In conclusion, the diet followed by T1DM patients may not have a sufficient content of different micronutrients. Therefore, an adequate intake of low-fat dairy products, fish, legumes, and vegetables should be encouraged as components of a healthier dietary pattern. Marisa Giorgini, Marilena Vitale, Lutgarda Bozzetto, Ornella Ciano, Angela Giacco, Anna Rivieccio, Ilaria Calabrese, Gabriele Riccardi, Angela A. Rivellese, and Giovanni Annuzzi Copyright © 2017 Marisa Giorgini et al. All rights reserved. A TRPM4 Inhibitor 9-Phenanthrol Inhibits Glucose- and Glucagon-Like Peptide 1-Induced Insulin Secretion from Rat Islets of Langerhans Mon, 02 Oct 2017 08:06:56 +0000 Pancreatic β-cells express several ion channels of the transient receptor potential family, which play important roles in mediating the stimulus-secretion coupling. One of these channels, the TRPM4 is a Ca2+-activated monovalent cation channel. This channel is inhibited by 9-phenanthrol, which also inhibits the TMEM16a Cl− channel, and activates the Ca2+-activated K+ channel, Kca3.1. The net effects of ion-channel modulation by 9-phenantherol on the insulin secretion remain unclear. We tested the effects of 9-phenanthrol on glucose- and GLP-1-induced insulin secretion from isolated rat islets in static incubations. When applied to the islets in the presence of 3.3 mM glucose, 9-phenanthrol caused a small increase in insulin secretion (~7% of the insulin secretion stimulated by 10 mM glucose). 10 μM 9-phenanthrol did not inhibit glucose- or GLP-1-induced insulin secretion. 20 μM and 30 μM 9-phenanthrol inhibited glucose-induced insulin secretion by ~80% and ~85%, respectively. Inhibition of the GLP-1-induced insulin secretion by 20 μM and 30 μM 9-phenanthrol was 65% and 94%, respectively. Our study shows that the major effect of 9-phenanthrol on the islets is a strong inhibition of insulin secretion, and we speculate that compounds related to 9-phenanthrol may be potentially useful in treating the pancreatogenous hyperinsulinemic hypoglycemia syndromes. Zuheng Ma, Anneli Björklund, and Md. Shahidul Islam Copyright © 2017 Zuheng Ma et al. All rights reserved. Changes in Proteinuria on the Risk of All-Cause Mortality in People with Diabetes or Prediabetes: A Prospective Cohort Study Wed, 27 Sep 2017 00:00:00 +0000 Background. Proteinuria has been related to all-cause mortality, showing regression or progression. However, few studies have focused on the relationship between proteinuria changes and all-cause mortality. The main purpose of this paper is to examine the associations between proteinuria changes and all-cause mortality in people with diabetes or prediabetes. Methods. Dipstick proteinuria at baseline and a 2-year follow-up were determined in the participants attending the Kailuan prospective cohort study. Participants were then divided into three categories: elevated proteinuria, stable proteinuria, and reduced proteinuria. Four Cox proportional hazard models were built to access the relations of proteinuria changes to all-cause mortality, adjusting for other confounding covariates. Results. A total of 17,878 participants were finally included in this study. There were 1193 deaths after a median follow-up of 6.69 years. After adjusting for major covariates and proteinuria at baseline, mortality risk was significantly associated with elevated proteinuria (hazard ratio (HR): 1.54, 95% confidence interval (CI): 1.33–1.79) and reduced proteinuria (HR: 0.70, 95% CI: 0.55–0.89), compared to those with stable proteinuria. Conclusion. Proteinuria changes were independently associated with mortality risk in either diabetic or prediabetic population. Yang Sun, Anxin Wang, Xiaoxue Liu, Zhaoping Su, Junjuan Li, Yanxia Luo, Shuohua Chen, Jianli Wang, Xia Li, Zhan Zhao, Huiping Zhu, Shouling Wu, and Xiuhua Guo Copyright © 2017 Yang Sun et al. All rights reserved. Role of the Gastrointestinal Tract Microbiome in the Pathophysiology of Diabetes Mellitus Tue, 26 Sep 2017 00:00:00 +0000 The incidence of diabetes mellitus is rapidly increasing throughout the world. Although the exact cause of the disease is not fully clear, perhaps, genetics, ethnic origin, obesity, age, and lifestyle are considered as few of many contributory factors for the disease pathogenesis. In recent years, the disease progression is particularly linked with functional and taxonomic alterations in the gastrointestinal tract microbiome. A change in microbial diversity, referred as microbial dysbiosis, alters the gut fermentation profile and intestinal wall integrity and causes metabolic endotoxemia, low-grade inflammation, autoimmunity, and other affiliated metabolic disorders. This article aims to summarize the role of the gut microbiome in the pathogenesis of diabetes. Additionally, we summarize gut microbial dysbiosis in preclinical and clinical diabetes cases reported in literature in the recent years. Muhammad U. Sohail, Asmaa Althani, Haseeb Anwar, Roberto Rizzi, and Hany E. Marei Copyright © 2017 Muhammad U. Sohail et al. All rights reserved. Fulminant Type 1 Diabetes in Children: A Multicenter Study in China Tue, 26 Sep 2017 00:00:00 +0000 Background. To investigate the hospital-based incidence of FT1D in Chinese children and compare the clinical feature with classical T1DM. Methods. A cross-sectional study with sixteen hospitals involved. We obtained 23 FT1D cases as group 1, acute-onset T1DM as group 2, and typical T1DM as group 3. Results. The incidence of FT1D was 1.56% in 16 participating hospitals. The mean age at the onset of group 1 was 2.00 (1.08, 6.51) years old, much younger than that of group 2 (6.11 (3.92, 9.50)) and group 3 (6.92 (4.17, 10.03)). In addition, significant differences were found between three groups: mean BMI and flu-like symptoms with fever and abdominal pain. Follow-up comparison of three groups from Beijing Children’s Hospital for at least one year showed that there is no significant difference between the three groups in terms of mean HbA1c levels and insulin injection dosages. Conclusion. FT1D onset age is much younger than that of classical T1D patients. The hospital-based incidence of FT1D in Chinese children was 1.56% in all new-onset T1DM. For the diagnosis, making FT1D alone into a subtype within type 1 diabetes may be meaningful. However, for the treatment and prognosis, such classification should not be helpful to the clinic. Yi Gu, Yi Wang, Pin Li, Haiyan Wei, Linqi Chen, Qianqi Liu, Yu Liu, Qiaozhi Yang, Xinran Cheng, Lanjie He, Liya Wei, Zhiying Zhu, Yongxing Chen, Fengyun Wang, Xing Shi, Yuxian Cheng, Yan Wei, Jianing Yu, and Chunxiu Gong Copyright © 2017 Yi Gu et al. All rights reserved. Reduced Inspiratory Muscle Strength in Patients with Type 2 Diabetes Mellitus and Obstructive Sleep Apnoea Mon, 25 Sep 2017 00:00:00 +0000 Background. Obstructive sleep apnoea (OSA) is related to type 2 diabetes (T2DM), and it may be associated with reduced inspiratory muscle strength (IMS). The aim of this study was to investigate the IMS in patients with T2DM, with or without OSA. Methods. Patients with T2DM with OSA () and without OSA () were included. The maximum IMS was tested using the POWERbreathe KH2 device. Reference IMS values were data calculated using an algorithm based on general populations and adjusted for age and gender. Results. There was no difference in IMS between the OSA group (median (range) 77 (35–124) cmH2O) and the non-OSA group (84 (33–122) cmH2O) (). The IMS values were reduced in the OSA group compared with the reference values (92.9 (62.3–100.0) cmH2O) (), whereas the non-OSA group did not have reduced IMS. When the IMS values of all T2DM patients were compared with reference values, the IMS values were 79 (33–124) cmH2O and 93.8 (62.3–102.4) cmH2O, respectively (). Conclusion. No difference in IMS between patients with T2DM with or without OSA was found. However, patients with T2DM and OSA had reduced IMS compared with age- and gender-matched references whereas the non-OSA group did not have reduced IMS. Thomas Rehling, Anne Margareta Banghøj, Marie Hvelplund Kristiansen, Lise Tarnow, and Stig Molsted Copyright © 2017 Thomas Rehling et al. All rights reserved. Sympathetic Denervation Accelerates Wound Contraction but Inhibits Reepithelialization and Pericyte Proliferation in Diabetic Mice Sun, 24 Sep 2017 00:00:00 +0000 Previous studies focused on the effects of sympathetic denervation with 6-hydroxydopamine (6-OHDA) on nondiabetic wounds, but the effects of 6-OHDA on diabetic wounds have not been previously reported. In this study, treated mice received intraperitoneal 6-OHDA, and control mice received intraperitoneal injections of normal saline. Full-thickness wounds were established on the backs of mice. The wounds were sectioned (four mice per group) for analysis at 2, 5, 7, 10, 14, 17, and 21 days after injury. The wound areas in the control group were larger than those in the treatment group. Histological scores for epidermal and dermal regeneration were reduced in the 6-OHDA-treated group on day 21. The mast cells (MCs) in each field decreased after sympathectomy on days 17 and 21. The expression levels of norepinephrine, epidermal growth factor (EGF), interleukin-1 beta, NG2 proteoglycan, and desmin in the treatment group were less than those in the control group. In conclusion, 6-OHDA delays reepithelialization during wound healing in diabetic mice by decreasing EGF, but increases wound contraction by reducing IL-1β levels and the number of MCs. Besides, 6-OHDA led to reduced pericyte proliferation in diabetic wounds, which might explain the vascular dysfunction after sympathetic nerve loss in diabetic wounds. Zhifang Zheng, Yu Wan, Yishu Liu, Yu Yang, Jianbing Tang, Wenhua Huang, and Biao Cheng Copyright © 2017 Zhifang Zheng et al. All rights reserved. Corrigendum to “Optimal Hemoglobin A1c Levels for Screening of Diabetes and Prediabetes in the Japanese Population” Sun, 24 Sep 2017 00:00:00 +0000 Masanori Shimodaira, Shinji Okaniwa, Norinao Hanyu, and Tomohiro Nakayama Copyright © 2017 Masanori Shimodaira et al. All rights reserved. Correlates of Calcaneal Quantitative Ultrasound Parameters in Patients with Diabetes: The Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes Tue, 19 Sep 2017 00:00:00 +0000 Objective. Quantitative ultrasound (QUS) provides an estimate of bone mineral density (BMD) and also evaluates bone quality, which has been related to increased fracture risk in people with diabetes. This study aimed at assessing the correlates of calcaneal QUS parameters in diabetic subjects encompassing various degrees of micro and macrovascular complications and a wide-range of peripheral nerve function. Methods. Four hundred consecutive diabetic patients were examined by QUS to obtain values of broadband ultrasound attenuation (BUA), the speed of sound (SOS), quantitative ultrasound index (QUI), and BMD. Results. Among surrogate measures of complications, sensory and motor nerve amplitude and heart rate response to cough test and standing correlated with QUS parameters at univariate analysis, together with age, body mass index (BMI), waist circumference, lipid profile, and renal function. Multivariate analysis revealed that BUA, SOS, QUI, and BMD were independently associated with age, male gender, hemoglobin A1c, BMI (or fat, but not fat-free mass), and somatic and autonomic nerve function parameters. Conclusions. These data indicate that peripheral nerve dysfunction is associated with worse QUS parameters, possibly contributing to increased fracture risk in diabetes. The positive relation of QUS measures with adiposity needs further investigation. This trial is registered with (NCT01600924). Francesco Conti, Stefano Balducci, Luca Pugliese, Valeria D’Errico, Martina Vitale, Elena Alessi, Gerardo Salerno, Carla Iacobini, Stefano Menini, Lucilla Bollanti, Antonio Nicolucci, and Giuseppe Pugliese Copyright © 2017 Francesco Conti et al. All rights reserved. Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus Thu, 14 Sep 2017 07:08:05 +0000 Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM). BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM. Ceren Eyileten, Agnieszka Kaplon-Cieslicka, Dagmara Mirowska-Guzel, Lukasz Malek, and Marek Postula Copyright © 2017 Ceren Eyileten et al. All rights reserved. Trajectories of Postload Plasma Glucose in the Development of Type 2 Diabetes in Japanese Adults Thu, 14 Sep 2017 00:00:00 +0000 We aimed to clarify how the trajectories of 1-hour postload plasma glucose (PG) and 2-hour PG were different in the development of type 2 diabetes. Using data of repeated health checkups in Japanese workers from April 2006 to March 2016, longitudinal changes of fasting, 1-hour, and 2-hour PG on the oral glucose tolerance test were analyzed with a linear mixed effects model. Of the 1464 nondiabetic subjects at baseline, 112 subjects progressed to type 2 diabetes during the observation period (progressors). In progressors, 1-hour PG and 2-hour PG showed gradual increases with slopes of 1.33 ± 0.2 and 0.58 ± 0.2 mg/dL/year, respectively, followed by a steep increase by which they attained diabetes. Until immediately before the diabetes transition, age- and sex-adjusted mean level of 2-hour PG was 149 ± 2.7 mg/dL, 34 ± 2.7 (30%) higher compared to nonprogressors, while that of 1-hour PG was 206 ± 4.1 mg/dL, 60 ± 4.3 mg/dL (41%) higher compared to nonprogressors. In conclusion, diabetes transition was preceded by a mild elevation of 2-hour PG for several years or more. The elevation in 1-hour PG was larger than that of 2-hour PG until immediately before the transition to diabetes. Rie Oka, Kyoko Shibata, Masaru Sakurai, Mitsuhiro Kometani, Masakazu Yamagishi, Kenichi Yoshimura, and Takashi Yoneda Copyright © 2017 Rie Oka et al. All rights reserved. Akt/mTOR Role in Human Foetoplacental Vascular Insulin Resistance in Diseases of Pregnancy Thu, 14 Sep 2017 00:00:00 +0000 Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium. Roberto Villalobos-Labra, Luis Silva, Mario Subiabre, Joaquín Araos, Rocío Salsoso, Bárbara Fuenzalida, Tamara Sáez, Fernando Toledo, Marcelo González, Claudia Quezada, Fabián Pardo, Delia I. Chiarello, Andrea Leiva, and Luis Sobrevia Copyright © 2017 Roberto Villalobos-Labra et al. All rights reserved. Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes? Sun, 10 Sep 2017 00:00:00 +0000 Background. The incretin effect is impaired in patients with type 2 diabetes. Aim. To assess the relation between the incretin hormone GLP-1 and the prediabetic subtypes: impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and the combined IFG/IGT to investigate whether a low GLP-1 response may be a predictor of prediabetes in adults. Method. 298 articles were found using a broad search phrase on the PubMed database and after the assessment of titles and abstracts 19 articles were included. Results and Discussion. Studies assessing i-IFG/IFG and i-IGT/IGT found both increased, unaltered, and reduced GLP-1 levels. Studies assessing IFG/IGT found unaltered or reduced GLP-1 levels. When assessing the five studies with the largest sample size, it clearly suggests a decreased GLP-1 response in IFG/IGT subjects. Several other factors (BMI, glucagon, age, and nonesterified fatty acids (NEFA)), including medications (metformin), may also influence the secretion of GLP-1. Conclusion. This review suggests that the GLP-1 response is a variable in prediabetes possibly due to a varying GLP-1-secreting profile during the development and progression of type 2 diabetes or difference in the measurement technique. Longitudinal prospective studies are needed to assess whether a reduced GLP-1 response is a predictor of diabetes. Matthias Ploug Larsen and Signe Sørensen Torekov Copyright © 2017 Matthias Ploug Larsen and Signe Sørensen Torekov. All rights reserved. Effects of Renal Denervation on Insulin Sensitivity and Inflammatory Markers in Nondiabetic Patients with Treatment-Resistant Hypertension Thu, 07 Sep 2017 02:56:03 +0000 Increased sympathetic activity is important in the pathogenesis of hypertension and insulin resistance. Afferent signaling from the kidneys elevates the central sympathetic drive. We investigated the effect of catheter-based renal sympathetic denervation (RDN) on glucose metabolism, inflammatory markers, and blood pressure in nondiabetic patients with treatment-resistant hypertension. Eight subjects were included in an open-labelled study. Each patient was studied before and 6 months after RDN. Endogenous glucose production was assessed by a 3-3H glucose tracer, insulin sensitivity was examined by hyperinsulinemic euglycemic clamp, hormones and inflammatory markers were analyzed, and blood pressure was measured by office blood pressure readings and 24-hour ambulatory blood pressure monitoring. Insulin sensitivity (-value) increased nonsignificantly from 2.68 ± 0.28 to 3.07 ± 0.41 (). A significant inverse correlation between the increase in -value and BMI 6 months after RDN () was found, suggesting beneficial effects on leaner subjects. Blood pressure decreased significantly, but there were no changes in hormones, inflammatory markers, or endogenous glucose production. Our results indicate that RDN may improve insulin sensitivity in some patients with treatment-resistant hypertension, albeit confirmation of these indications of beneficial effects on leaner subjects awaits the outcome of larger randomized controlled studies. Ulla Kampmann, Ole N. Mathiassen, Kent L. Christensen, Niels H. Buus, Mette Bjerre, Henrik Vase, Niels Møller, Anne Kaltoft, and Per L. Poulsen Copyright © 2017 Ulla Kampmann et al. All rights reserved. Vitamin D Supplementation Improves Mood in Women with Type 2 Diabetes Thu, 07 Sep 2017 02:31:18 +0000 Objective. The aim of this study was to determine the effect of vitamin D supplementation on improving mood (depression and anxiety) and health status (mental and physical) in women with type 2 diabetes mellitus (T2DM). Methods. Fifty women with T2DM and significant depressive symptomology were enrolled into the “Sunshine Study,” where weekly vitamin D supplementation (ergocalciferol, 50,000 IU) was given to all participants for six months. The main outcomes included (1) depression (Center for Epidemiologic Studies Depression, CES-D, and Patient Health Questionnaire, PHQ-9), (2) anxiety (State-Trait Anxiety), and (3) health status (Short Form, SF-12). Results. Forty-six women (92%) completed all visits. There was a significant decrease in depression (CES-D and PHQ-9, ) and anxiety (state and trait, ). An improvement in mental health status (SF-12, ) was also found. After controlling for covariates (race, season of enrollment, baseline vitamin D, baseline depression (PHQ-9), and body mass index), the decline in depression remained significant (CES-D, ). There was a trend for a better response to supplementation for women who were not taking medications for mood (antidepressants or anxiolytics) (). Conclusions. Randomized trials to confirm that vitamin D supplementation can improve mood and health status in T2DM women are needed. Sue Penckofer, Mary Byrn, William Adams, Mary Ann Emanuele, Patricia Mumby, Joanne Kouba, and Diane E. Wallis Copyright © 2017 Sue Penckofer et al. All rights reserved. Increased Serum ANGPTL8 Concentrations in Patients with Prediabetes and Type 2 Diabetes Thu, 07 Sep 2017 00:00:00 +0000 The objectives of the study were to investigate serum ANGPTL8 concentrations in different glucose metabolic statuses and to explore the correlations between serum ANGPTL8 levels and various metabolic parameters. Serum ANGPTL8 levels were determined using ELISA in 22 subjects with NGT (normal glucose tolerance), 74 subjects with IGR (impaired glucose regulation), and 33 subjects with T2DM (type 2 diabetes mellitus). Subjects with IFG, IGT, CGI, and T2DM had higher levels of serum ANGPTL8 than subjects with NGT. Serum ANGPTL8 was positively correlated with FPG, fasting C-peptide, and postprandial C-peptide and negatively correlated with BETA/IR when adjusted for age and BMI. Multivariate analysis suggested FPG and fasting C-peptide as independent factors associated with serum ANGPTL8 levels. Serum ANGPTL8 concentrations were significantly increased in IGR and T2DM. Serum ANGPTL8 might play a role in the pathological mechanism of glucose intolerance. Yanhua Yin, Xiaoying Ding, Liang Peng, Yanqiang Hou, Yunxia Ling, Mingyu Gu, Yufan Wang, Yongde Peng, and Haiyan Sun Copyright © 2017 Yanhua Yin et al. All rights reserved. The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective Thu, 07 Sep 2017 00:00:00 +0000 Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorders, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GHS-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune systems to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D). Jéssica Aparecida da Silva Pereira, Felipe Corrêa da Silva, and Pedro Manoel Mendes de Moraes-Vieira Copyright © 2017 Jéssica Aparecida da Silva Pereira et al. All rights reserved. High Prevalence of Autoimmune Diabetes and Poor Glycaemic Control among Adults in Madagascar: A Brief Report from a Humanitarian Health Campaign in Ambanja Wed, 06 Sep 2017 00:00:00 +0000 Madagascar is a geographically isolated country considered a biodiversity hotspot with unique genomics. Both the low-income and the geographical isolation represent risk factors for the development of diabetes. During a humanitarian health campaign conducted in Ambanja, a rural city in the northern part of Madagascar, we identified 42 adult subjects with diabetes and compared their features to 24 randomly enrolled healthy controls. 42.9% () of diabetic subjects showed HbA1c values ≥ 9.0%. Unexpectedly, waist circumference and BMI were similar in people with diabetes and controls. Different from the healthy controls, diabetic subjects showed a low prevalence of obesity (5.7% versus 30%, ). Accordingly, we found a high prevalence of autoimmune diabetes as 12% of people with diabetes showed positivity for the autoantibody against glutamic acid decarboxylase. Diabetic subjects with positive autoantibody had higher HbA1c values (11.3 ± 4.1% versus 8.3 ± 2.6%, ) compared to diabetic subjects with negative autoantibody. In conclusion, here we describe the presence of diabetes and its features in a rural area of Northern Madagascar, documenting poor glycaemic control and a high prevalence of autoimmune diabetes. These data highlight that the diabetes epidemic involves every corner of the world possibly with different patterns and features. Ernesto Maddaloni, Giovanlorenzo Pastore, Marco Giuseppe Del Buono, Aldostefano Porcari, Mario Fittipaldi, Francesco Garilli, Claudio Tiberti, Silvia Angeletti, Paolo Pozzilli, Giovanni Mottini, and Nicola Napoli Copyright © 2017 Ernesto Maddaloni et al. All rights reserved. Low Levels of Usual Physical Activity Are Associated with Higher 24 h Blood Pressure in Type 2 Diabetes Mellitus in a Cross-Sectional Study Wed, 06 Sep 2017 00:00:00 +0000 The aim of this study is to evaluate the association between usual physical activity and 24 h blood pressure (BP) profile in people with type 2 diabetes mellitus (DM). This is a cross-sectional study of 151 participants with type 2 DM. Usual physical activity was assessed by step counting and self-reported questionnaire. BP was measured in office and by 24 h ambulatory BP monitoring (ABPM; 24 h, daytime and nighttime). Mean participant age was 61.1 ± 8.4 years, 64% was women, and mean duration of diabetes was 14.3 ± 8.5 years. Ninety-two percent of participants had hypertension, and office BP was 138 ± 18/78 ± 10 mmHg. Inverse correlations were observed between step count and 24 h BP (systolic, ; ), daytime BP (systolic, ; ), and nighttime BP (pulse pressure, ; ). People were categorized into tertiles of daily step count, and the 1st tertile had higher 24 h systolic BP, daytime systolic BP, daytime mean BP, and daytime systolic BP load than those in the other tertiles, even after adjusting for age and HbA1c. Participants with type 2 DM and low levels of physical activity exhibit higher 24 h and daytime systolic ambulatory BP values as compared with those who performed more steps per day, even after adjustments for confounding factors. Alessandra Teixeira Neto Zucatti, Tatiana Pedroso de Paula, Luciana Verçoza Viana, Rafael DallAgnol, Felipe Vogt Cureau, Mirela Jobim Azevedo, Jorge Luiz Gross, Beatriz D. Schaan, and Cristiane Bauermann Leitao Copyright © 2017 Alessandra Teixeira Neto Zucatti et al. All rights reserved.