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Taqwaa Sueud, Najah R. Hadi, Raed Abdulameer, Dina A. Jamil, Hayder A. Al-Aubaidy
Diabetes & Metabolic Syndrome: Clinical Research & Reviews, Volume 13, pp 564-568; doi:10.1016/j.dsx.2018.11.022

The publisher has not yet granted permission to display this abstract.
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

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, Ritika Mullick
International Journal of Ophthalmic Research, Volume 5, pp 308-313; doi:10.17554/j.issn.2409-5680.2019.05.87

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
Eman B. KamalEldeen , 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

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

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
Abdulbari Bener , Mustafa Eliaçık, Hakan Cincik, Mustafa Öztürk, Ralph A. DeFronzo, Muhammad Abdul-Ghani
BioMed Research International, Volume 2018, pp 1-8; doi:10.1155/2018/2714590

The current study was aiming to investigate the relation between vitamin D, retinopathy, and hearing loss among type 2 diabetes mellitus (T2DM) patients. Cross-sectional study carried on 638 subjects aged between 20 and 60 years who visited the Endocrinology, Ophthalmology, and ENT Outpatient Clinics of the Medipol Hospital during the period from March 2016 to May 2017. Two audiometers Grason Stadler GSI 61 and Interacoustics AC40 Clinical audiometer were used to evaluate the hearing loss. Risk factors for diabetic retinopathy were evaluated, including age, sex, diabetes duration, glycated hemoglobin (HbA1c), hypertension, and lipid profiles. The mean age (± SD, in years) for retinopathy with hearing loss versus normal subjects was 47.7 ±10.2 versus 48.5±9.1. The associated risk factors were significantly higher in T2DM with hearing loss, hypertension (32.6% versus 15.7%), tinnitus (40.0% versus 18.0%), vertigo (59.7% versus 26.8%), and headache (54.9% versus 45.3%), than in normal hearing diabetes. There were statistically significant differences between hearing impairment versus normal hearing for vitamin D [19.40±9.71 ng/ml versus 22.67±9.28 ng/ml; p
Kunio Hieshima , 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

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. 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. 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). 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.
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

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.
Pragati Garg , Smriti Misra, Swati Yadav, Luxmi Singh
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.
Hardeep Singh Dua, Manan Anand
International Journal of Advances in Medicine, Volume 4; doi:10.18203/2349-3933.ijam20175120

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.
Ruth E. Brown , Nikhil Gupta, Ronnie Aronson
Diabetes Technology & Therapeutics, Volume 19, pp 685-691; doi:10.1089/dia.2017.0134

The publisher has not yet granted permission to display this abstract.
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

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

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.
Published: 5 October 2017
Diabetes Therapy, Volume 8, pp 1215-1226; doi:10.1007/s13300-017-0302-3

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

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
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, Zhiwen Liu , Minghao Guo
Scientific Reports, Volume 7; doi:10.1038/srep44291

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

The publisher has not yet granted permission to display this abstract.
Ofri Mosenzon , Gil Leibowitz, Deepak L. Bhatt, Avivit Cahn , Boaz Hirshberg , 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

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.
Feng-Fei Li, Gu Gao, Qian Li, Hong-Hong Zhu, Xiao-Fei Su, Jin-Dan Wu, Lei Ye , Jianhua Ma
Published: 21 September 2016
Journal of Diabetes Research, Volume 2016, pp 1-6; doi:10.1155/2016/5347262

Objectives. To observe changes in blood glycemic variations and oxidative stress level before and after dapagliflozin treatment in patients with newly diagnosed T2DM. Methods. This was a randomized, double-blind, placebo-controlled, phase 3 trial. A total of 28 patients with newly diagnosed T2DM with HbA1c levels of 7.5–10.5% were randomly selected to receive dapagliflozin or placebo treatment for 24 weeks. After baseline data were collected, we analyzed glycemic variations and plasma 8-iso PGF2α level at baseline and at the endpoint. Primary outcome was the changes of mean amplitude glycemic excursion (MAGE) within groups. Results. After 24-week dapagliflozin therapy, our data showed the significant improvement of MAGE with dapagliflozin therapy (P = 0.010). Compared with control group, patients in dapagliflozin group exhibited reduction in 24-hour MBG (P = 0.026) and lower mean plasma glucose concentrations, especially during periods from 2400 to 0200 and 1300 to 1800 (P < 0.05, resp.). In addition, plasma 8-iso PGF2α level was notably decreased in the treatment group compared to the control group (P = 0.034). Conclusions. In conclusion, this study shows the ability of dapagliflozin to improve glycemic variations and associate with reduction of oxidative stress in patients with T2DM, which may benefit the cardiovascular system.
Amiroh Kurniati, Tahono Tahono
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY, Volume 21, pp 250-256; doi:10.24293/ijcpml.v21i3.736

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

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
Mohamed Abo El-Asrar, Nancy Samir Elbarbary , Eman Abdel Rahman Ismail, Alshaimaa Abo Bakr
Published: 28 May 2016
Angiogenesis, Volume 19, pp 421-431; doi:10.1007/s10456-016-9517-6

The publisher has not yet granted permission to display this abstract.
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

Agnieszka Zachurzok-Buczynska , Grazyna Deja, Aneta Gawlik, Agnieszka Drosdzol-Cop , Katarzyna Klimek, Ewa Malecka-Tendera
International Journal of Endocrinology, Volume 2016, pp 1-8; doi:10.1155/2016/9473158

Study Objectives. The study aim was to evaluate whether hyperandrogenemia in adolescent girls with type 1 diabetes mellitus (T1DM) may adversely influence lipid profile. Design and Participants. Lipid levels in 16 diabetic girls with biochemical hyperandrogenemia (T1DM-H) aged 16.3 ± 1.2 years were compared to 38 diabetic girls with normal androgen levels (T1DM-N) aged 15.8 ± 1.2 years. 15 healthy girls served as controls (CG). In all patients, anthropometric measurements were done, and androgens and SHBG were assessed. Results. In T1DM-H, total cholesterol (TC) and low density cholesterol (LDL-ch) were significantly higher than in CG (196.1 ± 41.2 versus 162.7 ± 31.7 mg/dL, p = 0.01; 117.3 ± 33.1 versus 91.3 ± 27.8 mg/dL, p = 0.01, resp.). Their LDL-ch, non-high density cholesterol (non-HDL-ch) concentrations, and LDL/HDL ratio were also significantly higher than in T1DM-N (117.3 ± 33.1 versus 97.7 ± 26.7 mg/dL, p = 0.03; 137.3 ± 42.9 versus 113.3 ± 40.4 mg/dL, p = 0.04; 2.8 ± 3.7 versus 1.6 ± 0.5, p = 0.04, resp.). In stepwise multiple linear regression, free androgen index (FAI) and waist-to-hip ratio (WHR) were associated with TC (R 2 = 0.4, p < 0.0006), non-HDL-ch (R 2 = 0.4, p < 0.0003), and LDL-ch (R 2 = 0.4, p < 0.0008). Triglycerides and LDL/HDL ratio were (R 2 = 0.7, p < 0.0001, R 2 = 0.6, p < 0.0003 resp.) related to testosterone, FAI, WHR, and mean HbA1c. Conclusion. Lipid profile in diabetic adolescent girls is adversely influenced by the androgens level, particularly in the group with higher WHR and poorer glycemic control.
Bedowra Zabeen, Maria E. Craig, Sohaib A. Virk, Alison Pryke, Albert K. F. Chan, Yoon Hi Cho, Paul Z. Benitez-Aguirre, Stephen Hing, Kim C. Donaghue
Published: 6 April 2016
PLoS ONE, Volume 11; doi:10.1371/journal.pone.0153033

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.
Nicole Prinz , 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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Rk Dubey , Sunita Neupane, Narayan Gautam , 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

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

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Satyajeet Roy , 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

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.
Francesco Zaccardi , Alessandro Rizzi, Giovanna Petrucci, Flavia Ciaffardini, Luigi Tanese, Francesca Pagliaccia, Viviana Cavalca, Angela Ciminello, Aida Habib, Isabella Squellerio , et al.
Published: 15 October 2015
Diabetes, Volume 65, pp 503-509; doi:10.2337/db15-0936

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.
Sripriya Raman , 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

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

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

Kumananda Acharya, Sangita Regmi, Alina Shri Sapkota, Mithileshwer Raut, Bharat Jha
Annals of Clinical Chemistry and Laboratory Medicine, Volume 1, pp 21-24; doi:10.3126/acclm.v1i1.12310

BACKGROUND: Diabetes mellitus (DM) is one of the most common endocrine disorders, characterized by hyperglycemia. Diabetic nephropathy is a consequence of long- standing diabetes and urinary microalbumin (Uma) status predicts progression to diabetic nephropathy. This study was conducted to know the status of Uma in relation to duration of diabetes and HbA1c level in patients with Type 2 diabetes mellitus (T2DM). METHODS: This prospective cross-sectional descriptive study was conducted from July 1, 2014 to January 15, 2015 at TUTH, Kathmandu. Ninety-six known T2DM patients with age 35– 83 years were included in the study. EDTA venous blood and spot urine sample were collected for analysis of HbA1c and Uma respectively. Only those patients having HbA1c concentration ≥ 6.3% and duration of diabetes ≥ 6 months were included under the study. RESULTS: Overall prevalence of microalbuminuria (MAU) was 39.6 %. MAU had a highly significant correlation with duration of diabetes (r =0.471, p0.05). CONCLUSIONS: Prolonged exposure to hyperglycemia-induced advanced glycosylation end products accumulations contributes for the development of MAU. So, duration of diabetes mellitus is main contributing factor for the development of MAU rather than HbA1c level alone. Screening for MAU to prevent renal impairment and measuring HbA1c level on a regular basis for good glycemic control are important in diabetic patients. DOI: Ann. Clin. Chem. & Lab. Med. 1(1) 2015: 21-24
Abdulmoein E. Al Agha , Maram Alafif, Ihab A. Abd-Elhameed
Published: 20 January 2015
Saudi Medical Journal, Volume 36, pp 26-31; doi:10.15537/smj.2015.1.9829

To investigate the relationship between metabolic control, acute and long-term complications, the coexistence of autoimmune diseases, and to assess the different factors that can affect the glycemic control level among children with type 1 diabetes mellitus (T1DM). This is a cross-sectional study that included 228 T1DM children and adolescents visiting the pediatric diabetes clinic at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from January 2013 to January 2014. The clinical and laboratory characteristics of the patients were recorded. Metabolic control, complications, and associated autoimmune diseases were evaluated. The mean age of patients was 10.99 years, and the glycated hemoglobin (HbA1c) level was 8.8%. Acute complications included ketoacidosis in 65.4% of patients, and hypoglycemic attacks in 68.9%. Long-term complications were detected in patients including retinopathy (4.4%), microalbuminuria (16.2%), and dyslipidemia (8.3%). Autoimmune thyroiditis was noted in 14%, and celiac disease was found in 19.7% of patients. A significant difference was found in pubertal and pre-pubertal age groups in terms of glycemic control (p=0.01). The level of HbA1c was found to be higher among the pubertal age group. A relationship between autoimmune diseases and gender was determined.
M J Hasan, A Muqueet, A Sharmeen, M R Hoque
Published: 1 January 2015
Mymensingh Medical Journal, Volume 24

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Sin Gon Kim , Jong Ryeal Hahm, Duk Kyu Kim, Sung Rae Cho, Dong Seop Choi
Published: 17 November 2014
by Wiley
Journal of Diabetes Investigation, Volume 6, pp 317-324; doi:10.1111/jdi.12284

To assess the current status of glycemic control in patients with type 2 diabetes treated with a combination of metformin and sulfonylurea for >3 months, as measured by glycosylated hemoglobin (HbA1c). Data on patient demographics, diabetic complications, HbA1c, fasting plasma glucose (FPG) and type of treatment were collected in this multicenter, cross-sectional, non-interventional study. From April 2008 to February 2009, 5,628 patients were recruited from 299 centers in Korea. Patients characteristics (mean ± SD) were as follows: age 58.4 ± 10.8 years, duration of diabetes 6.1 ± 4.7 years, body mass index 24.7 ± 2.9 kg/m2, HbA1c 7.77 ± 1.22%, FBG 147.4 ± 46.5 mmol/L and FPG 164.0 ± 54.3 mmol/L. The most common diabetic complication was neuropathy (22.5%), followed by retinopathy (18.3%) and microalbuminuria (16.1%). Just 1,524 (27.1%) patients achieved HbA1c ≤7%. A higher number of patients (32.6%) treated by endocrinologists achieved HbA1c ≤7% than those treated by internists (24.4%) and primary care physicians (23.2%). In multivariate analyses, diabetic retinopathy (odds ratio 0.455, 95% confidence interval 0.341–0.606), nephropathy (odds ratio 0.639, 95% confidence interval 0.43–0.949), diabetes for ≥5 years (odds ratio 0.493, 95% confidence interval 0.4–0.606) and older age added by 1 year (odds ratio 1.019, 95% confidence interval 1.01–1.029) was significantly associated with achieving target HbA1c. In addition, treatment by endocrinologists rather than internists significantly increased chances of achieving target HbA1c (odds ratio 1.417, 95% confidence interval 1.146–1.751). The majority of patients with type 2 diabetes in Korea had inadequate glycemic control, despite receiving a combination of metformin and sulfonylurea.
Iris Walraven , M. Ruth Mast, Trynke Hoekstra , A. P. Danielle Jansen, Amber A. W. A. Van Der Heijden, Simone P Rauh , Femke Rutters, Esther Van ’T Riet, Petra J. M. Elders, Annette C. Moll, et al.
Published: 8 October 2014
Acta Diabetologica, Volume 52, pp 267-275; doi:10.1007/s00592-014-0633-8

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Medicni perspektivi (Medical perspectives), Volume 19, pp 36-43; doi:10.26641/2307-0404.2014.3.30342

In the article defining relationship between endothelial dysfunction, the degree of renal and lipidemic profile damage in 234 patients with type 2 diabetes mellitus with hypertension was carried depending on the quality of glycemic control. It is shown that the deepening of endothelial dysfunction in patients with insufficient and poor compensation tightly correlates with the degree of renal and lipidemic disorders. In these patients there was a significant increase in the level of albuminuria, reduction in glomerular filtration rate, increase of concentrations of urea and creatinine. Against the background of poor hyperglycemia, compensation total cholesterol, low density lipoprotein content increases by 73,3% (p
Cuma Bulent Gul, Ozen Oz Gul, Soner Cander, Ayca Eroglu, Mustafa Hartavi, Nermin Keni, Aysenur Bayindir, Canan Ersoy, Erdinc Erturk, Ercan Tuncel, et al.
Published: 2 July 2014
Renal Failure, Volume 36, pp 1258-1262; doi:10.3109/0886022x.2014.938576

The publisher has not yet granted permission to display this abstract.
Sumana Narasimhan, Ruth S. Weinstock
Published: 1 June 2014
Mayo Clinic Proceedings, Volume 89, pp 806-816; doi:10.1016/j.mayocp.2014.01.009

Article Highlights▪Risk factors for the development of type 2 diabetes mellitus in youth are being overweight, having a family history of diabetes, race/ethnicity (black, Hispanic, American Indian, and Asian/Pacific Islander), having signs of insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic ovarian disease, and having been small for gestational age), and having a maternal history of diabetes or gestational diabetes during the child's gestation▪Metformin therapy is less effective in youth-onset diabetes compared with the adult onset, with poor durability of glycemic control observed in half of the youth in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study▪Deterioration in glycemic control in the TODAY study was associated with rapid loss of pancreatic beta cell function▪The addition of an intensive lifestyle change program to standard diabetes education and metformin therapy did not result in meaningful sustained weight loss and did not significantly improve glycemic control in youth in the TODAY study▪Hypertension, microalbuminuria, and dyslipidemia are common in youth-onset type 2 diabetes
Amanda Y. Wang, Meg Jardine, Vlado Perkovic
Managing Cardiovascular Complications in Diabetes pp 58-86; doi:10.1002/9781118337967.ch3

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Khalid Al-Rubeaan, Amira M. Youssef, Shazia N. Subhani, Najlaa A. Ahmad, Ahmad H. Al-Sharqawi, Hind M. Al-Mutlaq, Satish K. David, Dhekra AlNaqeb
Published: 21 February 2014
PLOS ONE, Volume 9; doi:10.1371/journal.pone.0088956

The prevalence of diabetic nephropathy and its risk factors have not been studied in a society known to have diabetes epidemic like Saudi Arabia. Using a large data base registry will provide a better understanding and accurate assessment of this chronic complication and its related risk factors. A total of 54,670 patients with type 2 diabetes aged ≥25 years were selected from the Saudi National Diabetes Registry (SNDR) and analyzed for the presence of diabetic nephropathy. The American Diabetes Association (ADA) criterion was used to identify cases with microalbuminuria, macroalbuminuria and end stage renal disease (ESRD) for prevalence estimation and risk factor assessment. The overall prevalence of diabetic nephropathy was 10.8%, divided into 1.2% microalbuminuria, 8.1%macroalbuninuria and 1.5% ESRD. Age and diabetes duration as important risk factors have a strong impact on the prevalence of diabetic nephropathy, ranging from 3.7% in patients aged 25–44 years and a duration of >5 years, to 21.8% in patients ≥65 years with a diabetes duration of ≥15 years. Diabetes duration, retinopathy, neuropathy, hypertension, age >45 years, hyperlipidemia, male gender, smoking, and chronologically, poor glycemic control has a significantly high risk for diabetic nephropathy. The prevalence of diabetic nephropathy is underestimated as a result of a shortage of screening programs. Risk factors related to diabetic nephropathy in this society are similar to other societies. There is thus an urgent need for screening and prevention programs for diabetic nephropathy among the Saudi population.
Hidenori Yoshii, Tomio Onuma, Tsutomu Yamazaki, Hirotaka Watada Md , Munehide Matsuhisa, Masayasu Matsumoto, Kazuo Kitagawa, Masafumi Kitakaze, Yoshimitsu Yamasaki, Ryuzo Kawamori
Journal of Atherosclerosis and Thrombosis, Volume 21, pp 563-573; doi:10.5551/jat.21626

Aim: The present study evaluated the effects of pioglitazone treatment on the incidence of primary cardiovascular events in Japanese subjects with type 2 diabetes mellitus at high risk of stroke.Methods: A prospective, multicenter, randomized, open label, comparative study was conducted among diabetic patients recruited from 50 medical institutions nationwide. A total of 522 patients with hypertension and/or dyslipidemia who had one or more silent cerebral infarcts, advanced carotid atherosclerosis or microalbuminuria at baseline were randomly treated with (n=254) or without pioglitazone (n=268) and observed for a medium of 672 days. The hypertension and dyslipidemia were concurrently treated according to the respective treatment guidelines. The primary outcome was the time to the first occurrence of a composite of all-cause death, nonfatal cerebral infarction and nonfatal myocardial infarction.Results: Treatment with pioglitazone resulted in significant reductions in the levels of HbA1c, diastolic blood pressure and LDL-cholesterol and a significant increase in the levels of HDL-cholesterol. The pioglitazone non-users exhibited a significant reduction in the LDL-cholesterol levels alone. Primary events were registered during the study period in nine patients in the pioglitazone group and 10 patients in the non-pioglitazone group. The difference in the cumulative incidence of the primary outcome was not significant between the two groups(1.8% per year).Conclusions: Pioglitazone therapy produces immediate and effective improvements in glycemic control, diastolic blood pressure and lipid profiles. While this study was too underpowered to determine the effects of pioglitazone on the incidence of cardiovascular events, the results indicated that two years of pioglitazone treatment did not produce any statistically significant reductions in the rate of primary cardiovascular events.
In-Ho Yang, Sun Hee Lee, Sang Ouk Chin, Suk Chon
Journal of Bone Metabolism, Volume 21, pp 283-289; doi:10.11005/jbm.2014.21.4.283

Patients with diabetes have many different kinds of complications involving multiple organs, but those involving the musculoskeletal system are relatively uncommon. Diabetic muscle infarction (DMI) is a rare, painful, and potentially serious condition in patients with poorly controlled diabetes mellitus. A 35-year-old man diagnosed with type 2 diabetes eight years ago, visited with severe muscle pain in the right anteromedial thigh without any event of trauma. He had been treated with metformin, but his glycemic control was very poor with a glycated hemoglobin of 14.5%. Evaluation of his painful thigh lesion did not reveal any evidence of infection or vasculitis, but the magnetic resonance imaging and bone scan showed findings of DMI at vastus medialis muscle and an insufficiency fracture at the right medial tibial condyle. He was diagnosed with retinopathy, neuropathy and microalbuminuria but not macrovascular complications. We also diagnosed his diabetes as latent autoimmune diabetes in adults (LADA) based on his low C-peptide level, positive anti-glutamic acid decarboxylase (GAD) antibody and early onset diabetes. Instead of antibiotics, bed rest, analgesics and strict blood glucose control with multiple daily insulin injections led to symptom improvement. This is an unusual case of a young man with LADA experiencing severe musculoskeletal complication of DMI and insufficiency fracture. If a poorly controlled diabetic patient appears to have unaccounted soft tissue pain, musculoskeletal complications such as DMI associated with hyperglycemia should be considered.
Wei-Zhi Chen, Cheng-Chieh Hung, Yu-Wen Wen, Hsiao-Chen Ning, Bing-Ru Gau, Yu-Yao Huang
Published: 13 September 2013
Renal Failure, Volume 36, pp 171-175; doi:10.3109/0886022x.2013.832312

This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of 60 mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10 mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC = 0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC = 0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR ( 8%, high-normal UACR/HbA1c < 8%, and high-normal UACR/HbA1c >8% were 2.59 (p = 0.107), 6.15 (p = 0.001), and 16.96 (p < 0.001), respectively. It was determined that an increase of HbA1c levels (10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.
JAMA Internal Medicine, Volume 173, pp 1682-1692; doi:10.1001/jamainternmed.2013.9051

In industrialized countries, as life expectancy increases and populations increase in age, type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Glycemic control, antihypertensive therapy, and inhibition of the renin-angiotensin system are known to affect established diabetic renal disease. However, little is known about the long-term effect of diet on the incidence and progression of early-stage diabetic CKD. The slow progression of CKD, the competing risk of death among individuals with diabetes and CKD, and the difficulty in assessing dietary intake contribute to this lack of information.
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