Efficacy and Safety of a Biosimilar Liraglutide (Melitide®) Versus the Reference Liraglutide (Victoza®) in People with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Noninferiority Clinical Trial.

INTRODUCTION: Liraglutide effectively controls blood glucose level and reduces body weight. The aim of this study was to compare the efficacy and safety of a biosimilar liraglutide (Melitide®; CinnaGen, Tehran, Iran) to the reference liraglutide (Victoza®; Novo Nordisk, Bagsvaerd, Denmark) in people with type 2 diabetes mellitus (T2DM). METHODS: In this phase 3 clinical noninferiority trial, adult patients with inadequately controlled T2DM and with hemoglobin A1C (HbA1C) levels of 7-10.5% on at least two oral glucose-lowering drugs with stable doses for at least 3 months were randomized to receive Melitide® (n = 150) or Victoza® (n = 150) 1.8 mg/day for 26 weeks. The primary outcome was assessment of the noninferiority of Melitide® to Victoza® in terms of change in HbA1C level with a prespecified margin of 0.4%. The secondary outcomes were the assessment of additional efficacy parameters (including the proportion of patients achieving HbA1C levels of < 7%), the incidence of adverse events, and immunogenicity. RESULTS: Of the 300 participants enrolled in this study, 235 were included in the per-protocol analysis (112 in the Melitide® group and 123 in the Victoza® group). The mean (standard deviation) changes in HbA1C were - 1.76% (1.22) in the Melitide® group and - 1.59% (1.31) in the Victoza® group. The upper limit of the 95% one-sided confidence interval (CI) of the mean difference between Melitide® and Victoza® in lowering HbA1C was lower than the predefined margin (mean difference - 0.18, 95% CI - 0.5 to 0.15). Similar findings were obtained with the intention-to-treat analysis. No statistically significant differences were observed between the two study arms regarding the proportion of patients achieving HbA1C < 7% (p = 0.210), other efficacy parameters (p > 0.05), and reported adverse events (p = 0.916). Furthermore, none of the patients developed anti-liraglutide antibodies. CONCLUSION: The biosimilar liraglutide (Melitide®) was noninferior in efficacy and comparable in safety when compared with the reference liraglutide. TRIAL REGISTRATION: NCT03421119.

A randomized controlled trial for evaluating an occupational therapy self management intervention in adults with type 2 diabetes.

This study evaluated the efficacy of the Occupational Therapy Diabetes Self-Management intervention (OTDSM) to enhance glycemic stability and self-management skills in people with diabetes type-2. Based on this single-blind randomized trial, 30 subjects with diabetes type-2 were assigned to two groups of intervention and control. The intervention group received a 10-week program, consisting of four group visits and six individualized sessions. The control group received an individual session and three weekly phone calls. The primary study outcome, blood hemoglobin A1C, was measured before and three months after the study. The secondary outcome was assessed in terms of the participants' self-management behaviors, self-efficacy, diabetes distress, depressive symptoms, and performance and satisfaction with daily activities. These outcomes were evaluated three times: before, one month into, and three months after the study. The study findings demonstrated significant differences between the two groups in the hemoglobin A1C levels, self-management behaviors, self-efficacy, and performance and satisfaction with daily routines after the intervention (P < 0.05). No significant differences existed between the groups for the extent of diabetes distress and depressive symptoms. Inclusion of occupational therapy protocol into the plan of care for people with diabetes can improve health outcomes by promoting their routine participation in self-management activities.

Visceral Adipose Tissue and Non-alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes.

AIM: To explore the association of visceral adipose tissue (VAT) area and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study comprising 100 patients with T2DM and 100 non-T2DM individuals, matched for age, sex, and body mass index (BMI). Transient elastography was used to assess hepatic steatosis and liver stiffness measurements (LSM). Controlled attenuation parameter (CAP) was used to quantify hepatic steatosis. To distinguish grades of hepatic steatosis, cutoff values were as follows: S1 ≥ 302, S2 ≥ 331, and S3 ≥ 337 dB/m. Moreover, VAT area was measured by dual-energy X-ray absorptiometry in accordance with validated protocols. RESULTS: CAP score was significantly higher in participants with T2DM (294.61 ± 3.82 vs. 269.86 ± 3.86 dB/ m; P < 0.001). Furthermore, 42% of participants with T2DM had hepatic steatosis (S > S1: 302 dB/m), while this figure was 26% in non-T2DM group (P < 0.003). The mean liver stiffness measurement was also significantly higher in patients with T2DM (5.53 vs. 4.79 kPa; P < 0.001). VAT area was greater in patients with T2DM compared to non-T2DM individuals: 163.79 ± 47.98 cm2 versus 147.49 ± 39.09 cm2, P = 0.009. However, total and truncal fat mass were not different between the two groups. Age, BMI, waist circumference, ALT, CAP, and LSM were significantly associated with VAT area. BMI and VAT area were the important determinants of steatosis in both groups of participants with and without T2DM. Moreover, the VAT area was associated with the severity of hepatic steatosis and liver stiffness, independent of anthropometric measures of obesity. CONCLUSION: VAT area is a major determinant of the severity of hepatic steatosis and liver stiffness in patient with T2DM.

Type 2 diabetes: patient assessment of chronic illness care.

OBJECTIVE: We tried to assess perception of chronic illness care in people with type 2 diabetes and to determine whether demographic variables, self-care behavior, as well as affective variables were related with perception of chronic illness care. METHODS: We conducted a secondary analysis of the previously published cross-sectional study in 441 Iranian people with type 2 diabetes. Chronic illness care was assessed with the validated tool of patient assessment of chronic illness care (PACIC). Different aspects of care according to the chronic care model are measured on a scale of 1-5, with 5 being highest perception of care. The association between perception of chronic illness care and measured variables were tested using spearman correlation test as well as univariate and multiple linear regression analysis. RESULTS: Finally, 380 filled out the PACIC questionnaire, completely (53.4% female, mean age: 54.73 ± 8.0 years, mean PACIC score: 2.52 ± 0.87). In spearman correlation test, considering PACIC score as the dependent variable, chronic illness care was inversely associated with level of education and distress, whereas, insulin treatment, wellbeing, family-social support and self-management were positively associated with chronic care (All p value<0.05). In the multiple linear regression analysis, family-social support was positively related to chronic care while level of education, marital status, diabetes-related distress, and high density lipoprotein had significant negative relationship with PACIC score (All p value<0.05). CONCLUSIONS: Family-social support, level of education, marital status, and diabetes-related distress are the major determinants of patient experience of chronic illness care in people with type 2 diabetes.

Personalization of health information prescription in diabetes clinical setting: A qualitative study.

BACKGROUND: The prevalence of diabetes makes considerable costs for health-care organizations. The increase of patient's self-care abilities by use of personalizing health information prescription can reduce these costs. This study was conducted to explore the benefits and challenges related to personalizing health information prescription in diabetes clinical settings. MATERIALS AND METHODS: The samples included diabetes education officials working in specialized diabetes clinics and Diabetes Research Centre managers of Iran and Tehran Universities of Medical Sciences. They were 21 cases and selected through purposeful sampling method. Semi-structured interview and focus discussion groups were used to collect the viewpoints of specialists. Interview guide, based on literature review and the documents of diabetes, was used in interviews and focus groups. Their validity was affirmed by specialists. The interview texts were coded in MAXQDA10 software and analyzed through content analysis method. RESULTS: The most important benefits of personalizing health information prescription were classified into five themes as follows: medical services improvement, facilitation of consumers to information resources, improvement in patients' knowledge and awareness, increase in self-care ability and disease management, reinforcing the relation between physician and patient and keeping physician in the information prescription cycle. The challenges of personalizing of health information prescription were revealed as follows: Recognition of patients' personal characteristics at the turn of entering the system, systems' functional modifiers especially bilateral interaction and relation to patient's health file, content recognition, and creating suitable protocol. CONCLUSION: This study showed that diabetes clinical settings face different organizational and process challenges for establishing the personalization of health information prescription. The most important challenges which should be considered in designing information prescription in diabetes clinical environments are as follows: reinforcing physicians' recognition of information prescription benefits, lack of integrative electronic health information system, and patient primary assessment in the first stage of entering the patient into the system in respect of clinical and personal aspects in information needs of consumer.

Hepatic Steatosis and Fibrosis in Type 2 Diabetes: A Risk-Based Approach to Targeted Screening.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common in people with type 2 diabetes mellitus (T2DM). We aimed to explore predictive factors of NAFLD in T2DM and identify high risk subgroups. METHODS: This was a cross-sectional study including 100 individuals with T2DM and 100 without diabetes matched for age, sex, and body mass index (BMI). Hepatic steatosis grades (calculated by controlled attenuation parameters-CAP score-3), and liver fibrosis stages (F0-F4) were determined using transient elastography. RESULTS: The frequency of NAFLD was comparable between the two study groups. However, CAP scores were significantly higher in individuals with diabetes (294.90 ± 53.12 vs. 269.78 ± 45.05 dB/m; P < 0.001). Fifty percent of individuals with diabetes had severe steatosis (S3), while this figure was 31.6% in those without diabetes (P < 0.05). Significant fibrosis (F2-F4) was more frequent in individuals with T2DM (13% vs. 4.1%, P = 0.02). Individuals with T2DM and advanced fibrosis had significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and CAP score compared to those without fibrosis (P < 0.05). In the regression analysis, a model including BMI, WHR, AST and female gender explained 50% of the variation in CAP score in patients with diabetes (all P < 0.05, adjusted R2 : 0.508). CAP scores were also the major determinant of liver fibrosis in this group (OR: 1.04; CI: 1.017-1.063; P = 0.001). CONCLUSION: Individuals with diabetes are more likely to have severe fibrosis. Obesity (especially central obesity), the female gender, elevated liver enzymes, and higher degree of insulin resistance are associated with more advanced liver disease in individuals with T2DM.

The Association between Presence of Comorbidities and COVID-19 Severity: A Systematic Review and Meta-Analysis.

AIM: Several studies reported the accompaniment of severe COVID-19 with comorbidities. However, there is not a systematic evaluation of all aspects of this association. Therefore, this meta-analysis aimed to assess the association between all underlying comorbidities in COVID-19 infection severity. METHODS: Electronic literature search was performed via scientific search engines. After the removal of duplicates and selection of articles of interest, 28 studies were included. A fixed-effects model was used; however, if heterogeneity was high (I2 > 50%) a random-effects model was applied to combine the data. RESULTS: A total of 6,270 individuals were assessed (1,615 severe and 4,655 non-severe patients). The median age was 63 (95% confidence interval [CI]: 49-74) and 47 (95% CI: 19-63) years in the severe and non-severe groups, respectively. Moreover, about 41% of patients had comorbidities. Severity was higher in patients with a history of cerebrovascular disease: OR 4.85 (95% CI: 3.11-7.57). The odds of being in a severe group increase by 4.81 (95% CI: 3.43-6.74) for a history of cardiovascular disease (CVD). This was 4.19 (95% CI: 2.84-6.19) for chronic lung disease and 3.18, 95% CI: 2.09-4.82 for cancer. The odds ratios of diabetes and hypertension were 2.61 (95% CI: 2.02-3.3) and 2.37 (95% CI: 1.80-3.13), respectively. CONCLUSIONS: The presence of comorbidities is associated with severity of COVID-19 infection. The strongest association was observed for cerebrovascular disease, followed by CVD, chronic lung disease, cancer, diabetes, and hypertension.

COVID-19: Case fatality and ACE2 inhibitors treatment concerns in patients with comorbidities.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in patients with associated comorbidities. These RNA viruses containing 4 structural proteins usually use spike protein to enter the host cell. Angiotensin-converting enzyme 2 (ACE2) acts as a host receptor for the virus. Therefore, medications acting on renin-angiotensin-aldosterone system can lead to serious complications, especially in patients with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

Gait stability of diabetic patients is altered with the rigid rocker shoes.

BACKGROUND: Rigid-rocker shoes may induce gait instability in diabetics, however, this is not clearly investigated. The present study investigates if rigid-rocker shoes influence diabetic gait stability. METHODS: Fourteen non-neuropathic and nine neuropathic diabetics, plus eleven healthy young-adults were recruited. Full-body kinematic data was captured during walking. Experimental conditions included barefoot and three rocker-shoe designs according to the rocker angle, apex angle and apex position (R10: 10°, 80°, 60%; R15: 15°, 95°, 52%; R20: 20°, 95°, 60%). Sagittal and frontal stability margin, plus fear of fall were main outcome measures. FINDINGS: Sagittal stability margin was not affected by health, however, was increased with R10 and R15 in non-neuropathic diabetics and healthy individuals (R2 = 0.16). Variability of sagittal stability margin was not altered in neuropathic diabetics, but was increased with R15 and R20 in healthy participants, with R15 in non-neuropathic diabetics (R2 = 0.12). Frontal stability margin (R2 = 0.46) and its variability (R2 = 0.39) were significantly increased in neuropathic and non-neuropathic diabetics compared to healthy individuals. Frontal stability margin was significantly higher with R15 in neuropathic diabetics, and with R20 in both non-neuropathic and healthy participants. Sagittal and frontal stability margin were strongly correlated with fear of fall in neuropathic diabetics. INTERPRETATIONS: R15 and R20 might challenge gait stability of diabetics cause them restrict centre of mass motion thereby imposing a tighter control over walking. However, neuropathic diabetics generally walk very cautious due to neuropathy and increased fear of fall. Frontal stability margin, highly affected by health and experimental condition, is a more sensitive indicator of gait stability.

The Effect of Bariatric Surgery on Peripheral Polyneuropathy: a Systematic Review and Meta-analysis.

Neurological complications such as peripheral neuropathies are the most common complications among patients with morbid obesity following bariatric surgery. Reduction in nutrient intake especially thiamin may develop polyneuropathy, while neuropathic symptoms improved in patients with diabetes independent of glycemic control after bariatric surgery. The aim of the present review is to investigate the effect of bariatric surgery on peripheral neuropathy. Electronic literature search was done via scientific search engines. After the removal of duplicates and selection of articles of interest, 4 studies were included. A random effects model was applied in this meta-analysis. Considering the pooled analysis, bariatric surgery was significantly associated with Neuropathy Symptoms Score (NSS) (ES = - 3.393, 95% CI (- 4.507, - 2.278), and P value < 0.0001). Reduction in NSS for patients with type 2 diabetes and BMI < 35 kg/m2 who were insulin-dependent was more than patients with morbid obesity without diabetes. Furthermore, neuropathy disability score (NDS) significantly decreased in patients having bariatric surgery (ES = - 0.626, 95% CI (- 1.120, - 0.132), and P value < 0.013). The NDS significantly decreased in patients with type 2 diabetes and BMI < 35 kg/m2 treated with insulin as well as patients with morbid obesity and type 2 diabetes. In subgroup of patients with follow-up of more than 6 months after surgery, a significant reduction in NDS was detected while this reduction was not significant in patients with a follow-up of 6 months or less. Bariatric surgery had a positive effect on peripheral neuropathy, though many studies showed neuropathy as one of the complications of bariatric surgery.

Evaluation of all Types of Metabolic Bariatric Surgery and its Consequences: a Systematic Review and Meta-Analysis.

BACKGROUND: Considering conflicting results on the consequences of all types of obesity surgery, we were to summarize them via a systematic review. METHODS: Electronic literature search was done via scientific search engines. After the removal of duplicates and selection of articles of interest, 771 studies were included. RESULTS: Insulin resistance indicators were significantly improved after bariatric surgery. Leptin was also significantly decreased while adiponectin was significantly increased. Although the level of metabolic hormones changed after bariatric surgery, they were not statistically significant. Inflammation indicators were significantly decreased. Significant reduction was also detected in PAI-1 and sICAM-1. CONCLUSIONS: Bariatric surgery is beneficial in morbidly obese patients. Although treating obesity in a surgical way may cause some complications, the weight loss is generally safe and effective.

Predictors of Glycemic Response and Change in HbA1c Following Newly Initiated Basal Insulin Among Insulin Naïve Adults With Type 2 Diabetes.

This sub-analysis of the Iran-AFECT study was to determine the baseline characteristics are predicting the likelihood of attainment of HbA1c goal and changing in HbA1c after initiation of basal insulin glargine in insulin naïve people with type 2 diabetes not adequately controlled with oral glucose-lowering drugs. Iran-AFECT was a 24-week, prospective, multicenter, observational study of people with type 2 diabetes initiated or switched to insulin glargine. In this sub-analysis, we included all insulin naïve people. Glycemic response was defined as HbA1c≤7.0% and/or change in HbA1c at week 24. Data on 433 participants were included. The mean HbA1c was 8.9%±0.9% at baseline which decreased to 7.6%±1.2% (P<0.001). By week 24, 36% of the participants reached HbA1c≤7.0%. In univariate analysis, the strongest association was for the baseline HbA1c (r2=0.32, P<0.001). In multivariate analysis, predictors of change in HbA1c were baseline HbA1c (r2=0.29, P<0.001), and dosing of glargine (r2=0.01, P=0.02). The baseline HbA1c was accounting for 88% of explainable variances in HbA1c. The best cut-off predicting glycemic response for baseline HbA1c was 8.5%. Among factors predicting response to initiating basal insulin therapy with insulin glargine, baseline HbA1c is the strongest predictor explaining most of the variances in HbA1c change.

The challenge of living with diabetes in women and younger adults: A structural equation model.

BACKGROUND: Attitudes toward diabetes care are different between genders and age-groups. Furthermore, diabetes related challenges may cause psychosocial problems. Therefore, we were to compare the psychosocial status and glycemic control in women and men with type 2 diabetes (T2D) in different age-groups. METHODS: 441 adults with T2D were recruited. Demographic, self-care behavior, resources and affective variables as well as the health related quality of life (HRQoL) were measured. The median age of 55 was used as the cut-off for the age comparison. Structured equation modeling (SEM) investigated the relationship between age, gender, psychosocial factors and glycemic control. RESULTS: Finally, 203 women and 177 men completed the study (86.1%). There was no significant difference in mean duration of T2D, or glycemic control between genders or age-groups. Women, especially those below the median age of 55, had significantly higher level of diabetes-related distress (2.16±0.94 vs. 1.92±0.81), depression (9.67±5.37 vs. 7.54±5.06), and anxiety (19.81±12.04 vs. 12.81±9.04, P<0.05 for all comparisons), while people above the age of 55 reported better self-management and patient-physician relationship. HRQoL was lower in women compared to men (0.77±0.23 vs. 0.81±0.18, P=0.02). The final SEM suggested that the effect (standardized ß coefficient) of gender and age on affective variables was 0.25 and -0.19 (P<0.05), respectively, though psychosocial factors did not directly influence HbA1c. CONCLUSIONS: This study shows that psychosocial factors are associated with age and gender in patients with T2D; with younger women demonstrating higher level of depressive symptoms, anxiety, and diabetes-related distress independent of status of glycemic control.

Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study.

BACKGROUND: The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). METHODS: It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. RESULTS: HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. CONCLUSIONS: Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.

Type 2 Diabetes: Model of Factors Associated with Glycemic Control.

OBJECTIVES: The purpose of this study was to evaluate the related factors and their intercorrelated impacts on glycemic control in people with type 2 diabetes mellitus. METHODS: Patients with type 2 diabetes were recruited for this study during their regular clinic visits at a major medical centre in Iran. Glycated hemoglobin (A1C) levels were used as the indicator of glycemic control. Regression analysis was used to determine the relationships between glycemic control and demographics, self-care behaviours, resources and affective variables. Moreover, the associations between diabetes-related distress and measured variables were tested. RESULTS: Three hundred eighty people with type 2 diabetes completed the study. The mean duration of diabetes was 8.94±6.57 years, and the mean A1C levels were 7.78%±1.7%. Diabetes-related distress was significantly associated with A1C levels, controlling for all other variables (p=0.01). On the other hand, depression (p<0.001), self-management (p<0.001), anxiety (p<0.001) and patient-physician relationship (p=0.023) were significantly associated with diabetes-related distress. CONCLUSIONS: Diabetes-related distress was found to be associated with glycemic control in people with type 2 diabetes, whereas age, depression, anxiety, self-management and family and social support may affect glycemic control indirectly through diabetes-related distress. Thus, it is important to assess and, if appropriate, treat people with diabetes for diabetes-related distress in order to identify and help them overcome barriers to optimal glycemic control.

Morphine Suppository versus Indomethacin Suppository in the Management of Renal Colic: Randomized Clinical Trial.

Background. Renal colic is a medical emergency due to the rapid onset and devastating nature of its pain. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are both used as first-line choices in its management. Aim. This study aimed to compare the efficacy and safety of opioids and NSAIDs in the management of acute renal colic. Methods. One hundred and fifty-eight patients were divided into two groups (n = 79) and received either 10 mg morphine or 100 mg indomethacin suppositories. The severity of pain was measured using verbal numeric rating scale at baseline and 20, 40, 60, and 90 minutes after the administration of analgesics. Drug side effects as well as patients' vital signs were also recorded. Results. The mean decrease in the pain score during the first 20 minutes was significantly higher among those who received morphine suppository. However, no significant difference was observed between the two groups regarding the mean decrease in pain score during the first 40, 60, and 90 minutes after the admission. Prevalence of drug side effects or changes in the vital signs was not significantly different between the two groups. Conclusions. Morphine suppositories seem to be more efficient in achieving rapid pain relief comparing to indomethacin.

Hypoglycemia: Adverse Cardiovascular Outcomes in Non-Critically Ill People with Type 2 Diabetes.

BACKGROUND: Hypoglycemia is associated with adverse health outcomes and can result in vascular events in diabetic patients. The impact of hypoglycemia on cardiovascular outcomes in non-critically ill people with diabetes is not well-determined. So, we examined short-term cardiovascular outcomes of hypoglycemic events in people with type 2 diabetes treated with insulin during routine clinical care. METHODS: This study was conducted in Tehran, Iran from January 2012 to January 2013. One hundred and twenty non-critically ill people with type 2 diabetes on oral glucose lowering drugs were enrolled. Insulin therapy was initiated for uncontrolled diabetes. The patients were educated to perform self-monitoring of blood glucose on a daily basis. Furthermore, they were asked to record the results if they experienced any symptom indicative of hypoglycemia during the 24 weeks of the study. The occurrence of any major cardiovascular event including unstable angina, fatal or non-fatal myocardial infarction, fatal and non-fatal stroke, or death from cardiovascular cause was also evaluated based on the patients' hospital records. RESULTS: There were 210 hypoglycemic episodes and 31 major cardiovascular events. Forty four percent of patients with documented hypoglycemic episodes developed cardiovascular events compared to 15.6% of those who did not experience any hypoglycemia (P = 0.001). The odds ratio for occurrence of major cardiovascular events related to hypoglycemia was 7.41 (CI = 2.15-25.47) with a risk ratio of 2.66. CONCLUSION: Hypoglycemia is a major risk factor for occurrence of the first major cardiovascular event in non-critically ill people with type 2 diabetes initiating insulin therapy.

General Practitioners' Knowledge and Clinical Practice in Management of People with Type 2 Diabetes in Iran; The Impact of Continuous Medical Education Programs.

BACKGROUND: To obtain information related to the knowledge and clinical practice of general practitioners (GPs) in management of people with type 2 diabetes, and to explore the impact of formal continuous medical education (CME) programs. METHODS: A total of 1104 GPs participated in a cross sectional survey related to diabetes management considering ADA/EASD consensus 2011 focused on demographic and background characteristics, diabetes related knowledge, and patient care. Fisher's Exact and Chi-square tests were used in the analysis of contingency tables. RESULTS: The majority of the participants (83.9%) worked in large cities and 39.8% had taken part in CME programs in diabetes management. Overall, 52% of the GPs knew the treatment goal for HbA1c. The rate was slightly higher for those taken part in CME (P = 0.003). Considering patient care, slightly more than half of the participants answered correctly to the questions on duration and distribution of physical activity, with no difference by taking part in CME programs. On average, 41.5% of the physicians selected metformin as the first OGLD for treatment of type 2 diabetes, and only 27.9% stated that they add basal insulin to OGLD if treatment failed. CONCLUSION: The results of this study provide the evidence that the knowledge and clinical practice of Iranian GPs in management of type 2 diabetes were not satisfactory. Furthermore, traditional CME programs in diabetes management were not effective in changing the GPs' clinical practice. Consequently, designing and implementing more effective strategies are necessary for improving patient health related outcomes.