Knowledge, attitude and practices of insulin therapy among patients with type 2 diabetes: a cross-sectional study.

OBJECTIVES: This study aimed to assess the knowledge, attitude and practices of patients with type 2 diabetes on insulin regarding insulin therapy. DESIGN: A cross-sectional study. SETTING: This study was conducted at the Dubai Diabetes Center from 1 December 2018 to 1 March 2020. PARTICIPANTS: Face-to-face interviews were conducted for 350 participants with type 2 diabetes at the Dubai Diabetes Center. Interviews followed the structured format of a questionnaire designed to obtain demographic details and score participants on knowledge, attitude and practices. We included patients aged >18 years and receiving insulin therapy. Patients with type 1 diabetes, pregnant women with gestational diabetes, those aged <18 years or those with a history of dementia were excluded. RESULTS: The median age of participants was 61 years (first quartile, 53 years; third quartile, 67 years); 35.7% were male individuals and 64.3% were female individuals. The median percentage scores for knowledge, attitude and practices were 62.5% (62.5%, 75%), 85.7% (71.4%, 100%) and 77.7% (66.6%, 88.8%), respectively. Highly educated participants had a high level of knowledge. Significant negative correlations were found between the percentage knowledge scores and participants' age and between the participants' percentage attitude scores and haemoglobin A1C levels; Spearman's correlations were -0.182 (p<0.001) and -0.14 (p=0.008), respectively. A significant positive Spearman's correlation of 0.123 (p=0.021) was found between the percentage knowledge and percentage practice scores. No correlations were found among knowledge levels, participants' haemoglobin A1c levels and duration of insulin use. CONCLUSION: Patients with type 2 diabetes receiving insulin therapy and attending the Dubai Diabetes Center had adequate knowledge, a positive attitude and correct practice regarding insulin therapy. However, knowledge of specific facts did not always translate into correct behaviours and practices.

Real-World Study on Effectiveness of Insulin Glargine U300 After Oral Antidiabetic Drug Failure in Patients with Type 2 Diabetes in the Gulf Region.

INTRODUCTION: The effectiveness and safety of long-acting insulin glargine U300 (Gla-300), in patients with type 2 diabetes mellitus (T2DM) requiring insulin, has not been reported in the Gulf region. METHODS: Insulin-naïve patients with T2DM, uncontrolled on OADs, and prescribed Gla-300 were followed up in a 12-month prospective observational study. Gla-300 was titrated to glycemic targets. The primary endpoint (achieving glycemic targets) was evaluated at month 6 of treatment. The need for treatment intensification, safety, and patient-reported outcomes (PRO) were also reported. RESULTS: The study included 412 patients (61.7% men; age 52.2 ± 11.1 years and T2DM duration 10.7 ± 6.8 years). Almost 50% were on more than 3 OADs, mostly biguanides, sulfonylureas, and dipeptidyl-peptidase-4 inhibitors. Baseline HbA1c level was 9.2% ± 1.1% and targets were set at 6.9% ± 0.4%. Baseline fasting plasma glucose was 11.5 ± 3.8 mmol/l. Fifty-seven patients (13.8%) achieved glycemic targets at month 6, hindered by baseline HbA1c ≥ 10%, frequent co-morbidities, older age, suburban/rural residence, and full-time employment. Levels of HbA1c dropped progressively by 0.96% ± 0.07% (month 3), 1.29% ± 0.08% (month 6), and 1.76% ± 0.06% (month 12). Gla-300 dose was 17.0 ± 9.0 IU/day at baseline, 24.6 ± 9.6 IU/day at month 3, 28.5 ± 9.9 IU/day at month 6, and 30.7 ± 10.7 IU/day at month 12. Three patients experienced non-severe hypoglycemia and a slight decrease in body weight and PROs improved. CONCLUSIONS: In the Gulf, Gla-300 in patients with T2DM uncontrolled on OADs improved glycemic control, with low rates of hypoglycemia and improved PROs. Gla-300 dose up-titration from baseline to month 6 did not, however, result in a vast proportion of patients achieving their pre-determined HbA1c targets. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03703869.

Relationship Between Lipohypertrophy, Glycemic Control, and Insulin Dosing: A Systematic Meta-Analysis.

Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses.

Background: Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and ß-cell impairment lead to hyperglycemia, influenced by genetic and environmental factors. T2DM is associated with long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications to improve early diagnostic methods and treatment strategies. Methods: This cross-sectional study recruited 310 Emirati participants that were stratified according to their medically diagnosed diabetes-related complications: diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular complications. The Illumina's Infinium Exome-24 array was used and 39,840 SNPs remained for analysis after quality control. Findings: The analysis revealed the associations of various genes with each complication category: 1) diabetic retinopathy was associated to SHANK3 gene in locus 22q13.33 (SNP rs9616915; p=5.18 x10-4), ZSCAN5A gene in locus 19q13.43 (SNP rs7252603; p=7.55 x10-4), and DCP1B gene in locus 12p13.33 (SNPs rs715146, rs1044950, rs113147414, rs34730825; p=7.62 x10-4); 2) diabetic neuropathy was associated to ADH4 gene in locus 4q23 (SNP rs4148883; p=1.23 x10-4), SLC11A1 gene in locus 2q35 (SNP rs17235409; p=1.85 x10-4), and MATN4 gene in locus 20q13.12 (SNP rs2072788; p=2.68 x10-4); 3) diabetic nephropathy was associated to PPP1R3A gene in locus 7q31.1 (SNP rs1799999; p=1.91 x10-4), ZNF136 gene in locus 19p13.2 (SNP rs140861589; p=2.80 x10-4), and HSPA12B gene in locus 20p13 (SNP rs6076550; p=2.86 x10-4); and 4) cardiovascular complications was associated to PCNT gene in locus 21q22.3 (SNPs rs7279204, rs6518289, rs2839227, rs2839223; p=2.18 x10-4,3.04 x10-4,4.51 x10-4,5.22 x10-4 respectively), SEPT14 gene in locus 7p11.2 (SNP rs146350220; p=2.77 x10-4), and WDR73 gene in locus 15q25.2 (SNP rs72750868; p=4.47 x10-4). Interpretation: We have identified susceptibility loci associated with each category of T2DM-related complications in the Emirati population. Given that only 16% of the markers from the Illumina's Infinium Exome chip passed quality control assessment, this demonstrates that multiple variants were, either, monomorphic in the Arab population or were not genotyped due to the use of a Euro-centric EWAS array that limits the possibility of including targeted ethnic-specific SNPs. Our results suggest the alarming possibility that lack of representation in reference panels could inhibit discovery of functionally important loci associated to T2DM complications. Further effort must be conducted to improve the representation of diverse populations in genotyping and sequencing studies.

Needle Technology for Insulin Administration: A Century of Innovation.

Innovations in syringe and pen needle (PN) technology over the last 100 years have led to important advances in insulin delivery for people with diabetes, paralleling the strides made in developing recombinant DNA human insulin and insulin analogs with varying onset and duration of action. In this review, the history of advances in insulin delivery is described, focusing on progress in syringe, needle, and PN technologies. The early glass and metal syringes that required sterilization by boiling have been replaced by disposable, single-use syringes or pens with clear labeling for precise insulin dosing. The early needles ranging in length from 19 to 26 mm that required manual sharpening against a whetstone have been replaced by syringe needles of 6 mm and PNs of 4 mm in length as slender as 34 gauge. Imaging studies using ultrasound and computed tomography measured the thickness of skin and subcutaneous tissue layers to show feasibility of targeted insulin administration with shorter needles. These developments, coupled with innovations in needle/PN wall and tip structure, have led to improved injection experience for people with diabetes. It is also important to acknowledge the role of injection technique education, together with these advances in injection technology, for improving clinical outcomes and patient satisfaction. With continued projected growth of diabetes prevalence, particularly in developing countries where expensive and complex insulin delivery systems may not be practical, insulin syringes and pens will continue to serve as reliable and cost-effective means of insulin delivery for people with diabetes.

Prevalence of diabetes distress and depression and their association with glycemic control in adolescents with type 1 diabetes in Dubai, United Arab Emirates.

OBJECTIVE: Diabetes distress and depression have been shown to be prevalent among adolescents with type 1 diabetes and screening for these parameters should be a routine part of diabetes care. To assess the prevalence of diabetes distress and depression and their association with glycemic control in a sample of adolescents with type 1 diabetes attending a diabetes center in Dubai, United Arab Emirates. All adolescents aged 13 to 18 years with type 1 diabetes that were seeking treatment at the Dubai Diabetes Center from the period of September 1, 2018 to May 1, 2019. A total of 72 participants completed the study. RESEARCH DESIGN AND METHODS: Adolescents were asked to fill in questionnaires assessing diabetes distress and depression. Multivariate linear regression analysis was used to assess the relationships between the subsets of socio-demographic and clinical characteristics, and the scores of the questionnaires. RESULTS: The mean HbA1c of the study sample was 9.61% [82 mmol/mol] with higher levels found in females as compared with males (p<0.05). Females showed significantly greater levels of distress as compared with males. Although adolescents with HbA1c≥7.5% scored higher for diabetes distress and depression, the difference was not statistically significant to those with an HbA1c of <7.5%. Higher levels of diabetes distress were highly correlated with depressive symptoms, with distress and depression both being significant predictors of one another. CONCLUSIONS: Our results highlight the importance of implementing and sustaining psycho-educational interventions to aid in alleviating diabetes distress and depression in this subgroup of the population.

Association between type 2 diabetes mellitus & TCF7L2 gene variants in the Emirati population: Genetics of diabetes in the United Arab Emirates.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) has a multifactorial etiology involving a complex interplay between genes and the environment. The prevalence of T2DM among the countries of the Gulf Corporation Council (GCC), including the United Arab Emirates (UAE), ranks among the top 15 in the world. A number of studies have shown an increase in T2DM risk for the "TT" genotype at the rs4506565 and rs12255372 Single Nucleotide Polymorphisms (SNP) of the TCF7L2 gene. However, the association between TCF7L2 and T2DM still needs to be investigated in the UAE population. Therefore, this study analyzed the potential associations with rs4506565 and rs12255372 in UAE subjects. METHODS: For this case-control study, T2DM patients (n = 890) and healthy subjects (n = 686) were genotyped using a Taqman Real-Time PCR assay. Statistical analysis was performed with the resulting data using the R (version 3.3.1) and STATA (version 13) software packages. RESULTS: The rs12255372 SNP was significantly associated with T2DM (OR = 1.16, 95% CI = 1.00-1.34; P = .042). However, no significant association was found for the rs4506565 SNP (P = .120). After gender stratification, a significant association was found for both SNPs in males (Prs4506565 = .009 and Prs12255372 = .021). Interestingly, we found the interaction between the SNP rs4506565 with gender alone (P = .032) and in conjunction with BMI and age (P = .036) confers associations with T2DM. CONCLUSIONS: These findings suggest that the genetic variants of the TCF7L2 gene are associated with an increased susceptibility to T2DM, especially in Emirati males. Our study also highlights the impact of biological and environmental risk factors including age, BMI, and gender on the genetic susceptibility to T2DM.

Genetics of type 2 diabetes and coronary artery disease and their associations with twelve cardiometabolic traits in the United Arab Emirates population.

BACKGROUND: The United Arab Emirates (UAE) population has a high rate of type 2 diabetes mellitus (T2DM) and other metabolic risk factors for coronary artery disease (CAD). Previous studies have indicated strong genetic associations between T2DM and CAD. The objective of this study was to replicate previously reported significant genetic associations for T2DM and CAD which were in a genome-wide significance level in a cohort from the Arab population of the UAE, and to investigate the associations of these loci with twelve cardiometabolic traits that may influence the development of T2DM and CAD. METHODS: A total of nine hundreds and fourteen Emiratis were recruited to this study to investigate associations of 101 loci for T2DM (422 patients and 455 controls), and 53 loci for CAD (160 patients and 245 controls), using logistic regression models which incorporating possible confounding factors. Results are presented using odds ratios with their corresponding 95% confidence intervals and p-values. Linear regression models, which included possible covariates were applied to determine any associations between the T2DM and CAD reported loci with the twelve cardiometabolic traits and results were presented as effect sizes (beta), standard errors, and p-values. Furthermore, the overall risks for all the loci found to be associated with T2DM and CAD were determined using the cumulative effects of the risk alleles. For those found to be associated with the twelve cardiometabolic traits, risks were determined using calculations of their polygenic risk scores. RESULTS: The mean age of the T2DM group was 61.5 ± 11.3 and of the CAD group was 66.2 ± 9.3 years. The prevalence of most of the cardiovascular disease risk factors in this cohort were high: mean body mass index (BMI) = 29.4, T2DM (51.9%), hypertension (60.9%), dyslipidemia (68.8%), and smoking (47.9%). All individuals who were tested for CAD (n = 405) also had a diagnosis of T2DM. The highest association variant for T2DM was in SNP rs1977833 in HHEX (p = 0.0016, OR = 0.56 for allele A), which is a multi-ethnic locus for T2DM. The strongest association with CAD was detected with SNP rs264 in LPL, which encodes lipoprotein lipase (p = 0.009, OR = 1.96 for allele A). For the cardiometabolic traits analyses, most notable associations were those of FTO with BMI and waist circumference; ABO with height; KCNK16 with diastolic blood pressure; PROX1-AS1, GCKR, and MIR129-LEP with fasting blood glucose; random blood glucose with ZEB2 and THADA; HbA1c levels with TLE1 and FAM99B loci; HDL-cholesterol levels with BRAF; and triglyceride levels with ZEB2. Furthermore, accumulation of risk alleles and polygenic scores of the associated loci was clearly associated with increased risks for all tested diseases and traits in this cohort. CONCLUSIONS: The present study highlighted many known genetic loci, which are linked to T2DM and CAD and their associations with major cardiometabolic traits in Arab descendants. We confirmed that some loci are associated with T2DM, CAD, and metabolic traits independently of the ethnic background, with a novel association also detected between height and ABO.

Diagnosis and management of vitamin D deficiency in the Gulf Cooperative Council (GCC) countries: an expert consensus summary statement from the GCC vitamin D advisory board.

OBJECTIVE: A summary of recommendations is given within the Gulf Cooperation Council (GCC) setting on the assessment and management of vitamin D deficiency in the region. METHODS: An assembly of 11 regional experts gathered to formulate an all-inclusive approach to vitamin D deficiency within GCC. RESULTS AND CONCLUSION: Several gaps were identified before regional guidelines could be developed. These include adequacy and standardization of vitamin D testing, frequency of repeated testing and reference ranges, distinguishing prevention from the treatment of vitamin D deficiency, quality assurance of vitamin D products sold within GCC including contents and origins of products, and cut-points for vitamin D levels in local populations. A platform is created that can be further developed for overall regional implementation.

Mechanisms of action of metformin with special reference to cardiovascular protection.

Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin-stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin-based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

Patterns and trends in insulin initiation and intensification among patients with Type 2 diabetes mellitus in the Middle East and North Africa region.

AIM: Current and future estimates of the burden of diabetes in the Middle East and North Africa (MENA) region are among the highest in the world. VISION, an 18-month observational study, explored patterns of insulin initiation and intensification in T2DM patients in the MENA region. METHODS: 1192 patients aged ≥18 years were enrolled from Algeria, Egypt, Saudi Arabia and the UAE. Treating physicians recorded participants' data. Patient-reported outcomes (PROs) were assessed using questionnaires completed by participants. RESULTS: 67.6% patients had HbA1c ≥9% at insulin initiation, with a mean HbA1c of 9.9%, despite 68.3% patients being on ≥2 oral anti-diabetics, indicating a significant delay in insulin initiation. Basal insulin was initiated in 50.6% and premixed insulin in 46.3% patients. After 18 months, changes in insulin therapy were observed in 33.7% patients, while 39.6% patients achieved HbA1c levels of <7.5%. The proportion of patients completely satisfied with their insulin treatment, and the QoL increased over the study course. CONCLUSION: Results support that timely initiation and early intensification of insulin therapy are necessary in the region to achieve adequate and timely glycemic control and to prevent diabetic complications.

Prediabetes management in the Middle East, Africa and Russia: Current status and call for action.

Most data on the burden of diabetes and prediabetes are from countries where local infrastructure can support reliable estimates of the burden of non-communicable diseases. Countries in the Middle East and Africa, together with Russia, have a total population of almost 2 billion, but have been relatively overlooked by authors in this field. We reviewed the prevalence and drivers of prediabetes and diabetes across this large region. A large, and variable, burden of dysglycaemia exists, especially in Middle Eastern and North African countries, associated with high levels of obesity and sedentariness, with a generally lower prevalence in most other parts of Africa. The design and size of studies are highly variable, and more research to quantify the scale of the problem is needed. Local barriers to care relating to issues concerned with gender, consanguinity, lack of understanding of diabetes, lack of understanding of obesity as a health issue, and limited resource at a national level for tracking and intervention for diabetes and other non-communicable diseases. Lifestyle interventions with proven local cost-effectiveness, enhanced access to pharmacologic intervention, and societal interventions to promote better diet and more activity will be an important element in strategies to combat these adverse trends.

GOAL study: clinical and non-clinical predictive factors for achieving glycemic control in people with type 2 diabetes in real clinical practice.

OBJECTIVE: The American Diabetes Association and the European Association for the Study of Diabetes guidelines recommend to individualize treatment targets/strategies in inadequately controlled patients by lifestyle management and glucose-lowering drugs to decrease the burden of diabetes-related complications. This real-world practice study aimed to assess predictive factors for achieving the glycemic hemoglobin A1c (HbA1c) at 6 months as targeted by the treating physician in adults with type 2 diabetes who required initiation of basal insulin, initiation of bolus insulin, or modification from basal or premixed insulin to new insulin regimen containing insulin glargine and/or insulin glulisine. RESEARCH DESIGN AND METHODS: This was an international, multicenter, observational survey with 12-month follow-up time in adults with type 2 diabetes inadequately controlled conducted in 10 developing countries. RESULTS: Overall, 2704 patients (mean age: 54.6 years, body mass index: 28.7 kg/m2; Caucasian: 46.1%, type 2 diabetes duration: 10.1 years) with poor glycemic control (mean HbA1c: 9.7% (83 mmol/mol), fasting blood glucose: 196.8 mg/dL) were eligible. At 6 months, advanced age, Caucasian ethnicity, shorter type 2 diabetes duration (>10 vs 1 year, p<0.0001), lower baseline HbA1c (≥ 8.5% vs <7%, p<0.0001) and no intake of oral antidiabetic drug (OAD) (none vs 2, p=0.02) were predictive factors for achieving glycemic goal as targeted by the treating physician. Absolute changes in the mean HbA1c of -1.7% and -2% were observed from baseline to 6 and 12 months, respectively. CONCLUSIONS: Along with some well-known predictive factors, this study suggested that early insulin regimen treatment initiation and/or intensification allowed patients to promote glycemic control.

Self-efficacy, self-care and glycemic control in Saudi Arabian patients with type 2 diabetes mellitus: A cross-sectional survey.

AIMS: To determine the prevalence of diabetes self-care activities among type 2 diabetes patients and examine the association between socio-demographic and clinical parameters, diabetes self-care activities, and glycemic control among type 2 diabetes patients. METHODS: A cross sectional study was conducted among patients with diabetes (n = 123) at the Sultan Bin Abdulaziz Humanitarian City (SBAHC). A regression model was used to examine the variables that predicted glycemic control. Moreover, a regression analysis examining the effect of each self-efficacy subscale on its respective diabetes self -management (DSM) behavior was carried out. RESULTS: The most frequently reported DSM behaviors were foot care followed by medication taking self-management behavior. The least frequently reported DSM behaviors were exercise self-management behavior and blood sugar testing behavior. Self-efficacy was associated with higher levels of diet, exercise, blood sugar testing, and medication taking self-management behaviors. Diet self-management behaviors and oral hypoglycemic agents (OHA) use were significantly independent predictors of glycemic control HbA1c <7% (53 mmol/mol). CONCLUSIONS: The findings can serve to help clinicians have a better understanding on the extent to which different self-efficacy parameters have an influence on self-management behaviors, which will in turn lead to better glycemic control and thus improved HbA1c levels.

Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS).

AIMS: There is a large population of people with type 2 diabetes mellitus (T2DM) who are Muslim and fast during Ramadan. Changes in the pattern and amount of meal and fluid intake during Ramadan, in addition to the long fasting hours, may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. The Canagliflozin in Ramadan Tolerance Observational Study (CRATOS) evaluated the tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with sulphonylureas among patients with T2DM who fast during Ramadan. METHODS: This non-randomised, parallel-cohort, prospective, comparative, observational study was conducted in the Middle East during Ramadan and enrolled patients who were taking canagliflozin (n=162) or any sulphonylurea (n=159) added to metformin±dipeptidyl peptidase-4 inhibitor. The proportion of patients who experienced hypoglycaemia events was assessed as the primary end-point. Between-cohort comparisons were adjusted using propensity score analysis. RESULTS: During Ramadan, fewer patients experienced symptomatic hypoglycaemia with canagliflozin vs sulphonylurea (adjusted odds ratio: 0.273 [95% CI: 0.104, 0.719]). Of hypoglycaemia events for which blood glucose was measured, two of six with canagliflozin and 27 of 37 with sulphonylurea were confirmed by blood glucose <3.9 mmol/L. More patients treated with canagliflozin experienced volume depletion events compared with sulphonylurea (adjusted odds ratio: 3.5 [95% CI: 1.3, 9.2]). Missed fasting days were few and medication adherence was high in both groups. No patients treated with canagliflozin and 9.4% treated with sulphonylurea adjusted their medication dose near the beginning of Ramadan. Both treatments were generally well tolerated, with low rates of adverse events and no serious adverse events in either group. CONCLUSIONS: Overall, these findings support the use of canagliflozin for the treatment of adults with T2DM who fast during Ramadan. CLINICALTRIALS. GOV IDENTIFIER: NCT02737657.

The effect of vildagliptin relative to sulfonylurea as dual therapy with metformin (or as monotherapy) in Muslim patients with type 2 diabetes fasting during Ramadan in the Middle East: the VIRTUE study.

OBJECTIVE: To assess the effect of vildagliptin relative to sulfonylurea (SU) on hypoglycemic events, in Muslim patients from the Middle East with type 2 diabetes who fast during Ramadan. The primary endpoint was the proportion of patients with at least one hypoglycemic event (HE) during the fasting period. Secondary endpoints included change in weight, HbA1c levels, treatment adherence and overall safety. DESIGN AND METHODS: This multicenter, prospective, observational cohort study enrolled Muslim adult T2DM patients from Middle Eastern countries who received treatment with vildagliptin or SU as add on to metformin or monotherapy. During a ∼16 week observation period, data was collected up to 6 weeks before and 6 weeks after Ramadan fasting. RESULTS: A total of 584 patients from the Middle East enrolled in the study; 308 patients received vildagliptin and 265 received SU. Significantly fewer vildagliptin patients reported at least one HE (3.7% vildagliptin vs. 25.5% SU; p < .001). No grade 2 HEs were reported in vildagliptin patients versus two in SU patients (p = .128). Mean change in HbA1c at the end of study showed -0.18% between treatment difference in favor of vildagliptin, p = .001. Mean body weight change at the end of study showed -0.68 kg between treatment difference in favor of vildagliptin, p < .001. Treatment exposure and adherence were high and similar in both cohorts. There were 4.3% adverse events reported in vildagliptin compared to 25.3% in the SU cohort, with hypoglycemia being the most experienced event in both cohorts. LIMITATIONS: Being observational and not mandating HE confirmation with blood glucose measurement (though it was done in a large number of patients) were key limitations. CONCLUSION: Anti-hyperglycemic treatment with vildagliptin led to significantly fewer hypoglycemia events compared to sulfonylurea treatment among Muslim diabetic patients who fast during Ramadan. Good glycemic control, weight control and safety results supported this outcome.

Effects of vildagliptin relative to sulfonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: influence of age and treatment with/without metformin in the VIRTUE study.

BACKGROUND: VIRTUE was a prospective, observational study assessing the effectiveness and safety of vildagliptin vs sulfonylureas (SUs) (both as monotherapy and in combination with metformin) in patients with type 2 diabetes mellitus who fasted during Ramadan. A post hoc analysis was carried out to assess the effect of treatment with/without metformin and age (<65 years or ≥65 years). PATIENTS AND METHODS: Patients were recruited from the Middle East and Asia. The primary end point was proportion of patients with one or more hypoglycemic event (HE) during Ramadan. Secondary end points included change from baseline in glycated hemoglobin (HbA1c), body weight, and safety. RESULTS: Overall, 684 patients received vildagliptin and 631 received SUs. Most patients received dual therapy with metformin (n=1,148) and were aged <65 years (n=1,189). A few patients experienced one or more HE with vildagliptin vs SU monotherapy (6.5% vs 14.5%) and with vildagliptin + metformin vs SUs + metformin (5.3% vs 20.6%); the latter achieved statistical significance (P<0.001) in both age subgroups (<65 years: 5.5% vs 18.4%, P<0.001; ≥65 years: 2.8% vs 30.9%, P<0.001). Vildagliptin was associated with numerically greater HbA1c and body weight reductions vs SUs, regardless of the therapy type or age. A higher proportion of SU- vs vildagliptin-treated patients experienced adverse events across all subgroups. CONCLUSION: A few patients experienced HEs with vildagliptin vs SUs regardless of age, and in patients on dual therapy. Vildagliptin ± metformin was also associated with good glycemic and weight control and was well tolerated. Vildagliptin might be a useful treatment option for patients with type 2 diabetes mellitus, particularly high-risk populations such as the elderly fasting during Ramadan.

Association of Angiotensin Converting Enzyme Insertion-Deletion Polymorphism with Hypertension in Emiratis with Type 2 Diabetes Mellitus and Its Interaction with Obesity Status.

The association of Angiotensin Converting Enzyme (ACE) insertion-deletion (I/D) polymorphism with Type 2 Diabetes Mellitus (T2DM) and hypertension has been extensively studied throughout various ethnic populations but largely with inconsistent findings. We investigated these associations in Emirati population and their interaction with obesity status. Saliva samples were collected from a total of 564 Emiratis (277 T2DM and 297 healthy). DNA was extracted and the samples were genotyped for ACE I/D polymorphism by a PCR based method followed by gel electrophoresis. Upon evaluation of the ACE I/D polymorphism amongst all T2DM, hypertensive patients, and respective controls regardless of obesity status, ACE DD genotype was not found to be associated with either T2DM [odds ratio (OR) = 1.34, p = 0.086] or hypertension [odd ratio (OR) = 1.02, p = 0.93]. When the genetic variants amongst the nonobese and obese population were analyzed separately, the risk genotype ACE DD conferred significantly increased risk of hypertension in nonobese population [odds ratio (OR) = 1.80, p = 0.02] but was found to be protective against the hypertension in the obese group ((OR) = 0.54, p = 0.01). However, there was no effect of obesity status on the association of ACE genotypes with T2DM. The risk of hypertension associated with ACE DD is modulated by obesity status and hence future genetic association studies should take obesity into account for the interpretation of data. We also confirmed that ACE I/D polymorphism is not associated with T2DM risk in Emirati population.

Driving and diabetes mellitus in the Gulf Cooperation Council countries: Call for action.

The aim of the present article is to increase awareness concerning safe driving for patients with diabetes in the Gulf Cooperation Council (GCC) countries and to provide recommendations concerning the management of these patients. The cognitive, motor, and sensory skills required for driving can be adversely affected by diabetes as well as the side effects of anti-diabetic medications, particularly hypoglycemia. The prevalence of diabetes in the GCC countries is among the highest in the world. As the number of diabetic drivers in these countries continues to increase, the number at risk of having a motor vehicle accident is also expected to increase. We reviewed the available literature concerning driving and diabetes, particularly in relation to the current situation in the GGC countries. Unfortunately, very little published information is available addressing this issue in the GCC countries. Most of the GCC countries lack legislation on driving and diabetes. We have proposed recommendations to help diabetic drivers in the GCC countries as well as to provide guidance to health care professionals managing these patients.