Association of urinary non-albumin protein with the different urinary marker for glomerular and tubular damage in patients with type 2 diabetes.

BACKGROUND/AIM: In recent years, the diagnostic utility of urinary protein levels has been demonstrated for the early detection and progression of kidney disease. This study aimed to evaluate the associations of the non-albumin protein (NAP) with different urinary marker for tubular and glomerular damage in patients with type 2 diabetes (T2D). METHODS: In this observational cross-sectional study, 424 patients with T2D duration > 10 years were classified into two groups according to estimated glomerular filtration rate (eGFR). The ratios of different urinary markers (albumin, NAP, total protein, transferrin, retinol-binding protein (RBP), and neutrophil gelatinase-associated lipocalin (NGAL) to creatinine were analyzed. RESULTS: The levels of urinary biomarkers increased significantly with decrease in eGFR levels. In the group with moderately decreased eGFR, the albumin to-creatinine ratio (ACR), non-albumin protein-to-creatinine ratio (NAPCR), and total protein-to-creatinine ratio (PCR) were independently associated with all urinary markers after being adjusted for risk factors. The area under the receiver operating characteristics (ROC) curve for ACR and PCR had a better diagnostic value than other urinary biomarkers. Comparing ROC curve of NAPCR with other urinary biomarkers, it was significantly better than NGAL/Cr (p = 0.033). CONCLUSIONS: The findings of the present study confirm that ACR and PCR are diagnostic biomarkers in T2D patients with decreased eGFR. NAPCR in these patients diagnostically only outperformed NGAL/Cr.

Association between serum uric acid levels and metabolic markers in patients with type 2 diabetes from a community with high diabetes prevalence.

BACKGROUND: The importance of uric acid has been increasingly appreciated because of its association with the development of diabetes mellitus and related diseases. OBJECTIVE: This study was undertaken to evaluate the association of serum uric acid (SUA) level with different clinical and biochemical parameters in patients with type 2 diabetes from Saudi Arabia. METHODS: Clinical and biochemical data from the patients were obtained and assessed in a cross-sectional design. Relationships between SUA level and various clinical and biochemical parameters were analysed. RESULTS: SUA level was positively associated with increased incidence of cardiovascular diseases (CVD) in patients with abnormal eGFR (<90 mL/min/1.73 m2 ). HbA1c was found to be inversely associated with hyperuricemia in patients with normal eGFR level (≥90 mL/min/1.73 m2 ). Incidence of metabolic syndrome did not show any relationship with SUA level. However, the incidence of hypertension, a component of metabolic syndrome, was significantly higher among patients with hyperuricemia. Waist circumference and serum triglycerides were higher, whereas serum high-density lipoprotein level was lower in patients with higher SUA level. Patients with hyperuricemia had higher incidence of CVDs than those of the normouricemic group. CONCLUSION: SUA level was positively associated with incidence of cardiovascular diseases CVD in patients with abnormal eGFR. HbA1c correlated significantly with SUA level in patients with normal eGFR. Incidence of metabolic syndrome did not show any association with SUA level. Incidence of hypertension, waist circumference and serum triglycerides were significantly higher and serum high-density lipoprotein level was lower in patients with higher SUA level.

Physicians' choices in the first- and second-line management of type 2 diabetes in the Kingdom of Saudi Arabia.

OBJECTIVES: The DISCOVER study is a global, prospective, three- year- observational (non-interventional) study that was conducted in 37 countries throughout the world including Saudi Arabia and aimed to assess variations in treatment patterns and therapeutic outcomes in type 2 diabetic patients. The current manuscript is reporting data of DISCOVER study across different health sectors of various provinces in the Kingdom of Saudi Arabia. METHODS: In this study, 519 Saudi type 2 diabetics, non-insulin users, aged 18 years or older, initiating second line therapy, were selected from nine health institutes, in four out of five provinces in Saudi Arabia. Data was collected at baseline (initiation of 2nd line therapy) by the treating physician using an electronic case report form (eCRF) via a web-based data capture system. Each selected subject was asked to complete four self-administered questionnaires. RESULTS: The mean age of the studied population was 52.4 ± 11 years. Among the subjects selected from the nine medical centers, 55% were men, with almost 65% between the ages of 46 and 65 years. The oral agent used as 1st line in the majority of patients was metformin, prescribed in 89.2% of the study cohort. In the second line, sitagliptin was the most frequently used, at 61.8%. followed by gliclazide, glibenclamide, and glimepiride at 35.6%, 13.1%, and 12.7%, respectively. CONCLUSION: Metformin, with or without sulfonylureas, is the most commonly prescribed first-line treatment for patients with type 2 diabetes, managed either in governmental institutions, or in the private sector. The most common second line drugs were DPP4 inhibitors, mainly sitagliptin, followed by the third and second generation of sulfonylureas. Drug affordability was not an issue, since the vast majority of the patients received medication free of charge.

Relative reduction of biological and phylogenetic diversity of the oral microbiota of diabetes and pre-diabetes patients.

BACKGROUND: A reciprocal relationship between oral health and systemic disease, such as type 2 diabetes, has been suggested, whereby a systemic disease is a predisposing factor for oral infection. If the infection occurs, it in turn aggravates the progression of the systemic disease. According to several studies, certain constituents of the oral microbiota are linked to diabetes, metabolic syndrome, and obesity. In the current study, we aimed to compare the microbial diversity and population structure of the oral microbiota of normoglycemic, impaired glucose tolerance (IGT), and diabetes patients. METHODOLOGY: The study followed a case-control design, with 15 type 2 diabetes patients, 10 IGT subjects, and 19 control subjects. All subjects underwent assessment of periodontitis and oral health. Saliva samples were collected, and DNA was isolated from these samples. Hypervariable regions of the 16Sr RNA gene were amplified and sequenced, and the generated sequences underwent bioinformatics analysis. Statistical analysis and diversity index calculations were made using the statistical software R, vegan R-package, and Past3.20 software. RESULTS: Overall, 551 operational taxonomic units (OTUs) were identified. Based on OTU analysis, a clear reduction of the number of species was observed in both IGT (412) and diabetes groups (372) compared with that in the normoglycemic group (502). This was associated with a similar pattern of reduction of biological diversity among the three groups. The phylogenetic diversity (PD-SBL) value in the normoglycemic group was higher than that in the diabetes group. The diabetes group exhibited the highest evenness value and the highest microbiota bacterial pathogenic content. CONCLUSION: A clear reduction of the biological and phylogenetic diversity was apparent in the diabetes and pre-diabetes oral microbiota in comparison with that in the normoglycemic oral microbiota. However, this was associated with an increase in the pathogenic content of the hyperglycemic microbiota. The results of this study may aid to better understanding of the directionality of the mysterious reciprocal relationship.

Serum Sex Hormone Binding Globulin (SHBG) Relation with Different Components of Metabolic Syndrome in Men with Type 2 Diabetes.

Sex hormone binding globulin (SHBG) is demonstrated to be decreased in subjects with metabolic syndrome (MetS). The aim of the present study was to investigate the association of SHBG in relation to MetS components among men with type 2 diabetes (T2D). This cross-sectional study was carried out among 429 Saudi T2D male patients aged >30 years. Metabolic syndrome was defined using International Diabetes Federation (IDF) criteria. Fasting blood glucose (FBG), HbA1c, albumin, and lipid parameter were measured. Gonadal hormones, namely total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG were determined using ELISA. The SHBG levels of the MetS group was significantly lower than non-MetS group 47.25±31.03 nmol/l vs. 56.55±37.84 nmol/l; p=0.013. As the MetS score increases, SHBG and HDL levels decrease while weight, BMI, waist circumference, SBP, DBP, FBG, HbA1c, TC, and TG levels increase. SHBG correlated with age, BMI, TG, HDL, TT, free testosterone, and bio-available testosterone. This is the first study that provides detailed analyses of SHBG with MetS components in male diabetic subjects. The mean serum SHBG levels gradually declined with the addition of MetS components in T2D men. TT, free testosterone, and bio-available testosterone remained independently associated with SHBG by multivariable regression analysis.

ASSESSMENT OF KNOWLEDGE, ATTITUDE AND PRACTICE TOWARDS CONSANGUINEOUS MARRIAGES AMONG A COHORT OF MULTIETHNIC HEALTH CARE PROVIDERS IN SAUDI ARABIA.

This study aimed to assess knowledge, attitude and practice related to consanguinity among multiethnic health care providers in the Kingdom of Saudi Arabia. Using a cross-sectional study design, a validated, self-administered close-ended questionnaire was randomly distributed to health care providers in different health institutions in the country between 1st August 2012 and 31st July 2013. A total of 1235 health care providers completed the study questionnaire. Of the 892 married participants (72.23% of total), 11.43% were married to a first cousin, and were predominantly Arabs, younger than 40 years and male. Only 17.80% of the patients seen by the health care providers requested consanguinity related counselling. A knowledge barrier was expressed by 27.49% of the participants, and 85.67% indicated their willingness to have more training in basic genetic counselling. A language barrier was expressed as a limiting factor to counselling for consanguinity among non-Arabs. The health care providers had a major dearth of knowledge that was reflected in their attitude and practice towards consanguinity counselling. This finding indicates the need for more undergraduate and postgraduate medical and nursing education and training in the counselling of consanguineous couples. It is recommended that consanguinity counselling is included in the current premarital screening and counselling programmes in the Kingdom.

A null mutation in TNIK defines a novel locus for intellectual disability.

Intellectual disability (ID) is one of the most common disabilities and, although many genes have been implicated in its etiology, the genetic heterogeneity of ID continues to expand. The purpose of the study was to describe a novel autosomal recessive non-syndromic ID locus. Autozygome and linkage analysis, and exome sequencing followed by RNA and protein analysis of the candidate disease gene were performed. We describe two multiplex consanguineous families with non-syndromic ID phenotype, which maps to a critical linkage locus on 3q26. Exome sequencing of the index in each family revealed the same homozygous truncating mutation in TNIK that results in complete loss of the protein. TNIK is a kinase with a well-established role in dendrite development and synaptic transmission. The phenotype we observe in human patients who lack TNIK is consistent with the previously published Tnik (-/-) phenotype in the murine model. Our data strongly implicate TNIK deficiency in the causation of ID in humans.

Assessment of the prevalence and risk factors of ophthalmoplegia among diabetic patients in a large national diabetes registry cohort.

BACKGROUND: There are limited data on the epidemiology and risk factors of ophthalmoplegia among diabetic patients. This study aims to determine the prevalence and important risk factors related to ophthalmoplegia among diabetic patients. METHODS: This is an observational registry-based study using the Saudi National Diabetes Registry (SNDR) database to select diabetic patients regardless of their diabetes type. A total of 64,351 Saudi diabetic patients aged more than 18 years and registered in SNDR between January 2000 and December 2010 were analyzed to identify ophthalmoplegic cases. Demographic, clinical, and biochemical parameters were studied and STROBE guidelines were used to design and report the results of this study. RESULTS: The overall prevalence of ophthalmoplegia cases was 0.32 %, further distributed into: 53.11 %, 36.36 %, and 2.8 % for cranial nerves VI, III, IV palsies respectively. Ophthalmoplegic cases were predominantly type 2 diabetic males with older age and longer diabetes duration. The most important and significant risk factors were age ≥ 45 years, diabetes duration ≥ 10 years, male gender and presence of retinopathy and nephropathy. CONCLUSIONS: Ophthalmoplegia is a rare entity associated mainly with type 2 diabetes. Clinicians have to consider its risk factors when screening or planning for prevention of this condition.

Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries.

BACKGROUND: Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. METHODS AND RESULTS: The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. CONCLUSIONS: Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Residual macrovascular risk in 2013: what have we learned?

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.

Production of silver nanoparticles with strong and stable antimicrobial activity against highly pathogenic and multidrug resistant bacteria.

AIMS: To synthesize, characterize, and analyze antimicrobial activity of AgNPs of Escherichia hermannii (SHE), Citrobacter sedlakii (S11P), and Pseudomonas putida (S5). METHODS: The synthesized AgNPs were examined using ultraviolet-visible spectroscopy (UV-vis) and, zeta potential, and the size and the morphology obtained from the three different isolates were also confirmed by TEM. RESULTS: Among the three isolates tested, SHE showed the best antimicrobial activity due to the presence of small (4-12 nm) and stable (-22 mV) AgNPs. Stability of AgNPs was also investigated and found to be dependent on the nature of isolates. CONCLUSION: Produced AgNPs showed particle stability and antimicrobial efficacy up to 90 days of production. Our AgNPs exhibited greater antimicrobial activity compared with gentamicin against P. aeruginosa isolates and vancomycin against S. aureus and MRSA isolates at very low concentration (0.0002 mg per Microliters).

Prevalence of urinary tract infection and risk factors among Saudi patients with diabetes.

PURPOSE: The aim of this study is to assess the prevalence of urinary tract infection (UTI) and its risk factors among Saudi diabetics. METHOD: A total of 1,000 diabetic patients were included. Patients were interviewed and examined at each visit every 6 months. RESULTS: The prevalence of UTI was 25.3 % in total diabetic population and 7.2 and 41.1 % in males and females, respectively. Females have highest risk of UTI (RR = 6.102; CI = 4.343-8.573; P < 0.001). Age, duration of diabetes and HbA1c did not influence the incidence of UTI, while BMI above 30 kg/m(2) increased the risk (RR = 1.722; CI = 1.532-1.935; P < 0.001). The incidence of UTI in both type 1 and 2 diabetics was similar (23.7 and 25.6 %). There was no significant risk in patients aged above 60 years (RR = 1.054; CI = 0.841-1.321; P = 0.651). The risk factors found to be associated with UTI were hypertension (RR = 1.202; CI = 1.061-1.361; P = 0.006), insulin therapy (RR = 1.411; CI = 1.262-1.578; P < 0.001) and nephropathy (microalbuminuria) (RR = 1.417; CI = 1.036-1.939; P = 0.031). CONCLUSION: The present study has shown that prevalence of UTI is more in diabetic females and diabetics with BMI above 30 kg/m(2). The other risk factors associated with UTI in general diabetic population were found to be microalbuminuria, hypertension and insulin therapy.

A Web-based interactive diabetes registry for health care management and planning in Saudi Arabia.

BACKGROUND: Worldwide, eHealth is a rapidly growing technology. It provides good quality health services at lower cost and increased availability. Diabetes has reached an epidemic stage in Saudi Arabia and has a medical and economic impact at a countrywide level. Data are greatly needed to better understand and plan to prevent and manage this medical problem. OBJECTIVE: The Saudi National Diabetes Registry (SNDR) is an electronic medical file supported by clinical, investigational, and management data. It functions as a monitoring tool for medical, social, and cultural bases for primary and secondary prevention programs. Economic impact, in the form of direct or indirect cost, is part of the registry's scope. The registry's geographic information system (GIS) produces a variety of maps for diabetes and associated diseases. In addition to availability and distribution of health facilities in the Kingdom, GIS data provide health planners with the necessary information to make informed decisions. The electronic data bank serves as a research tool to help researchers for both prospective and retrospective studies. METHODS: A Web-based interactive GIS system was designed to serve as an electronic medical file for diabetic patients retrieving data from medical files by trained registrars. Data was audited and cleaned before it was archived in the electronic filing system. It was then used to produce epidemiologic, economic, and geographic reports. A total of 84,942 patients were registered from 2000 to 2012, growing by 10% annually. RESULTS: The SNDR reporting system for epidemiology data gives better understanding of the disease pattern, types, and gender characteristics. Part of the reporting system is to assess quality of health care using different parameters, such as HbA1c, that gives an impression of good diabetes control for each institute. Economic reports give accurate cost estimation of different services given to diabetic patients, such as the annual insulin cost per patient for type 1, type 2, and gestational diabetes, which are 1155 SR (US $308), 1406 SR (US $375), and 1002 SR (US $267), respectively. Of this, 72.02% of the total insulin cost is spent on type 2 patients and 55.39% is in the form of premixed insulin. The SNDR can provide an accurate assessment of the services provided for research purposes. For example, only 27.00% of registered patients had an ophthalmic examination and only 71.10% of patients with proliferative retinopathy had laser therapy. CONCLUSIONS: The SNDR is an effective electronic medical file that can provide epidemiologic, economic, and geographic reports that can be used for disease management and health care planning. It is a useful tool for research and disease health care quality monitoring.

Longitudinal assessment of the quality of life and patterns of antidiabetic medication use in patients with type 2 diabetes, Saudi Arabia perspective, DISCOVER study.

OBJECTIVES: Patients with type 2 diabetes nowadays have a wide range of new antidiabetic medications with better efficacy and safety. Physicians' attitude toward selecting antidiabetic medications to reach targeted glycemic control and better quality of life (QOL) has not been studied prospectively. The global DISCOVER study aims to comprehensively provide a real-world assessment of the treatment pattern changes for patients with type 2 diabetes, in addition to QOL assessment. The Kingdom of Saudi Arabia was one of the countries participating in the DISCOVER study program. METHODS: This study is a part of the prospective, longitudinal multinational DISCOVER study conducted in 38 countries including Saudi Arabia, a country facing an epidemic of type 2 diabetes, recruited 519 adult patients with type 2 diabetes with a mean age of 52.4 ± 11 years, where, they were followed up for three years period, where 477 patients completed the follow-up period. The clinical, biochemical, and patient lifestyle data were assessed periodically during the study period. DISCOVER study is registered with ClinicalTrials.gov identifiers: NCT02322762. RESULTS: The most frequently used antidiabetic medications (ADMs) initially and during the follow-up were biguanides (metformin) and sulfonylureas (gliclazide, glibenclamide, glimepiride, glipizide, and glyclopyramide). Insulin (premix Insulin, basal insulin, and basal/bolus insulin) and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, and linagliptin) were the most frequent second and alternative of therapy. Other medications namely thiazolidinediones (TZds) (pioglitazone and rosiglitazone), incretins (exenatide and liraglutide), and Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (canagliflozin) were used at a lesser rate. Drug availability, efficacy, and safety were the main determinants for choosing antidiabetic medications. The physical component score of the QOL had shown a significant decrease, while the mental component score has demonstrated an increase in QOL using SF36v2 Survey. CONCLUSIONS: There is an increasing trend of using of newly available ADMs, mainly DPP-4 inhibitors. The major limitation of ADMs use is related to efficacy, availability, and safety. This warrant taking all the measures to overcome these limitations through adopting a multidisciplinary team approach for close monitoring of the patients and any unfavorable side effects. Additionally, global insurance coverage for all patients with type 2 diabetes could be a solution for the drug availability factor.

Metabolic control and incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy: an analysis of the Saudi Arabia data from the DISCOVER Observational Study programme.

OBJECTIVES: The aim of the global DISCOVERing Treatment Reality of Type 2 Diabetes in Real World Settings (DISCOVER) Study was to provide a comprehensive real world assessment of the treatment pattern changes for patients with type 2 diabetes. The aim of this analysis was to assess the metabolic control and the annual incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy. DESIGN: This study is part of the observational, longitudinal, prospective multinational DISCOVER Study. SETTING: Governmental and private health sectors from different regions within Saudi Arabia. PARTICIPANTS: The study recruited 519 patients with type 2 diabetes aged ≥18 years who were switching to second-line therapy. Patients who were already using insulin/injectable agents, patients with type 1 diabetes, pregnant women, and patients undergoing dialysis or with a history of renal transplantation were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Metabolic control among patients with type 2 diabetes mellitus; fear of hypoglycaemia; quality of life; and the incidence of complications, hypoglycaemic events and/or hospitalisations. Data were analysed using descriptive statistics. RESULTS: A total of 519 patients were recruited with a mean age of 52.4±11 years. Of these participants, 54.7% were male and 45.3% were female. The incidence of hypoglycaemia was 56.72/1000 patient-years. The Hypoglycemia Fear Survey II showed a significant increase in patient worry related to hypoglycaemia from 6.4±11.9 at baseline to (p=0.0446) at the 36-month follow-up. The incidence of hospitalisation was 30.81/1000 patient-years. There was a moderate improvement in glycaemic control, represented as an HbA1c reduction from 8.8% at baseline to 8.2% at the 36-month follow-up. The incidence of macroangiopathy was 24.51/1000 patient-years and the incidence of microvascular complications such as retinopathy and albuminuria was 47.00/1000 patient-years and 221.71/1000 patient-years, respectively. The mean score of fear of hypoglycaemia showed an increase with 13.0±21.5 at baseline to 16.1±22.2 at the 36-month follow-up. When assessing the patients' quality of life, there was an improvement in the mental component score from 47.4±9.1 at baseline to 53.0±6.7 at the 36-month follow-up. CONCLUSIONS: Treatment intensification decisions should be made individually, weighing the benefit of good glycaemic control against the risk of hypoglycaemia. TRIAL REGISTRATION NUMBER: NCT02322762 and NCT02226822.

Rapid and simple preparation of a reagentless glucose electrochemical biosensor.

A rapid and simple procedure was developed for the preparation of a highly stable and leach-proof glucose oxidase (GOx)-bound glassy carbon electrode (GCE). Crosslinked GOx via glutaraldehyde was drop-cast on a KOH-pretreated GCE followed by drop-casting of 3-aminopropyltriethoxysilane (APTES) to form a stable bioactive layer. At -0.45 V, the biosensor exhibited a wide dynamic detection range of 0.5-48 mM for commercial glucose and 1.3-28.2 mM for Sugar-Chex blood glucose linearity standards. Several endogenous electroactive substances and drug metabolites commonly found in blood were tested and provoked no signal response. To our knowledge, the developed procedure is the most rapid method for preparing a glucose biosensor. The biosensor suffered no biofouling after 7 days of immersion in Sugar-Chex blood glucose. With excellent production reproducibility, GOx-bound electrodes stored dry at room temperature retained their initial activity after several weeks.

Efficacy and Safety of Insulin Glargine 300 U/mL in People with Type 2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

INTRODUCTION: The efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa. METHODS: The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5-10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed. RESULTS: A total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (- 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event. CONCLUSION: In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions. GOV IDENTIFIER: NCT03760991.

Prevalence and risk factors of vascular complications in type 2 diabetes mellitus: Results from discover Middle East and Africa cohort.

Background: We evaluated the prevalence of vascular complications and associated risk factors in individuals with type 2 diabetes mellitus (T2DM) initiating second-line glucose-lowering therapy from the Middle East and Africa (MEA) cohort of the 3-year prospective DISCOVER study involving 15,992 patients in 38 countries. Methods: Baseline cross-sectional data collected from healthcare settings were used to assess micro and macrovascular complications prevalence as crude and age- and sex-standardised. The multi-variable analysis assessed factors associated with these complications. Results: Of 3,525 enrolled patients (mean age: 54.3 ± 10.8 years), >40% had hypertension and hyperlipidaemia. Metformin monotherapy was the first-line therapy in 56.5%, followed by metformin+sulphonylurea (20.3%). Crude and standardised prevalence of microvascular complications were 17.7% and 16.9% (95% confidence interval [CI], 16.77-16.98) and macrovascular complications were 10.7% and 8.7% (95% CI, 8.59-8.76). Factors significantly (p<0.05) associated with micro and macrovascular complications (odds ratios [95% CI]) were age (1.24 [1.12-1.39] and 1.58 [1.35-1.84]), male sex (1.33 [1.04-1.70] and 1.71 [1.22-2.40]), hyperlipidaemia (1.33 [1.07-1.65] and 1.96 [1.46-2.63]) and hypertension (1.75 [1.40-2.19] and 2.84 [2.07-3.92]). Conclusion: A substantial burden of vascular complications with prominent risk factors in the MEA cohort calls for early preventive interventions.

Characteristics and Treatment Patterns of Patients with Type 2 Diabetes Mellitus in the Middle East and Africa Cohort of the DISCOVER Study Program: a Prospective Study.

INTRODUCTION: Despite the high prevalence of type 2 diabetes (T2D) and suboptimal glycemic control in the Middle East and Africa, comprehensive data on the management of T2D remain scarce. The main aim of this study is to describe the characteristics and treatment of patients with T2D initiating second-line glucose-lowering therapy in these regions. METHODS: DISCOVER is a global, 3-year, prospective observational study of patients with T2D enrolled at initiation of second-line glucose-lowering therapy. Baseline characteristics and treatments are presented for patients from 12 countries divided into three regions: Mediterranean, Gulf Cooperation Council, and South Africa. RESULTS: Among 3525 patients (52.5% male, mean age 54.3 years), mean time since T2D diagnosis was 6.2 years [across-region range (ARR) 5.8-7.5 years] and mean glycated hemoglobin levels were 8.7% (72.0 mmol/mol) [ARR 8.6-9.0% (68-75 mmol/mol)]. At first line, metformin was prescribed for 88.1% (ARR 85.4-90.3%) of patients and a sulfonylurea for 34.4% (ARR 12.7-45.4%). Sulfonylureas and dipeptidyl peptidase-4 inhibitors were prescribed at second line for 55.5% (ARR 48.6-82.5%) and 49.0% (ARR 3.7-73.8%) of patients, respectively. Main reasons for choice of second-line therapy were efficacy (73.2%; ARR 60.1-77.7%) and tolerability (26.8%; ARR 3.7-31.2%). CONCLUSIONS: We demonstrate considerable inter-region variations in the management of T2D, likely affected by multiple factors (health system, physician behavior, and patient compliance), all of which should be addressed to optimize outcomes.