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(searched for: Microalbuminuria in Type 2 Diabetes Mellitus and Glycemic Control)
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, Sylvie A. Ahn, Shaukat Sadikot, Michel F. Rousseau
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Volume 14, pp 1503-1509; doi:10.1016/j.dsx.2020.07.027

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M.D.; Mohamed Halawa Salah Shelbaya, M.D. Merhan Nasr
The Medical Journal of Cairo University, Volume 88, pp 1413-1421; doi:10.21608/mjcu.2020.110954

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Nikoletta Proudan, Murray B Gordon
Journal of the Endocrine Society, Volume 4; doi:10.1210/jendso/bvaa046.1550

Abstract:
Myotonic dystrophy (MD) is a multisystemic, autosomal dominant disorder associated with progressive muscle weakness, premature cataracts, frontal baldness, and cardiac disturbances. MD has been associated with several endocrinopathies including primary testicular failure, autoimmune endocrinopathies (hypothyroidism, hyperthyroidism, multinodular goiter, and Addison’s disease), thyroid carcinoma (primarily papillary), insulin resistance, and type 2 DM. Development of diabetes is thought to be related to formation of an insulin-resistant receptor because of aberrant regulation of mRNA. We describe the first reported case of a patient with MD associated with type I diabetes mellitus, Hashimoto’s thyroiditis with hypothyroidism, and follicular variant of papillary thyroid cancer. A 49-year-old female presented with acute congestive heart failure. The patient had history of type I DM diagnosed at the age of 26, complicated by mild background retinopathy, peripheral neuropathy, and nephropathy with microalbuminuria. The patient first noticed proximal muscle weakness 1 year ago that gradually progressed resulting in multiple falls. She had history of bilateral cataracts status post cataract extraction at age 26. She also had progressive dysphagia requiring PEG placement, and cognitive dysfunction with mood disorder and depression. Family history was significant for myotonic dystrophy in both maternal aunt and uncle as well as 2 cousins. EMG confirmed myotonia however genetic testing was not obtained due to cost. Due to her cognitive dysfunction and depression, she had difficult to control diabetes with HbA1c of 9.9%, and multiple previous admissions for DKA. She was status post total thyroidectomy in 2008 for follicular variant of papillary carcinoma and Hashimoto’s thyroiditis followed by I-131 therapy in 2009 and maintained on levothyroxine suppression therapy. Most recent Tg and Tg Ab were undetectable. On physical exam, the patient had a narrow, sallow face with temporal muscle atrophy, percussion myoclonus involving the thenar eminence of the hands, but no frontal balding. Work up showed LVEF of 20-24% with regional hypokinesis that led to catherization and PCI to LAD. The patient had recurrent NSTEMI which eventually resulted in CABG 1 year after presentation. The association of autoimmune endocrinopathies, thyroid carcinoma and MD suggests a possible cause and effect relationship between these disorders. In patients with diabetes and MD, previously described insulin resistance as well as cognitive dysfunction can hinder good glycemic control increasing risk for complications. Although patients with MD are typically treated by neurologists, evaluation and therapy of endocrine dysfunctions are also necessary.
X Y Zheng, S H Luo, X Y Wei, P Ling, H Y Ai, Z Y Liu, Q Y Lin, J Lü, B Yao, J H Yan, et al.
Published: 18 February 2020
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Wen-Chan Chiu, Yun-Ru Lai, Ben-Chung Cheng, Chih-Cheng Huang, Jung-Fu Chen,
Published: 25 January 2020
BioMed Research International, Volume 2020, pp 1-8; doi:10.1155/2020/7462158

Abstract:
Background. Glycemic variability is associated with higher risk of microvascular complications in patients with type 2 diabetes. Aim. To test the hypothesis that glycemic variability can contribute to progression to macroalbuminuria in normal or microalbuminuria in patients with type 2 diabetes. Design. This prospective study enrolled 193 patients with type 2 diabetes at a tertiary medical center. Methods. For each patient, the intrapersonal glycemic variability (mean, SD, and coefficient of variation of HbA1c) was calculated using all measurements obtained three years before the study. Patients were divided into four groups stratified by both urine albumin/creatinine ratio and HbA1c-SD. The presence of macroalbuminuria was assessed with Kaplan–Meier plots and compared by log-rank test. Results. Of the 193 patients, 83 patients were in the macroalbuminuria state. Patients in the initial macroalbuminuria group after enrollment had the highest diabetes duration, mean, CV-HbA1c and HbA1c-SD, and uric acid level, and the lowest estimate glomerular filtration rate, followed by subsequent macroalbuminuria and without macroalbuminuria groups. Patients with microalbuminuria and high HbA1c-SD showed the highest progression rate to macroalbuminuria, after a six-year follow-up study by Kaplan–Meier Plots and compared by log-rank test. Conclusions. Higher HbA1C variability is more likely to progress to macroalbuminuria in those patients who are already in a microalbuminuria state. We recommend that clinicians should aggressively control blood glucose to an acceptable range and avoid blood glucose fluctuations by individualized treatment to prevent renal status progression.
Asad Ullah, Rozi Khan, Jaffar Khan, Muhammad Saleem Panezai, Asad Khan Kakar, Muhammad Samsoor Zarak
Archives of Nephrology and Urology, Volume 3, pp 5-16; doi:10.26502/anu.2644-2833015

Abstract:
Objective: To determine the frequency of microalbuminuria in Type 2 Diabetes Mellitus with good glycemic control. Introduction: Diabetes Mellitus is a chronic illness, frequently not diagnosed until complications appear. Microalbuminuria is a renal marker of generalized vascular endothelial damage and early atherosclerosis. Patients with microalbuminuria are at increased risk of microvascular and macrovascular complications of Diabetes Mellitus like myocardial infarction, stroke, and nephropathy. Poor glycemic control increases the risk of microalbuminuria. Methodology: A cross-sectional study is conducted at the Department of Medicine, Bolan Medical College/ Sandeman Provincial Hospital Quetta, Pakistan. The duration of the study is six months from September 2016 to March 2017. A total of 140 Type 2 DM patients with good glycemic control is included in this study. 63 (45%) were female, and 77 (55%) were male with a mean age of 44.47 ± 4.99 years. The mean duration of DM is found to be 4.21 ± 0.94 years. The mean HbA1c level was found to be 6.74 ± 0.17. 21 patients (15%) were found to have microalbuminuria. Conclusion: There is an association of microalbuminuria in diabetic patients with good glycemic control; however, the prevalence is low, but it is still positive. Uncontrolled DM is strongly associated with the prevalence of microalbuminuria. Screening for microalbuminuria and HbA1c test should be done both in new and already diagnosed type 2 diabetic patients as an early marker of renal dysfunction and glycemic control.
Yanli Li, Min Yi, Xiaoyi Deng, Singla Sethiel Mosha, Wangen Li, Xiaodan Zhang
Published: 22 November 2019
Abstract:
Background : Diabetes mellitus (DM) and thyroid dysfunction (TD) are two closely associated disorders. The coexistence of TD could adversely influence metabolic control and even increase the long-term mortality in patients with DM. The objective of the present study was to investigate the prevalence and risk factors of TD in patients with type 2 DM (T2DM). Methods : This is an observational cross-sectional study. A total of 340 patients with newly diagnosed T2DM who were admitted to ward of endocrinology department were included for analysis. Thyroid function was examined and its relationship with demographic, metabolic and diabetes-related parameters were evaluated Results : The prevalence of TD was 21.2% in the total population. The low T3 syndrome was the most frequent TD, in 14.7% of patients. Low FT3 level was associated with diabetic complications including presence of diabetic ketosis (DK) or diabetic ketoacidosis (DKA) (r = -0.388, P ≤ 0.001) and microalbuminuria (r = -0.302, P ≤ 0.001). Metabolic and demographic factors, including age, glycemic control and insulin resistance also correlated with levels of thyroid hormones. DK or DKA (OR = 6.161, P ≤ 0.001) and microalbuminuria (OR = 3.950, P = 0.002) were risk factors of low T3 syndrome. Conclusion : TD is not rarely seen in patients with newly diagnosed T2DM. Diabetic complications and diabetes-related metabolic and demographic factors are related to the presence of TD.
Yanli Li, Min Yi, Xiaoyi Deng, Singla Sethiel Mosha, Wangen Li, Xiaodan Zhang
Published: 4 November 2019
Abstract:
Background : Diabetes mellitus (DM) and thyroid dysfunction (TD) are two closely associated disorders. The coexistence of TD could adversely influence metabolic control and even increase the long-term mortality in patients with DM. The objective of the present study was to investigate the prevalence and risk factors of TD in patients with type 2 DM (T2DM). Methods : This is an observational cross-sectional study. A total of 340 patients with newly diagnosed T2DM who were admitted to ward of endocrinology department were included for analysis. Thyroid function was examined and its relationship with demographic, metabolic and diabetes-related parameters were evaluated Results : The prevalence of TD was 21.2% in the total population. The low T3 syndrome was the most frequent TD, in 14.7% of patients. Low FT3 level was associated with diabetic complications including presence of diabetic ketosis (DK) or diabetic ketoacidosis (DKA) (r = -0.388, P ≤ 0.001) and microalbuminuria (r = -0.302, P ≤ 0.001). Metabolic and demographic factors, including age, glycemic control and insulin resistance also correlated with levels of thyroid hormones. DK or DKA (OR = 6.161, P ≤ 0.001) and microalbuminuria (OR = 3.950, P = 0.002) were risk factors of low T3 syndrome. Conclusion : TD is not rarely seen in patients with newly diagnosed T2DM. Diabetic complications and diabetes-related metabolic and demographic factors are related to the presence of TD.
Youssef Khalel Ahmed, Amin Mahmoud Amin Hegazy, Mohammed Abdel-Hamed Keder, Mohamed Ahmed Mohamed Moustafa
The Egyptian Journal of Hospital Medicine, Volume 77, pp 5579-5588; doi:10.21608/ejhm.2019.61456

The publisher has not yet granted permission to display this abstract.
, I. I. Mustafaev,
Cardiovascular Therapy and Prevention, Volume 18; doi:10.15829/1728-8800-2019-3-48-56

Abstract:
Aim. To study the relationship of chronic kidney disease parameters with glycemic control, subclinical and clinical signs of cardiovascular diseases and laboratory parameters.Material and methods. The study included 528 patients with type 2 diabetes mellitus (T2DM) aged 30-69 years. All respondents answered questions from the ARIC questionnaire about T2DM and cardiovascular diseases. We determined the ankle-brachial index, sonographic left ventricular hypertrophy, intima-media thickness and defined hypertensive, diabetic angiopathy and polyneuropathy. The levels of glycemia, lipid spectrum, creatinine, uric acid, glycohemoglobin were evaluted. Glomerular filtration rate (GFR) was calculated using the Cockroft-Gault method, and microalbuminuria (MAU) was determined using Micral tests.Results. Glycohemoglobin did not depend on MAU (p=0,564), a decrease in GFR was accompanied by an improvement in glycemic control (p=0,393). There was a direct association between MAU and the duration of diabetes (p=0,001), in patients with a longer course of the disease GFR was reduced (p=0,001). With increasing of systolic blood pressure, MAU progressed (p=0,016), while GFR decreased (pConclusion. Reduction of GFR and MAU are the major risk factors for cardiovascular diseases in the Azerbaijani population with T2DM. We suppose that periodic monitoring of these parameters for primary and secondary prevention of diabetic nephropathy plays an important role.
Mesbah Uddin Ahmed, Sheuly Ferdousi, Tania Nasreen, Saiful Islam, Quddusur Rahman, Shahjada Selim, Debatosh Paul, Tuhin Sultana
Current Research in Diabetes & Obesity Journal, Volume 10, pp 001-004; doi:10.19080/crdoj.2019.10.555795

Abstract:
Diabetes mellitus is a clinical condition characterized by increased blood glucose level (hyperglycemia) due to insufficient or inefficient (incompetent)insulin [1]. The incidence of diabetes is rising. As a result, Diabetic nephropathy is more common now a days and an important cause of morbidity and mortality in chronic kidney disease and end-stage kidney disease (ESKD) or failure [2]. Improved glycemic control has been demonstrated to reduce micro and macro vascular complications in patients with diabetes. Glycated hemoglobin (HbA1c) is the preferred and widely utilized biomarker of glycemic control in subjects with diabetes with higher concentrations of glucose [3].
Mayssa I. Ali, Lubna A. Fawaz, , Zeinab A. Nour, Radwa M. Elsayed
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Volume 13, pp 1971-1973; doi:10.1016/j.dsx.2019.04.040

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, Santosh Timalsina, Sanat Chalise, Anita Yadav, Ashish Kumar Bhattarai
Journal of Chitwan Medical College, Volume 9, pp 2-7; doi:10.3126/jcmc.v9i1.23775

Abstract:
Background: Diabetes mellitus has become one of the biggest health problems of this era. The resultant microvascular and macrovascular complications add to significant amount of morbidity and mortality. Urine microalbumin is considered as an early marker for microvascular compli­cations among diabetic patients. The aim of this study was to find out the prevalence of microalbuminuria among type 2 diabetic patients attending Kathmandu Medical College and its relation with glycemic control, age, sex, duration of diabetes. Methods: A total of 208 previously diagnosed type 2 diabetic patients at­tending medical outpatient department of Kathmandu Medical College, Sinamangal were included in the study over a period of 1 year (October 2017 - September 2018). Fasting and 2-hour postprandial venous blood for blood glucose and HbA1c measurement and early morning urine sam­ple (after overnight fast) was collected for detection of microalbuminuria. Statistical analysis was done using SPSS version 23. Results: The prevalence of microalbuminuria among the study population (mean age: 54.22 ± 11.76 years, mean HbA1c: 7.62 ± 1.53 %) was 42.8%. Microalbuminuria had significant correlation with HbA1c and duration of diabetes (p
, Sabrina Ait Gacem, Syed K. Zaidi
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Volume 13, pp 1491-1496; doi:10.1016/j.dsx.2019.02.017

The publisher has not yet granted permission to display this abstract.
Theodora Stratigou, , Stavroula Koutroumpi, Barbara Vlassopoulou, Theofanis Apostolou, Stylianos Tsagarakis, George Ioannidis
Experimental and Clinical Endocrinology & Diabetes, Volume 129, pp 276-282; doi:10.1055/a-0848-8076

The publisher has not yet granted permission to display this abstract.
Diabetology & Metabolic Syndrome, Volume 11; doi:10.1186/s13098-019-0399-9

Abstract:
Polymorphisms in the gene encoding methylenetetrahydrofolate reductase (MTHFR) have been investigated as risk factors for microvascular complications of diabetes; however, simultaneous analysis of these polymorphisms and the methylation pattern of the gene has never been conducted. The objective of the present study was to evaluate the simultaneous relationship between MTHFR methylation and MTHFR C6TT7 and A1298C polymorphisms with metabolic, inflammatory and oxidative stress parameters related to microvascular complications, diabetic retinopathy (DR) and diabetic nephropathy (DN) in diabetic patients. A total of 107 patients who were diagnosed in the previous 5 to 10 years were recruited and divided into groups with complications (DR and/or DN) or without complications. Methylation analysis of the gene promoter was conducted using the MSP technique, and analysis of the A1298C and C677T polymorphisms was conducted using the restriction fragment length polymorphism (RFLP) assay. Microalbuminuria was determined using urine samples, and other analytes of interest were determined in blood samples using commercial kits. The Mann-Whitney and Chi square statistical tests were used with significance considered at p < 0.05. Subjects with a hypermethylated profile and the 1298AA genotype showed the highest levels of blood glucose (p = 0.03), total cholesterol (p = 0.0001) and LDL cholesterol (p = 0.0006). The same profile was associated with higher levels of HbA1c (p = 0.025), glycemia (p = 0.04) and total cholesterol (0.004) in the control group and total cholesterol (p = 0.005) and LDL cholesterol (p = 0.002) in the complications group. Serum creatinine was higher in subjects in the hypermethylated group with the genotype 677CC only in the control group (p = 0.0020). The methylated profile in presence of 677CC + 1298AA and the 677CT/TT +1298AA haplotypes showed higher levels of total cholesterol (p = 0.0024; 0.0031) and LDL cholesterol (p = 0.0060; 0.0125) than 1298AC/CC carriers. The fasting glycemia was higher in hypermethylated profile in the presence of 677CC/1298AA haplotype (p = 0.0077). The hypermethylated methylation profile associated with the 1298AA genotype appeared to be connected to higher values of glycemia, total cholesterol and LDL cholesterol.
Taqwaa Sueud, Najah R. Hadi, Raed Abdulameer, Dina A. Jamil,
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Volume 13, pp 564-568; doi:10.1016/j.dsx.2018.11.022

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Ugo Nnenna Chikani, Chinwe Flora Ogugua, Maryann Ugochi Ibekwe, Thomas Ngwieri, Holley Allen
Published: 1 January 2019
Annals of African Medicine, Volume 18, pp 200-205; doi:10.4103/aam.aam_5_19

Abstract:
Background: Clinically evident microvascular complications are rarely seen among children and adolescents with type 1 diabetes mellitus (T1DM), although early signs develop during childhood and accelerate during puberty. Aim: The aim of this study was to determine the prevalence of early signs of microvascular complications in children and adolescents aged 9–19 years with a short duration of T1DM by screening for retinopathy and nephropathy. Methods: A cross-sectional study and participants were consecutively enrolled from the Endocrinology Clinic at Federal Teaching Hospital, Abakaliki. Physical examination and mydriatic ophthalmoscopy were conducted. Three early morning spot urine specimens for albumin/creatinine ratio were estimated 3 months apart. Serum creatinine levels were estimated, and the glomerular filtration rate was calculated. Glycosylated hemoglobin (HbA1c) was determined. Results: Twenty-four individuals participated, 15 (62.5%) were male and the mean age at diagnosis was 12.4 ± 2.3 years. The mean duration of diabetes was 23.8 ± 20.6 months. The mean HbA1c was 11.4%. Retinopathy was seen in 16.7%, whereas 33.3% had microalbuminuria. Blood pressure range was within the 50th–90th percentile for all the participants. Conclusion: The study outcome demonstrated a high prevalence of early signs of microvascular complications such as retinopathy and nephropathy among youths with short duration of T1DM. Poor glycemic control, if not halted, is associated with early signs of microvascular complications which may become clinically evident; contrary to the belief that they are rare in childhood. RésuméObjectif: abstrait Déterminer la prévalence des signes précoces de complications microvasculaires chez les adolescents âgés de 9 à 19 ans ayant une courte durée de T1DM par dépistage de la rétinopathie et de la néphropathie. Méthodes: Une étude transversale et des sujets ont été inscrits consécutivement de la clinique d'endocrinologie à l'hôpital fédéral d'enseignement Abakaliki.L'examen physique et l'ophtalmose mydriatique ont été menés. Trois spécimens d'urine de tache tôt le matin pour le rapport d'albumine/créatinine ont été estimés 3 mois d'intervalle.Des niveaux de créatinine de sérum ont été estimés et le taux glomerular de filtration calculé.L'hémoglobine glycosylated (HbA1c) a été déterminée. Résultats: 24 sujets ont participé, Quinze (62,5%) étaient des mâles et l'âge moyen au diagnostic était de 12,4 à 2,3 ans.La durée moyenne du diabète était de 23,8 à 20,6 mois. Leur HbA1c moyen était de 11,4%.La rétinopathie a été vue dans 16.7% tandis que 33.3% a eu le microalbuminuria. La tension artérielle se situe entre le 50e et le 90e percentile pour tous les participants. Conclusion: Les signes de complication microvasculaire se manifestent tôt chez les enfants et les adolescents atteints de TIDM dans le sud-est du Nigeria.Contrairement à la croyance que les complications microvasculaires cliniquement évidentes sont rarement vues parmi des enfants avec T1DM.Un mauvais contrôle glycémique et la puberté sont des facteurs de risque importants.
Pragati Garg, Smriti Mishra,
International Journal of Ophthalmic Research, Volume 5, pp 308-313; doi:10.17554/j.issn.2409-5680.2019.05.87

Abstract:
AIM: The present study was carried out with an aim to study the concordance and correlation of microalbuminuria, dyslipidemia with the severity of Diabetic Retinopathy in type II diabetes mellitus patient and to provide a possible basis for explanation of mechanisms governing this relationship.MATERIAL AND METHOD: The study was conducted in a tertiary care hospital in North India.The patients underwent thorough history and ocular evaluation.The patients included in the study were advised to undergo biochemical investigations for Blood sugar, Urinary albumin to creatinine ratio in a random spot collection of urine and Lipid profile. Patients with acute or chronic renal failure, Opaque/hazy ocular media preventing fundus visualization, Co-existing ocular disorders likely to mask the findings of diabetic retinopathy, Patients with presence of any of the confounding factors, like fever, active systemic infections, exercise, high protein intake, accelerated hypertension, congestive heart failure, patients not willing to participate in the study were excluded from the study.RESULTS: 444 subjects of either gender were included in our study, out of which 236 patients were females and the rest were males. Majority of the patients lied in the age group of 41-60 years (54.73%) followed by 61-80 years (29.28%) and 20-40 years (15.09%), while only 4(0.90%) patients were aged >80 years. A statistically significant association with severity of retinopathy and the age of the patients was observed. Proportion of Group I (No retinopathy) was higher in younger patients i.e. 20- 40 (74.6%) and 41-60 (54.3%) as compared to elderly cases i.e. 61-80 (46.2%) and this difference was found to be statistically significant (p<0.001). Statistically significant association was found between the severity of retinopathy and duration of diabetes (p<0.001). Proportion of severe to very severe retinopathy and proliferative diabetic retinopathy were higher in higher grade of microalbuminuria (Grade II and Grade III). A statistically significant association between microalbuminuria grade and severity of retinopathy was observed (p<0.001). Total cholesterol was found to be high (240 mg/dl) in 13.74%patients. Prevalence of retinopathy was 60.7%, in patients having high total cholesterol levels. Proportional difference in severity of retinopathy in patients with different total cholesterol levels was found to be statistically significant (p=0.002). Trivariate analysis between severity of retinopathy, microalbuminuria and serum cholesterol levels, revealed that in microalbuminuria grade 0, difference in prevalence of retinopathy in patients with different serum cholesterol levels was not found to be statistically significant. CONCLUSION: Duration of diabetes and microalbuminuria have been found to be the independent risk factors for diabetic retinopathy, but serum cholesterol levels did not show an independent role in our study. The findings in present study endorsed the view that microalbuminuria poses a risk for diabetic retinopathy which is affected by duration of diabetes, level of glycemic control and lipid levels.
, Hanaa A. Mohammad, Ebtsam F. Mohamed, Ahmed G. Askar
Egyptian Pediatric Association Gazette, Volume 66, pp 85-90; doi:10.1016/j.epag.2018.10.003

Abstract:
Type 1 diabetes mellitus (T1DM) carries a long-term burden of increased microvascular complications in the form of nephropathy, retinopathy, and neuropathy. As the incidence of T1DM continues to rise, the burden of microvascular complications will also increase and negatively influence the prognosis of young patients. Microalbuminuria (MA) represents the earliest clinical indication of diabetic nephropathy and is a predictor of increased cardiovascular morbidity and mortality. Our study’s aim was to determine the prevalence of microvascular complications among type 1 diabetic patients in Assiut University Children Hospital, Upper Egypt and to find out its correlation with various risk factors. The study was cross-sectional one carried on a sample of 180 type 1 diabetic children and adolescents aged from 6 to 21 years. Patients were subjected to full history taking, physical examination, and investigations of HbA1c, lipid profile, early morning spot urine albumin/creatinine ratio as well as fundus examination. The prevalence of microalbuminuria was 20.5%, macroalbuminuria was 7.8%, diabetic retinopathy was 1.1%, and diabetic neuropathy was 5.5%. Patients with microvascular complications had a significantly higher frequency of DKA (39.2% vs. 10.6%, p = 0.000) and hypoglycemic attacks (47.1% vs. 29.5%, p = 0.001) than those without microvascular complications. Furthermore, studied patients with microvascular complications had significantly higher mean ± SD HbA1c (9.99 ± 1.61 vs. 8.51 ± 1.5, p = 0.000) and serum cholesterol (174.98 ± 48.12 vs. 166.26 ± 43.28, p = 0.05) in comparison to patients without microvascular complications. The prevalence rate of microvascular complications was considerably high among diabetic patients in Assiut governorate, Egypt especially with poor glycemic control and dyslipidemia. Regular screening for microvascular complications is recommended for all diabetic patients, as early treatment is critical for reducing cardiovascular risks and slowing the progression to late stages of diabetic nephropathy.
Tania Nasreen, Sheuly Ferdousi, Khorshed Alam, Tuhin Sultana, Tashmim Farhana Dipta, Shahjada Selim
Northern International Medical College Journal, Volume 9, pp 291-294; doi:10.3329/nimcj.v9i2.38909

Abstract:
Background : Magnesium (Mg++) deficiency is associated with poor glycemic control and Mg++ supplementation lowers blood sugar, improves insulin sensitivity and delays diabetic complications such as diabetic nephropathy, diabetic neuropathy, diabetic retinopathy. Objective : This study was designed to know the status of serum Mg++ in type 2 diabetic subjects with microalbuminuria and normoalbuminuria.Methodology : This study was conducted at the Department of Laboratory Medicine (Clinical Pathology) in collaboration with BIRDEM General Hospital, Dhaka. In this study, serum magnesium level and urine microalbumin level of 120 newly detected type 2 diabetic patients were measured. Both levels were measured by biochemical auto analyzer (Siemens Dimension RL Max).Result : The mean microalbumin level was found 22.9±3.1 mg/L with range from 2-105 mg/L and the mean magnesium level was found 1.9±0.3 mg/dl with range from 1.5-2.4 mg/dl. Pearson’s correlation coefficient was -0.353 between serum magnesium level and urine microalbumin which was statistically significant (p value < 0.05). Therefore, there was a linear negative correlation between serum magnesium level and urine microalbumin.Conclusion : The present study revealed negative correlation between serum magnesium level and urine microalbumin.Northern International Medical College Journal Vol.9(2) Jan 2018: 291-294
Published: 24 October 2018
Advances in Nephropathy; doi:10.5772/intechopen.79331

Abstract:
Diabetic nephropathy is the commonest microvascular complication in both types 1 and 2 diabetes mellitus. Disease pathogenesis is based on a multifactorial interaction between metabolic and hemodynamic factors. In response to hyperglycemia, which disrupts the body’s metabolic milieu, a cascade of complex molecular events occur leading to glomerular hypertrophy, tubular inflammation, mesangial expansion, oxidative stress, and renal fibrosis. Beyond the conventional microalbuminuria, which can predict disease onset, novel biomarkers are now proving more reliable as predictive tools. While several reports show that glomerular and tubular biomarkers are more sensitive than microalbuminuria, tubular markers specifically constitute earlier predictors of the disease. Similarly, biomarkers of inflammation and oxidative stress have been demonstrated as dependable diagnostic tools. As an important cause of mortality from end-stage renal disease (ESRD), diabetic nephropathy constitutes an important challenge in diabetic care. Interestingly, strict glycemic control assessed by glycated hemoglobin (Hb A1 c) estimates, and antihypertensive therapy with angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB) ± calcium-channel blockers form the main strategies for preventing its onset and slowing down its progression. Other strategies include uric acid antagonist, and renin and endothelin inhibitors. This book chapter discusses these predictive tools and possible preventive strategies.
Yingli Jia, Jinzhao He, Liang Wang, Limin Su, Lei Lei, Wei Huang, Xiaoqiang Geng, Shun Zhang, Xiaolu Meng, Hong Zhou, et al.
Published: 23 February 2018
Cellular Physiology and Biochemistry, Volume 45, pp 1747-1758; doi:10.1159/000487783

Abstract:
Background/Aims: A sodium-glucose co-transporter-2 inhibitor dapagliflozin is widely used for lowering blood glucose and its usage is limited in type 2 diabetes mellitus patients with moderate renal impairment. As its effect on kidney function is discrepant and complicated, the aim of this study is to determine the effect of dapagliflozin on the progression of diabetic nephropathy and related mechanisms. Methods: Twelve-week-old male C57BL/6 wild-type and db/db mice were treated with vehicle or 1 mg/kg dapagliflozin for 12 weeks. Body weight, blood glucose, insulin tolerance, glucose tolerance, pyruvate tolerance and 24-hour urine were measured every 4 weeks. At 24 weeks of age, renal function was evaluated by blood urea nitrogen level, creatinine clearance, urine output, urinary albumin excretion, Periodic Acid-Schiff staining, Masson’s trichrome staining and electron microscopy. Changes in insulin signaling and gluconeogenic key regulatory enzymes were detected using Western blot analysis. Results: Dapagliflozin did not alleviate but instead aggravated diabetic nephropathy manifesting as increased levels of microalbuminuria, blood urea nitrogen, and glomerular and tubular damage in db/db mice. Despite adequate glycemic control by dapagliflozin, urinary glucose excretion increased after administration before 24 weeks of age and was likely associated with renal impairment. Increased urinary glucose excretion was mainly derived from the disturbance of glucose homeostasis with elevated hepatic and renal gluconeogenesis induced by dapagliflozin. Although it had no effect on insulin sensitivity and glucose tolerance, dapagliflozin further induced the expression of gluconeogenic key rate-limiting enzymes through increasing the expression levels of FoxO1 in the kidney and liver. Conclusion: These experimental results indicate that dapagliflozin aggravates diabetes mellitus-induced kidney injury, mostly through increasing gluconeogenesis.
, Smriti Misra, Swati Yadav,
International Journal of Ophthalmic Research, Volume 4, pp 282-286; doi:10.17554/j.issn.2409-5680.2018.04.79

The publisher has not yet granted permission to display this abstract.
, Tomoko Suzuki, Seigo Sugiyama, Noboru Kurinami, Akira Yoshida, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi, Hideaki Jinnouchi
Journal of Clinical Medicine Research, Volume 10, pp 478-485; doi:10.14740/jocmr3400w

Abstract:
Background: Smoking cessation in newly diagnosed type 2 diabetes patients is reported to be associated with amelioration of metabolic parameters and blood pressure (BP), and the reduction of microalbuminuria. The aim of this study is to demonstrate changes in BP, pulse rate (PR), and microalbuminuria in already diagnosed diabetes patients who quit smoking.Methods: We retrospectively evaluated diabetes outpatients who were habitual smokers, and who visited to our smoking cessation clinic. Patients were divided into two groups based on their smoking status at the termination of a 3-month smoking cessation program (smoking cessation group and smoking group), and analyzed systolic and diastolic BPs, PR, HbA1c, and body weight at the start date, and at 1, 3, 6, and 12 months thereafter. The urinary albumin-to-creatinine ratio was also measured at the start date and at 12 months.Results: Thirty-five patients met our criteria. Mean diabetes duration was 12 years. Eighteen patients (52%) quit smoking. Success or failure of smoking cessation depended on nicotine dependence rather than good or bad glycemic control. Both BP and PR decreased significantly after 1 month or later in the smoking cessation group without worsening HbA1c, while both parameters did not show any changes in the smoking group. Microalbuminuria was also ameliorated significantly at 12 months compared with that at the start date in the smoking cessation group (95.8 ± 92.9 mg/gCr vs. 75.5 ± 96.3 mg/gCr, P = 0.0059), while it did not show a significant change in the smoking group. (61.9 ± 43.5 mg/gCr vs. 97.7 ± 90.4 mg/gCr, P = 0.1039).Conclusions: Smoking cessation might cause a reduction in chronic kidney disease progression through ameliorating microalbuminuria without metabolic adverse effects in patients already diagnosed with diabetes mellitus.J Clin Med Res. 2018;10(6):478-485doi: https://doi.org/10.14740/jocmr3400w
Hardeep Singh Dua, Manan Anand
International Journal of Advances in Medicine, Volume 4; doi:10.18203/2349-3933.ijam20175120

Abstract:
Background: Diabetes is a common and serious disease leading to chronic, mostly irreversible macro and microvascular complications.Methods: 50 Patients, attending Diabetic OPD at SGRD hospital, Amritsar. Asymptomatic patients with no symptoms or history of IHD and normal ECG with microalbuminuria were enrolled in the study. A complete clinical examination was done.Results: The prevalence of microalbuminuria increased with worsening glycemic control, as evidenced by prevalence of 74 % in patients with HbA1c of more than 9 percent. The prevalence of microalbuminuria increased with the duration of diabetes, as evidenced by prevalence in 48 % in patients, with duration of diabetes of more than 11 years. The prevalence of microalbuminuria increased with increased in BMI, as evidenced by prevalence of 56 % in overweight Patients. The prevalence of microalbuminuria increased in patients of Diabetic Retinopathy, as evidenced by prevalence of 82 % in patients of Diabetic Retinopathy. In the present study, 70.8 % patients with duration of diabetes in the range 11-15 years had positive treadmill test.Conclusions: Hence, in this study it was observed that longer the duration of diabetes with microalbuminuria, greater is the predisposition for silent myocardial ischemia. In the present study, 64 % of asymptomatic patients with microalbuminuria had a positive treadmill exercise test. Hence, we deduce from this study that microalbuminuria is an independent risk factor for silent myocardial ischemia.
, Nikhil Gupta, Ronnie Aronson
Diabetes Technology & Therapeutics, Volume 19, pp 685-691; doi:10.1089/dia.2017.0134

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L. L. Bolotskaya, E. G. Bessmertnaya, М. В. Шестакова, M. Sh. Shamkhalova, Л. В. Никанкина, A. V. Ilyin, I S Glek, A. V. Zolotukhin, И. И. Дедов
Terapevticheskii arkhiv, Volume 89, pp 17-21; doi:10.17116/terarkh2017891017-21

Abstract:
Aim. To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). Subjects and methods. A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. Results. During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. Conclusion. The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.
BMC Endocrine Disorders, Volume 17; doi:10.1186/s12902-017-0212-4

Abstract:
Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control. IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency. Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%). The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.
Diabetes Therapy, Volume 8, pp 1215-1226; doi:10.1007/s13300-017-0302-3

Abstract:
Diabetes is the leading cause of chronic kidney disease, and even in the absence of albuminuria, decreased renal function in type 2 diabetes mellitus (T2DM) patients increases the risk for major adverse cardiovascular events and death. The evidence derived from recent studies suggests that intensive glucose control not only reduces the risk for microalbuminuria and macroalbuminuria but may also decrease the rate of decline of glomerular filtration rate (GFR). Although insulin therapy is widely used in patients with T2DM and renal disease, metabolic control is particularly difficult to achieve and manage because of the limited therapeutic options and the frequent comorbidities seen in this population. Recent evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors may offer a better choice for improving glycemic control in T2DM patients with low GFR. This review will focus on vildagliptin, a DPP-4 inhibitor with a large body of evidence in patients with moderate to severe renal failure and a good clinical profile in terms of efficacy and safety. In particular, vildagliptin, with appropriate dose adjustment, provides clinically important reductions in glycated hemoglobin, without increasing weight and the risk of hypoglycemia even in patients with severe chronic kidney disease.
The American Journal of Cardiology, Volume 120; doi:10.1016/j.amjcard.2017.05.010

Abstract:
For many years, it was widely accepted that control of plasma lipids and blood pressure could lower macrovascular risk in patients with type 2 diabetes mellitus (T2DM), whereas the benefits of lowering plasma glucose were largely limited to improvements in microvascular complications. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA-REG OUTCOME) study demonstrated for the first time that a glucose-lowering agent, the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, could reduce major adverse cardiovascular events, cardiovascular mortality, hospitalization for heart failure, and overall mortality when given in addition to standard care in patients with T2DM at high cardiovascular risk. These results were entirely unexpected and have led to much speculation regarding the potential mechanisms underlying cardiovascular benefits. In this review, the results of EMPA-REG OUTCOME are summarized and put into perspective for the endocrinologist who is treating patients with T2DM and cardiovascular disease. Macrovascular disease remains the leading cause of death in people with type 2 diabetes mellitus (T2DM). Thus, it is somewhat surprising that major landmark trials using glucose-lowering interventions in people with T2DM have failed to demonstrate any macrovascular benefits at the end of the intervention period, even when stringent glycemic control was achieved.1,2,3,4 In addition, the contention that some glucose-lowering interventions (eg, rosiglitazone) might actually increase the risk of cardiovascular events and death was worrisome.5 Pursuant to the latter, in 2008, the US Food and Drug Administration (FDA) mandated cardiovascular safety studies for all new glucose-lowering therapies.6 Subsequently, results from many cardiovascular outcome trials have been published.7,8,9,10,11 For dipeptidyl peptidase-4 inhibitor cardiovascular outcome trials, there was an unexpected increase in the risk of hospitalization for heart failure in patients receiving saxagliptin versus those on placebo in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.07-1.51; P = .007),10 although no statistically significant differences in this end point were noted for alogliptin versus placebo in a post hoc analysis of the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study (HR, 1.07; 95% CI, 0.79-1.46; P = .657)12 or for sitagliptin in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) primary analysis (HR, 1.00; 95% CI, 0.83-1.20; P = .98).7The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA-REG OUTCOME), the cardiovascular outcome trial investigating the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, was the first clinical study of a glucose-lowering agent to demonstrate superiority for the primary end point and boasted a particularly robust reduction in the risk of cardiovascular death in patients with T2DM and established cardiovascular disease.13 Although the major action of SGLT2 inhibitors is to target the kidney to reduce the reabsorption of glucose and promote urinary glucose excretion (reviewed in the articles by Thrasher14 and Wanner15), the surprising results of EMPA-REG OUTCOME have generated numerous postulated mechanisms of action for the observed reduction in cardiovascular disease risk in patients with T2DM (reviewed in the article by Staels16 in this Supplement).Summary of EMPA-REG OUTCOME ResultsJump to SectionSummary of EMPA-REG OUTCOME ResultsMultiple Risk Factor Reduction with EmpagliflozinPotential Mechanisms Involved in Cardiorenal Benefits of EmpagliflozinImplications for Clinical PracticeConclusionsReferencesIt is important to first point out that EMPA-REG OUTCOME was not designed to assess the glucose-lowering effects of empagliflozin or how glucose-lowering affects cardiovascular outcomes. Instead, EMPA-REG OUTCOME was designed to assess the cardiovascular safety of empagliflozin. Nevertheless, the study design did prespecify that it would test the superiority of empagliflozin over placebo for cardiovascular protection if noninferiority was achieved. The results demonstrated a reduction in major adverse cardiovascular events (MACE), cardiovascular mortality, and hospitalization for heart failure in patients with T2DM and preexisting cardiovascular disease who received empagliflozin in addition to standard care13 when tested for both noninferiority and superiority. The trial continued until a primary outcome event had occurred in at least 691 patients; the median duration of treatment was 2.6 years, and the median observation time was 3.1 years. The EMPA-REG OUTCOME population had a mean age of 63 years and long-standing diabetes (>10 years in 57% of patients), and more than 99% of patients had established cardiovascular disease (76% had coronary artery disease; 47% had a history of myocardial infarction). The primary end point occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group (10 mg and 25 mg doses) and in 282 of 2333 patients (12.1%) in the placebo group, resulting in a 14% relative risk reduction for the primary composite 3-point MACE outcome of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke in patients receiving empagliflozin compared with those receiving placebo (HR, 0.86; 95.02% CI, 0.74-0.99; P <.001 for noninferiority). With no significant decrease in the relative risk of stroke or myocardial infarction, the MACE risk reduction was primarily driven by a 38% relative risk reduction in cardiovascular death (HR, 0.62; 95% CI, 0.49-0.77; P <.001). In addition, there was a 32% relative risk reduction in all-cause mortality (HR, 0.68; 95% CI, 0.57-0.82; P <.001) and a 35% relative risk reduction in the incidence of hospitalization for heart failure (HR, 0.65; 95% CI, 0.50-0.85; P = .002). An analysis of secondary microvascular outcomes demonstrated that patients on empagliflozin experienced slower progression of kidney disease and a lower risk of progressing to macroalbuminuria than those on placebo17 (this is discussed in the article by Wanner15).Multiple Risk Factor Reduction with EmpagliflozinJump to SectionSummary of EMPA-REG OUTCOME ResultsMultiple Risk Factor Reduction with EmpagliflozinPotential Mechanisms Involved in Cardiorenal Benefits of EmpagliflozinImplications for Clinical PracticeConclusionsReferencesGiven the beneficial effects of empagliflozin on glycated hemoglobin (HbA1c), blood pressure, and body weight, it is intuitive to liken EMPA-REG OUTCOME to a traditional multiple risk factor intervention trial.18 For example, HbA1c was reduced by 0.45%, blood pressure was reduced by approximately 5/2 mm Hg, and body weight was reduced by approximately 2% in the active treatment group.19 Nevertheless, the difference in the primary outcome became evident approximately 3 months after starting empagliflozin,20 making it highly unlikely that the mechanism is related to glucose-lowering or antiatherosclerotic effects. For example, statin trials have demonstrated reduction in cardiovascular events in patients with T2DM after significant time exposure to the drugs (ie, 1-2 years), with generally more pronounced effects on cardiovascular events than on cardiovascular mortality.21,22 Specifically, statins have been shown to reduce myocardial infarction and stroke by approximately 20%, whereas the effect on cardiovascular death and all-cause mortality is more limited (–13% and –9%, respectively, per mmol/L low-density lipoprotein cholesterol reduction).22 Even when a formal multifactorial intervention is undertaken, such as in the Intensified Multifactorial Intervention in Patients With Type 2 Diabetes and Microalbuminuria (STENO-2) trial (ie, renin-angiotensin system blockers, aspirin, and lipid-lowering agents), cardiovascular protection is not observed for several years.23 Last, although the glucagon-like peptide-1 agonist, liraglutide, has been shown to lower 3-point MACE (in addition to lowering HbA1c and body weight),8 its impact on cardiovascular outcomes did not become apparent until 12 to 18 months of treatment. Collectively, the short time course for risk reduction in cardiovascular outcomes seen in EMPA-REG OUTCOME has generated as much discussion as the major results themselves.The early separation of the Kaplan-Meier survival curves for cardiovascular death in EMPA-REG OUTCOME resembles results observed in heart failure studies, which showed separation of survival curves within 3 to 6 months of starting treatment with a β-blocker.24,25 In addition, eplerenone (a diuretic selectively targeting aldosterone receptors) significantly reduced the risk of the composite end point of cardiovascular mortality and cardiovascular hospitalization by 17% in a subgroup of patients with T2DM and congestive heart failure; this effect was reported within months of beginning study treatment.26 Given that only 10% of participants (706/7020) in EMPA-REG OUTCOME had known heart failure on enrollment, the 35% reduction in hospitalization for heart failure may represent prevention of new-onset heart failure or prevention of an exacerbation of existing, potentially undiagnosed heart failure in this population.27,28 Indeed, the effect of empagliflozin on cardiac hemodynamics is an area of intense scientific investigation.29Finally, the results of EMPA-REG OUTCOME become even more impressive when we consider that they occurred in addition to a background of near-optimal treatment of blood pressure, plasma lipids, and coagulation status. For example, 95% of patients received antihypertensive therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 81%; β-blockers, 6
Jai P Yogi, Anita Semar
Journal of Mahatma Gandhi University of Medical Sciences and Technology, Volume 2, pp 1-6; doi:10.5005/jp-journals-10057-0021

The publisher has not yet granted permission to display this abstract.
Cong Ma, Junqin Sheng, ,
Scientific Reports, Volume 7; doi:10.1038/srep44291

Abstract:
1,5-anhydroglucitol (1,5-AG), uric acid and urinary proteins are excreted into the urine with increasing glucosuria. In the present retrospective study we analyzed whether these factors could be used as indicators for type 2 diabetes mellitus (T2DM) glucose control in 6,766 (T2DM) patients. There were 3,988 cases (58.9%) with HbA1c ≤ 6.5%, 853 cases (12.61%) with HbA1c levels ranging from 6.5% to 7% and 1,925 cases (28.5%) with HbA1c > 7%. HbA1c percentages were correlated with age, MA and 1,5-AG serum concentrations (P < 0.001). The serum uric acid concentration (P < 0.001) was significantly lower in elevated MA (P < 0.001) and 24-hour urinary protein (P = 0.024) patients. Hb1Ac percentages (P < 0.001) were significantly enhanced in patients with 1,5-AG serum concentrations ≤10 mg/L compared to >10 mg/L. With a derived receiver operating characteristic (ROC) curve, a 1,5-AG cut-off value of 11.55 mg/L for hyperglycemia could be diagnosed with a specificity of 71.2 (69.7–72.6) and a sensitivity of 75.3 (73.6–76.9). The serum 1,5-AG concentration is a marker for hyperglycemia and may be particularly useful as an indicator for short-term glycemic excursions in order to improve treatments in T2DM patients.
Sigal Singer, Nurit Pilpel, Orit Pinhas‐Hamiel
Published: 17 January 2017
by Wiley
Pediatric Diabetes, Volume 18, pp 803-807; doi:10.1111/pedi.12488

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, Gil Leibowitz, Deepak L. Bhatt, , , Cheryl Wei, KyungAh Im, Aliza Rozenberg, Ilan Yanuv, Christina Stahre, et al.
Published: 17 October 2016
Diabetes Care, Volume 40, pp 69-76; doi:10.2337/dc16-0621

Abstract:
OBJECTIVE Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESULTS At baseline, 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio [ACR] 300 mg/g). Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) (P = 0.021, P < 0.001, and P = 0.049 for individuals with baseline normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). At 2 years, the difference in mean ACR change between saxagliptin and placebo arms was −19.3 mg/g (P = 0.033) for estimated glomerular filtration rate (eGFR) >50 mL/min/body surface area per 1.73 m2 (BSA), −105 mg/g (P = 0.011) for 50 ≥ eGFR ≥ 30 mL/min/BSA, and −245.2 mg/g (P = 0.086) for eGFR 6.0 mg/dL, were similar as well. CONCLUSIONS Treatment with saxagliptin improved ACR, even in the normoalbuminuric range, without affecting eGFR. The beneficial effect of saxagliptin on albuminuria could not be explained by its effect on glycemic control.
Amiroh Kurniati, Tahono Tahono
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY, Volume 21, pp 250-256; doi:10.24293/ijcpml.v21i3.736

Abstract:
Diabetes Mellitus (DM) type 2 is a metabolic disease that prevalence increasing. A chronic hyperglycemia with poor glycemic control can stimulate oxidative stress, which will continue to occurrence of complications in the kidneys characterized by the presenceof microalbuminuria can be measured by the ratio of urinary albumin creatinine ratio (UACR) and the change in estimated glomerular filtration rate (eGFR). The aims of this study was to know the correlation between the UACR with HbA1c value and eGFR in patients with type 2 DM by finding them out. This study used cross sectional research design. Subjects were patients with type 2 DM who attend control in Endocrinology Subdivision of Internal Medicine Departement and perform blood and urine tests in Clinical Pathology Laboratory in Dr. Moewardi Hospital Surakarta in August 2013. To determine the pattern of the data distribution, the researchers used KolmogorovSmirnov test, and to analyse the result used Spearman (r) correlation with p
John I. Anetor, Chukwuemelie Z. Uche, Emmanuel B. Ayita, Solomon K. Adedapo, Jokotade O. Adeleye, Gloria O. Anetor, Sola K. Akinlade
Frontiers in Public Health, Volume 4; doi:10.3389/fpubh.2016.00114

Abstract:
Cadmium (Cd) has recently emerged as a major concern not only in environmental toxicology but also in metabolic diseases such as diabetes mellitus (DM) and its complications. Conflicting data aside, these studies have not been examined in a clinical population undergoing management as well as possible modulation by the prominent metabolic antagonist of Cd such as zinc (Zn). This study examined the relationship between cadmium levels, glycemic control and renal pathology in established type II diabetic patients with focus on populations exposed to modern environmental health hazards (MEHHs). Sixty-five participants, consisting of 45 type-2 diabetics and 20 non-diabetics were enrolled for the study, mean age 61.51 ± 5.27 years. Glycated haemoglobin (HbA1C) was used to classify them into three sub-groups; (A) good glycemic control (44.4%), (B) fair glycemic control (24.4%) and (C) poor glycemic control (31.1%). Plasma levels of glucose, Cd, Zn, HbA1C, creatinine, urinary creatinine, microalbuminuria and estimated glomerular filtration rate (e-GFR) were determined in all participants using standard methods. Fasting plasma glucose (FPG), was higher in diabetics than in non-diabetics (p= 0.000) as well as Zn level, though not significantly. Interestingly, Cd Level, Cd/Zn ratio and Urinary creatinine were significantly lower in diabetics than in non-diabetics. The group with poor glycemic control (C) had significantly higher Cd level compared to the one with good glycemic control (group A). The renal function revealed that microalbuminuria and Urinary albumin/creatinine ratio (UACR) was significantly higher in diabetics than in non-diabetics while e-GFR was found to be similar in both diabetics and non-diabetics. UACR inversely correlated with Cd level, while Plasma creatinine level positively correlated to Cd but not significantly. Correlation between Cd and HbA1C revealed non-significant inverse correlation (r = -0.007; p> 0.05), while Zn showed a significant inverse correlation with Cd (r= - 0.317; p<0.014). The lower Cd level in diabetics compared to non-diabetics probably reflects the modulating effect of Zn in treated diabetics given nutritional education in addition to their regular regime including good sources of Zn. The renal insufficiency with increasing Cd level may suggest that the progression of renal impairment may not be responsive to the
Mohamed Abo El-Asrar, , Eman Abdel Rahman Ismail, Alshaimaa Abo Bakr
Angiogenesis, Volume 19, pp 421-431; doi:10.1007/s10456-016-9517-6

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Pankaj Kumar Saini, Manoj Saluja, Shyam Bihari Meena
Current Medicine Research and Practice, Volume 6, pp 113-116; doi:10.1016/j.cmrp.2016.05.002

Bedowra Zabeen, Maria E. Craig, Sohaib A. Virk, Alison Pryke, Albert K. F. Chan, Yoon Hi Cho, Paul Z. Benitez-Aguirre, Stephen Hing,
Published: 6 April 2016
PLOS ONE, Volume 11; doi:10.1371/journal.pone.0153033

Abstract:
To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). Prospective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes. In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES.
, Julia Stingl, Albrecht Dapp, Michael D. Denkinger, Peter Fasching, Peter M. Jehle, Sigrun Merger, Steffen Mühldorfer, Urte Pieper, Andreas Schuler, et al.
Diabetes Research and Clinical Practice, Volume 112, pp 73-81; doi:10.1016/j.diabres.2015.10.026

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, Sunita Neupane, , Krishna Kumar Agrawal, Archana Jayan, Sujata Shrestha, Amit Chandra Jha
Published: 1 January 2016
Nigerian Medical Journal, Volume 57, pp 119-123; doi:10.4103/0300-1652.182074

Abstract:
Diabetes mellitus (DM) is a chronic disease characterized by insulin deficiency or peripheral resistance resulting in hyperglycemia. Poor glycemic control leads to diabetic complications. Hyperuricemia has been reported with increased risk of renal insufficiency. The aim of this study was to evaluate the relationship between serum uric acid concentration, degree of urinary albumin excretion (UAE) and glycated hemoglobin (HbA1c) in Type 2 DM (T2DM) patients. Serum uric acid concentrations, urine microalbumin, and HbA1c were measured in fifty T2DM patients. We then evaluated relationship between uric acid concentrations, degree of UAE and glycemic control as well as other confounding variables. Serum uric acid concentration correlated positively with UAE (r = 0.323, P < 0.05), age (r = 0.337, P < 0.05), age at onset (r = 0.341, P < 0.05), and duration of DM (r = 0.312, P < 0.05). Multiple regression analysis demonstrated that serum uric acid concentration (β = 0.293, P < 0.0001), duration of DM (β = 0.261, P < 0.0001), HbA1c (β = 0.173, P < 0.005), and systolic blood pressure (β = 0.268, P < 0.005) were independent determinants of UAE. Serum uric acid concentration is associated with microalbuminuria and HbA1c in T2DM patients.
Heba M.T. Elweshahi, Azza A Esmail, Dalia Abd Elmotey
Egyptian Journal of Obesity, Diabetes and Endocrinology, Volume 2; doi:10.4103/2356-8062.184397

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K Srjana, P Amith Kumar
Published: 1 January 2016
MRIMS Journal of Health Sciences, Volume 4; doi:10.4103/2321-7006.302278

The publisher has not yet granted permission to display this abstract.
, Anthony Sherman, Mary Joan Monari-Sparks, Olga Schweiker, Navjot Jain, Etty Sims, Michelle Breda, Gita P Byraiah, Ryan George Belecanech, Michael Domenic Coletta, et al.
North American Journal of Medical Sciences, Volume 8, pp 31-39; doi:10.4103/1947-2714.175197

Abstract:
Type 2 diabetes mellitus (T2DM) is a poorly controlled epidemic worldwide that demands active research into mitigation of the factors that are associated with poor control. The study was to determine the factors associated with suboptimal glycemic control. Electronic medical records of 263 adult patients with T2DM in our suburban internal medicine office were reviewed. Patients were divided into two groups: Group 1 [optimal diabetes control with glycosylated hemoglobin (HbA1c) of 7% or less] and Group 2 (suboptimal diabetes control with HbA1c greater than 7%). The influence of factors such as age, gender, race, social history, comorbid conditions, gestational diabetes, family history of diabetes, diabetes management, statin use, aspirin use, angiotensin convertase enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) use, body mass index (BMI), blood pressures, lipid profile, and urine microalbumin level were analyzed in the two groups. In the suboptimal diabetes control group (N = 119), the majority (86.6%) of the patients were 41-80 years old. Factors associated with the suboptimal control were male gender [odds ratio (OR) 2.6, 95% confidence interval (CI), 1.579-4.321], Asian ethnicity (OR 1.4, 95% CI, 0.683-3.008), history of peripheral arterial disease (PAD; OR 3.9, 95% CI, 1.017-14.543), history of congestive heart failure (CHF; OR 3.9, 95% CI, 1.017-14.543), elevated triglycerides (OR 1.004, 95% CI, 1.000-1.007), and elevated urine microalbumin level of 30 mg/24 h or above (OR 4.5, 95% CI, 2.446-8.380). Patients with suboptimal diabetes control had a 3.8 times greater odds (95% CI, 1.493-6.885) of receiving the insulin and oral hypoglycemic agent together. In adult patients with T2DM, male gender, Asian ethnicity, CHF, PAD, management with insulin along with oral hypoglycemic agents, hypertriglyceridemia, and microalbuminuria were associated with suboptimal control.
, Alessandro Rizzi, Giovanna Petrucci, Flavia Ciaffardini, Luigi Tanese, Francesca Pagliaccia, Viviana Cavalca, Angela Ciminello, , , et al.
Published: 15 October 2015
Diabetes, Volume 65, pp 503-509; doi:10.2337/db15-0936

Abstract:
Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.
, Hongying Dai, Stephen A. Delurgio, David D. Williams, Marcus Lind, Susana R. Patton, John A. Spertus, Mikhail Kosiborod, Mark A. Clements
Published: 17 September 2015
by Wiley
Pediatric Diabetes, Volume 17, pp 398-406; doi:10.1111/pedi.12300

Abstract:
To test the hypothesis that HbA1c variability, as measured by standard deviation (SD), is associated with increased risk for incident microalbuminuria and persistent microalbuminuria in pediatric type 1 diabetes (T1D). A retrospective analysis using data from electronic health records was performed on 1195 patients from a pediatric diabetes clinic network in the Midwest USA from 1993 to 2009 with ≥1 yr of T1D, ≥4 total HbA1c values, ≥2 HbA1c values/yr, ≥1 urine microalbumin. Microalbuminuria, the main outcome was defined as albumin excretion rate ≥20 mcg/min or 2 of 3 consecutive urine microalbumin/creatinine ≥30 mg/gm. Patients who had persistently high microalbumin or who were treated with an angiotensin-converting-enzyme inhibitor within 1 yr were considered to have persistent microalbuminuria. Sex, race, age, diagnosis age, and duration were covariates. Median numbers of per-patient HbA1c and microalbumin results were 14 and 3, respectively. Median intrapersonal mean HbA1c and SD were 8.62% (70.72 mol/mol) and 1.47% (16.07 mmol/mol), respectively. The median interquartile range (IQR) of diagnosis age was 9.4 yr (6.26-12.02) and diabetes duration was 4.97 yr (2.93-7.64). A total of 172 patients (14.4%) developed microalbuminuria; 55 (4.6%) had persistent microalbuminuria. Patients with higher SD of HbA1c had shorter time to microalbuminuria. In time-dependent Cox Proportional Hazard models, updated SD of HbA1c was significantly associated with microalbuminuria [univariate hazard ratio (HR) 1.48 (1.25-1.76); multivariable HR 1.28 (1.04-1.58)], whereas updated mean HbA1c was not [univariate HR 1.08 (0.97-1.22); multivariable HR 1.05 (0.92-1.2)]. Patients with persistent microalbuminuria had similar HRs. HbA1c variability is independently associated with development of microalbuminuria in children with T1D, highlighting the importance of maintaining stable glycemic control in pediatric patients.
Diabetology & Metabolic Syndrome, Volume 7, pp 1-9; doi:10.1186/s13098-015-0062-z

Abstract:
Vildagliptin, a DPP-4 inhibitor widely used for the treatment of type 2 diabetes mellitus (T2DM), shows beneficial effects on endothelial function. This study aims to evaluate the effect of vildagliptin on endothelial function and arterial stiffness in patients with T2DM and hypertension. Fifty over 35-year-old patients with T2DM and hypertension, without cardiovascular disease, will be randomly allocated to two groups: group 1 will receive vildagliptin added-on to metformin and group 2, glibenclamide added-on to metformin. Biochemical tests (glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, alanine aminotransferase, ultrasensitive C-reactive protein, and microalbuminuria), 24-h non-invasive ambulatory blood pressure monitoring, and assessment of endothelial function and arterial stiffness will be performed in both groups before and after 12 weeks of treatment. The endothelial function will be assessed by peripheral arterial tonometry, which measures the reactive hyperemia index (vasodilation), and arterial stiffness will be evaluated by applanation tonometry. All analysis will be performed using SPSS Statistical Software. For all analysis, a 2-sided P < 0.05 will be considered statistically significant. The study started in December 2013 and patient recruitment is programed until October 2015. The expected results are that vildagliptin will improve the endothelial function in patients with T2DM and hypertension compared to glibenclamide treatment, independently of glycemic control. It is expected that this DPP-4 inhibitor will improve endothelial function in patients with T2 DM. Trial registration: Clinical Trials NCT02145611, registered on 11 Jun 2013
S Sushma, Ms Kusuma Devi, S Naveen, Edwin Devadoss
Journal of Health Sciences & Research, Volume 6, pp 1-4; doi:10.5005/jp-journals-10042-1008

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Suma K R, Srinath S, Ganesh Shetty
Journal of Evolution of Medical and Dental Sciences, Volume 4, pp 6429-6434; doi:10.14260/jemds/2015/934

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