Oenanthe Javanica Extract Protects Against Experimentally Induced Ischemic Neuronal Damage via its Antioxidant Effects

Background:

Water dropwort (Oenanthe javanica) as a popular traditional medicine in Asia shows various biological properties including antioxidant activity. In this study, we firstly examined the neuroprotective effect of Oenanthe javanica extract (OJE) in the hippocampal cornus ammonis 1 region (CA1 region) of the gerbil subjected to transient cerebral ischemia.

Methods:

Gerbils were established by the occlusion of common carotid arteries for 5 min. The neuroprotective effect of OJE was estimated by cresyl violet staining. In addition, 4 antioxidants (copper, zinc superoxide dismutase [SOD], manganese SOD, catalase, and glutathione peroxidase) immunoreactivities were investigated by immunohistochemistry.

Results:

Pyramidal neurons in the CA1 region showed neuronal death at 5 days postischemia; at this point in time, all antioxidants immunoreactivities disappeared in CA1 pyramidal neurons and showed in many nonpyramidal cells. Treatment with 200 mg/kg, not 100 mg/kg, OJE protected CA1 pyramidal neurons from ischemic damage. In addition, 200 mg/kg OJE treatment increased or maintained antioxidants immunoreactivities. Especially, among the antioxidants, glutathione peroxidase immunoreactivity was effectively increased in the CA1 pyramidal neurons of the OJE-treated sham-operated and ischemia-operated groups.

Conclusion:

Our present results indicate that treatment with OJE can protect neurons from transient ischemic damage and that the neuroprotective effect may be closely associated with increased or maintained intracellular antioxidant enzymes by OJE.     

Predictors of major lower limb amputation among type II diabetic patients admitted for diabetic foot problems

INTRODUCTION

Diabetes mellitus (DM) is the most common cause of amputations in Malaysia. This study aimed to identify the predictive factors for major lower limb amputation among patients with type 2 DM (T2DM) who were admitted to a hospital, in order to reduce its likelihood.

METHODS

This cross-sectional study involved 218 patients with T2DM who were admitted to Hospital Tengku Ampuan Afzan, Kuantan, Malaysia, for diabetic foot problems from June 2011 to July 2012. A form was developed to document the patients’ profiles, comorbidities, complications, investigations, treatment and clinical outcomes. The predictors for major lower limb amputations were determined using univariate and stepwise logistic regression analysis.

RESULTS

A total of 31 patients underwent major lower limb amputations (25 transtibial, 6 transfemoral). The following factors were found to be associated with the incidence of major lower limb amputations: T2DM duration ≥ 10 years, diabetic neuropathy, diabetic nephropathy, presentation with gangrene, diabetic foot conditions of Wagner grade 4 or 5, and necrotising fasciitis. Patients who underwent major amputations had significantly lower haemoglobin and albumin levels, and higher total white blood cell counts, erythrocyte sedimentation rates, and C-reactive protein, urea and creatinine levels. However, only T2DM duration ≥ 10 years, positive bacterial culture and albumin levels were significant on stepwise logistic regression analysis.

CONCLUSION

T2DM duration ≥ 10 years, positive bacterial culture and low albumin levels were found to be significant predictive factors for major lower limb amputation among patients with T2DM admitted for diabetic foot problems.     

Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus

Objective:

To evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.

Data Sources:

A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: “ZnT8,” “type 1 diabetes,” “latent autoimmune diabetes in adults,” “type 2 diabetes,” “islet autoantibodies,” “zinc supplement,” “T cells,” “β cell,” “immune therapy.” We also searched the reference lists of selected articles.

Study Selection:

English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.

Results:

The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.

Conclusions:

ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.     

Association between urinary 8-OHdG and pulse wave velocity in hypertensive patients with type 2 diabetes mellitus

INTRODUCTION

Oxidative stress, assessed using 8-hydroxy-2’-deoxyguanosine (8-OHdG), can be associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HT). We investigated the correlation between urinary 8-OHdG and pulse wave velocity (PWV) in hypertensive and non-hypertensive T2DM patients with fair glycaemic control to determine the clinical significance of HT as a comorbidity in the diabetic state.

METHODS

Clinical data, including traditional cardiovascular risk factors, diabetic complications, prescribed agents, urinary 8-OHdG level and brachial-ankle PWV, was collected from T2DM patients with and without HT.

RESULTS

There were 76 patients (45 men, 31 women; mean age 61 years; mean haemoglobin A1c level 6.5%) in the study cohort. T2DM patients with HT had significantly higher mean PWV than patients without HT (1,597 cm/s vs 1,442 cm/s; p < 0.05). Patients with HT showed no significant difference in 8-OHdG levels relative to those without HT (median 7.9 ng/mg creatinine vs 8.8 ng/mg creatinine; p > 0.05). Simple linear correlation and stepwise multiple linear regression analyses revealed that 8-OHdG levels correlated independently, significantly and positively with PWV among T2DM patients with HT (r = 0.33, p < 0.05; β = 0.23, p < 0.05). No significant correlation was observed between 8-OHdG levels and PWV among T2DM patients without HT.

CONCLUSION

In the hypertensive state, oxidative stress can be responsible for the development of arterial stiffness, even in patients with fairly well controlled T2DM. Oxidative stress management may be necessary for the prevention of cardiovascular disease in this population.     

Clinical profile and outcomes of adult patients with hyperglycemic emergencies managed at a tertiary care hospital in Nigeria

Background:

To document the clinical profile and treatment outcomes of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) managed in a tertiary care hospital.

Materials and Methods:

This was a retrospective review of hospital records of patients with DKA and HHS admitted to a tertiary care hospital over a 24-month period. Data on demographics, precipitating factors, clinical features, serum electrolytes, duration of hospital admission, and mortality were extracted.

Results:

Eighty-four patients were included in the study. Fifty (59.5%) were females. Ten (11.9%) persons had type 1 diabetes mellitus (T1DM) and 74 (88.1%) had type 2 diabetes mellitus (T2DM). There were 35 cases of DKA and 49 cases of HHS. Nine patients with T1DM presented in DKA and one in HHS. Forty-eight (55.2%) subjects were previously not diagnosed of diabetes mellitus (DM). The mean±SEM age, casual blood glucose, calculated serum osmolality, and duration of hospital stay of the study subjects were 50.59±1.63 years, 517.98±11.69 mg/dL, 313.59±1.62 mOsmol/L, and 18.85±1.78 days, respectively. Patients with T2DM were significantly older than those with T1DM (54.32±1.34 vs. 23.40±1.38 years, P<0.001).The precipitating factors were poor drug compliance 23 (27.4%), malaria 12 (14.3), urinary tract infection 10 (11.9%), lobar pneumonia 4 (4.8%), and unidentifiable in 29 (34.5%). Common electrolyte derangements were hyponatremia, 31 (36.9%) and hypokalemia 21 (25%). Mortality rate was 3.6%.

Conclusion:

DKA is common in patients with T2DM.Over 50% of the patients presenting with DKA or HHS have no previous diagnosis of DM. Non-compliance, malaria, and infections are important precipitants. Mortality rate is low.     

Glycemic control,complications, and associated autoimmune diseases in children and adolescents with type 1 diabetes in Jeddah,Saudi Arabia

Objectives:

To investigate the relationship between metabolic control, acute and long-term complications, the coexistence of autoimmune diseases, and to assess the different factors that can affect the glycemic control level among children with type 1 diabetes mellitus (T1DM).

Methods:

This is a cross-sectional study that included 228 T1DM children and adolescents visiting the pediatric diabetes clinic at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from January 2013 to January 2014. The clinical and laboratory characteristics of the patients were recorded. Metabolic control, complications, and associated autoimmune diseases were evaluated.

Results:

The mean age of patients was 10.99 years, and the glycated hemoglobin (HbA1c) level was 8.8%. Acute complications included ketoacidosis in 65.4% of patients, and hypoglycemic attacks in 68.9%. Long-term complications were detected in patients including retinopathy (4.4%), microalbuminuria (16.2%), and dyslipidemia (8.3%). Autoimmune thyroiditis was noted in 14%, and celiac disease was found in 19.7% of patients. A significant difference was found in pubertal and pre-pubertal age groups in terms of glycemic control (p=0.01).

Conclusion:

The level of HbA1c was found to be higher among the pubertal age group. A relationship between autoimmune diseases and gender was determined.Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in pediatric patients. The incidence of T1DM among children is rising worldwide, and varies depending on different factors. The overall annual increase is estimated at 3% with approximately 70,000 children worldwide expected to develop T1DM every year.1 In Saudi Arabia, the reported prevalence in children and adolescents was 109.5/100000 in 2008.2 Type 1 diabetes mellitus is an autoimmune disease characterized by insulin deficiency due to destruction of pancreatic beta cells. Patients with T1DM are at high risk of developing other autoimmune diseases, such as autoimmune thyroiditis (AIT) and celiac disease (CD).3,4 Moreover, T1DM can lead to numerous complications in pediatric patients, with the most common acute complications including hypoglycemia, and diabetes ketoacidosis (DKA). Long-term complications in childhood include retinopathy, nephropathy, and dyslipidemia, among others. In this study, we aimed to assess the relationships between glycemic control, acute and long-term complications, associated autoimmune diseases,and to assess other different factors that can affect or predict the glycemic control level among children with T1DM visiting the pediatric diabetes clinic at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia.     

Association of body mass index and abdominal adiposity with atherogenic lipid profile in Nigerians with type 2 diabetes and/or hypertension

Background:

We explored the relationship between anthropometric indices (obesity and abdominal adiposity) and the presence of an atherogenic lipid profile in Nigerians with major cardiovascular risk factors (type 2 diabetes mellitus-T2DM, hypertension-HBP, and concomitant disease).

Materials and Methods:

Using a prospective design, 278 patients with T2DM, HBP, or concomitant disease, attending out-patient diabetes and hypertension clinics at a tertiary institution in Nigeria were evaluated. All patients were cholesterol-lowering oral medication naοve. Demographic and clinical data and anthropometric measurements were documented. Fasting lipid profiles were measured in all cases. The cut-off points for defining dyslipidaemia were: Elevated total cholesterol (TC) (mg/dL) ≥200, elevated low-density lipoprotein cholestrol (LDL-C) (mg/dL) ≥100, low high-density lipoprotein cholesterol (HDL-C) (mg/dL) <40 for men and <50 for women, and high triglycerides (TG) (mg/dL) ≥150 mg/dL.

Results:

We found a significantly higher mean BMI (kg/m²) in the HBP group (30.5 ± 6.0) compared to T2DM (28.1 ± 5.9) and concomitant HBP and T2DM groups (29.4 ± 5.2) (ANOVA; P = 0.02). The most frequent dyslipidaemia was elevated LDL-C in 92 (96.8%) HBP, 73 (85.9%) T2DM and 79 (80.6%) concomitant disease. The frequency of low HDL-C was highest in T2DM (68.2%) compared to the other 2 groups (P = 0.03).

Conclusions:

Only TG levels were found to relate with any anthropometric index (waist circumference (WC) in this case) in Nigerians with major cardiovascular risk factors in this study. Routine anthropometric indices do not appear to be reliable surrogates for atherogenicity measured by abnormalities in TC, LDL-C and HDL-C.     

A comparative drug utilisation study of the treatment of diabetes in Malaysia and Australia

Background

Once a disease of developed countries, type 2 diabetes mellitus (T2DM) has become widespread worldwide. For people with T2DM, achievement of therapeutic outcomes demands the rational and quality use of medicine.

Aims

The primary aim of this study was to examine the prevalence of diabetes and prescribing patterns of anti-diabetic medications in Australia and Malaysia.

Methods

The most recent, publicly available, statistical reports (2004–2008) on the use of medicines published in Australia and in Malaysia were evaluated. Defined daily doses (DDDs/1,000 population/day) were derived from the reports and used to rank and compare individual drug use.

Results

There was an increasing trend in the prevalence of diabetes in Australia, although there is a greater predicted increase in prevalence for Malaysia. While drugs used for the treatment of diabetes were not the most highly used drugs in Australia, their use increased during the study period, from 42.64 to 48.61 DDD/1,000/day. Anti-diabetic drugs were the most frequently dispensed class of drugs in Malaysia. Although the total consumption of anti-diabetic drugs in Malaysia decreased between 2006 and 2007 (from 40.30 to 39.72), this was followed by a marked increase to 46.69 in 2008. There was a marked reduction in the dispensing of insulin in Malaysia from 2004 to 2007 (7.77 to 3.23).

Conclusion

The use of drugs to treat diabetes does not reflect the usage patterns found in Australia. Effective drug use reviews are required to ensure impartial access in middle- and low-income countries.     

Initiating Characteristics of Early-onset Type 2 Diabetes Mellitus in Chinese Patients

Background:

Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.

Methods:

This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level.

Results:

In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37–4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47–38.03), dyslipidemia (OR 2.65, CI 1.54–4.56), diastolic blood pressure (OR 1.02, CI 1.00–1.04), and body mass index (OR 0.95, CI 0.92–0.99) are independent factors for early-onset T2DM.

Conclusions:

We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.     

The association of cardiovascular disease with impaired health-related quality of life among patients with type 2 diabetes mellitus

INTRODUCTION

The aim of this study was to evaluate the health-related quality of life (HRQoL) of Malaysian patients with type 2 diabetes mellitus (T2DM) who have cardiovascular disease (CVD), as well as identify the determinants of HRQoL among this cohort of patients.

METHODS

This study was an analytical cross-sectional study involving 313 patients aged 30–78 years (150 men, 163 women; mean age 55.7 ± 9.2 years) who were diagnosed with T2DM (mean duration of T2DM 10.1 ± 8.1 years) at two tertiary Malaysian government hospitals. The patients’ sociodemographic, lifestyle, clinical and laboratory data were collected prospectively from medical records and via face-to-face interviews. HRQoL was assessed using the 15D instrument – a generic, 15-dimensional and standardised measure of HRQoL that can be used as both a profile and a single index score measure.

RESULTS

T2DM patients with CVD were found to have significantly lower 15D HRQoL scores than their non-CVD counterparts (p < 0.001). The HRQoL of T2DM patients with CVD was significantly lower than those without CVD (p < 0.05) in all of the 15 dimensions of the 15D instrument. Multinomial logistic regression analysis using backward stepwise method revealed a significant association between CVD and impaired HRQoL (odds ratio [OR] 11.746, 95% confidence interval [CI] 4.898–28.167). Age (OR 1.095, 95% CI 1.054–1.137), duration of T2DM (OR 1.085, 95% CI 1.032–1.140), ethnicity (OR 0.411, 95% CI 0.187–0.903), body mass index (OR 1.074, 95% CI 1.006–1.148), and physical activity level (OR 3.506, 95% CI 1.415–8.689) were also significant predictors of HRQoL.

CONCLUSION

In T2DM patients, the presence of CVD was significantly associated with a lower HRQoL. Therefore, the importance of tertiary prevention to minimise the potential deterioration of the HRQoL of T2DM patients with CVD should be highly emphasised.     

The prevalence of albuminuria among diabetic patients in a primary care setting in Singapore

INTRODUCTION

Microalbuminuria is an early sign of kidney damage. The prevalence of microalbuminuria in Singapore has been reported to be 36.0%–48.5%. However, the prevalence of microalbuminuria reported in these studies was determined with one urine sample using a qualitative urine test. The aim of this study was to determine the prevalence of micro- and macroalbuminuria using a more stringent criterion of two positive quantitative urine albumin-creatinine ratio (ACR) tests.

METHODS

We conducted a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) who were followed up at a primary care clinic in Singapore. Patients were diagnosed to have albuminuria if they had two positive ACR tests within a seven-month period.

RESULTS

A total of 786 patients with T2DM met the study’s inclusion criteria. 55.7% were already on an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB). The prevalence rates of micro- and macroalbuminuria were 14.2% and 5.7%, respectively. Patients with albuminuria were more likely to have hypertension (odds ratio [OR] 3.47, 95% confidence interval [CI] 1.55–7.80). Diabetics with poorer diabetic control (OR 1.88, 95% CI 1.26–2.79), and higher systolic (OR 1.69, 95% CI 1.14–2.49) and diastolic (OR 1.96, 95% CI, 1.20 to 3.22) blood pressures were more likely to have albuminuria.

CONCLUSION

In the present study, the prevalence of microalbuminuria is significantly lower than that previously reported in Singapore. The presence of hypertension, poor diabetic control and suboptimal blood pressure control are possible risk factors for albuminuria in patients with T2DM.     

Affection of Single-Nucleotide Polymorphisms in miR-27a,miR-124a,and miR-146a on Susceptibility to Type 2 Diabetes Mellitus in Chinese Han People

Background:

Polymorphisms of microRNA (miRNA), as a novel mechanism, are closely associated with disease states by interfering with miRNA function. Direct correlations have been identified between single-nucleotide polymorphisms (SNPs) in miRNA, but the effect on type 2 diabetes mellitus (T2DM) onset among Chinese population remains unclear. Therefore, the aim of this study was to identify correlations between common SNPs in miR-27a, miR-146a, and miR-124a with T2DM among a Chinese population, as well as to explore diabetic pathological mechanisms and the impact of environmental factors.

Methods:

SNPscan technology was used to genotype 995 patients newly diagnosed with T2DM and 967 controls. Logistic regression analysis was performed to compare mutation frequencies between cases and controls.

Results:

We found no significant correlations between all genotypes of these miRNAs and T2DM in our research. However, stratification analysis identified a lower risk of T2DM associated with the rs531564GC genotype among younger subjects (age < 45 years) (adjusted P = 0.043; odds ratio [OR] = 0.73; 95% confidence interval [CI] = 0.54–0.99). Furthermore, the rs895819CC genotype in overweight people (24 ≤ body mass index [BMI] < 28) was significantly associated with an increased risk of T2DM (adjusted P = 0.042; OR = 1.73; 95% CI = 1.02–2.94), while the rs2910164 genotype in miR-146a was not significantly correlated with T2DM. The genetic risk score was calculated based on the number of risk alleles of the three SNPs and was found to be correlated to total cholesterol (adjusted P = 0.021).

Conclusions:

The rs531564GC genotype acted as a protective factor to decrease the risk of T2DM in younger subjects (age < 45 years), while the presence of the rs895819CC genotype increased the risk of illness among overweight subjects (24 ≤ BMI < 28 kg/m²). The presence of SNPs in miRNA might promote disease by affecting miRNA expression and gene function. Thus, miRNA mimics or inhibitors that directly regulate miRNA expression present novel and promising therapeutic targets.     

Effects of 12-month, 2000IU/day vitamin D supplementation on treatment na?ve and vitamin D deficient Saudi type 2 diabetic patients

Objectives:

To determine whether 12-month, 2000IU/day vitamin D supplementation cardiometabolically improves treatment naïve type 2 diabetes mellitus (T2DM) Saudi patients with vitamin D deficiency.

Methods:

This 12-month interventional study was conducted at primary health centers in 5 different residential areas in Riyadh, Saudi Arabia between January 2013 and January 2014. Forty-five Saudi T2DM patients were enrolled. Baseline anthropometrics, glycemic, and lipid profiles were measured and repeated after 6 and 12 months. All subjects were provided with 2000IU vitamin D supplements for one year.

Results:

Vitamin D deficiency at baseline was 46.7%, 31.8% after 6 months, and 35.6% after 12 months, indicating an overall improvement in the vitamin D status in the entire cohort. Insulin and homeostatic model assessment-insulin resistance (HOMA-IR) after 12 months were significantly lower than a 6 months (p<0.05), but comparable to baseline values. Mean levels of triglycerides increased overtime from baseline (1.9±0.01 mmol/l) to 12 months (2.1±0.2 mmol). This modest increase in serum triglycerides was parallel to the insignificant decrease in circulating high-density lipoprotein -cholesterol levels.

Conclusion:

Twelve-month vitamin D supplementation of 2000IU per day in a cohort of treatment naïve Saudi patients with T2DM resulted in improvement of several cardiometabolic parameters including systolic blood pressure, insulin, and HOMA-IR. Further studies that include a placebo group are suggested to reinforce findings.Diabetes mellitus (DM) is a major public health problem worldwide. The population of people with DM is on the rise secondary to an aging and urbanized population as well as an increasing prevalence of risk factors such as obesity and physical inactivity.1 In the Kingdom of Saudi Arabia (KSA) alone, the most-recent age-adjusted prevalence of type 2 diabetes mellitus (T2DM) was reported to be 31.6% in adults, considered among the highest in the Gulf region.2 Type 2 diabetes mellitus among Saudis results from the interaction between a genetic predisposition, behavioral, and environmental risk factors, which can manifest as early as pre-teens.3 This is alarming since the long-term cost of diabetes can be crippling to any health care system as there are many associated health problems, including: increased risk of coronary heart disease, eye problems, nerve damage, foot, and kidney problems.4 Vitamin D insufficiency, defined as serum 25-hydroxyvitamin D levels <50 nmol/l (25-OH-D), is also common in patients with T2DM.5 Using this arbitrary definition, it has been estimated that one billion people worldwide have either vitamin D deficiency or insufficiency.6 In KSA, there is an abundance of local literature pointing to an increased prevalence of vitamin D deficiency.7,8 Taken together, current evidence suggests a link between vitamin D deficiency and progression of T2DM, but results are not consistent and therefore the beneficial effects of vitamin D correction among T2DM patients with vitamin D deficiency remains controversial.9,10 Given that patients with T2DM are at higher risk for cardiometabolic complications, this study aims to determine whether vitamin D status improvement through dietary means improves the cardiometabolic profile of treatment naïve T2DM Saudi patients with vitamin D deficiency.     

Myopia in young patients with type 1 diabetes mellitus

INTRODUCTION

This study aimed to evaluate the proportion of young patients with type 1 diabetes mellitus (T1DM) who have myopia, as well as the risk factors associated with myopia in this group.

METHODS

In this cross-sectional study, patients aged < 21 years with T1DM for ≥ 1 year underwent a comprehensive eye examination. Presence of parental myopia, and average hours of near-work and outdoor activity were estimated using a questionnaire. Annualised glycosylated haemoglobin (HbA1c), defined as the mean of the last three HbA1c readings taken over the last year, was calculated. Multivariate analysis using genetic, environmental and diabetes-related factors was done to evaluate risk factors associated with myopia.

RESULTS

Of the 146 patients (mean age 12.5 ± 3.6 years) recruited, 66.4% were Chinese and 57.5% were female. Myopia (i.e. spherical equivalent [SE] of –0.50 D or worse) was present in 96 (65.8%) patients. The proportion of patients with myopia increased from 25.0% and 53.6% in those aged < 7.0 years and 7.0–9.9 years, respectively, to 59.2% and 78.4% in those aged 10.0–11.9 years and ≥ 12.0 years, respectively. Higher levels of SE were associated with lower parental myopia (p = 0.024) and higher annualised HbA1c (p = 0.011).

CONCLUSION

Compared to the background population, the proportion of myopia in young patients with T1DM was higher in those aged < 10 years but similar in the older age group. Myopia was associated with a history of parental myopia. Environmental risk factors and poor glycaemic control were not related to higher myopia risk.     

Prevalence of diabetes mellitus and impaired fasting blood glucose in patients with Lichen Planus

Background

The relationship between Lichen Planus (LP) and diabetes was studied previously, but the results were in conflict. The aim of this study was to find the prevalence of diabetes mellitus (DM) in patients with LP among Iranian patients.

Methods

In this study, 80 patients with LP were enrolled. They referred to dermatology clinic of our hospital during one year. A self-designed checklist for the study included duration of the disease, the pattern of the distribution of lichenoid lesions and fasting blood sugar (FBS).

Results

From 80 patients with LP, 16 (20%) had diabetes. Also, 14 patients (17.5%) had impaired fasting glucose. The mean age of diabetic patients was significantly higher than non-diabetic group (p=0.039). In addition, the duration of LP in patients with DM was significantly higher than non-diabetic patients (p=0.024).

Conclusion

In our study, we saw a high prevalence of DM among patients with LP. Comparing our findings with the overall prevalence of DM in Iran, there was a significant difference between the prevalence of DM among patients with LP and the overall prevalence (p=0.001). Regarding our findings screening for FBS in patients with LP is required in Iran.     

Effect of Continuous Positive Airway Pressure Therapy on Glycemic Excursions and Insulin Sensitivity in Patients with Obstructive Sleep Apnea-hypopnea Syndrome and Type 2 Diabetes

Background:

For patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and type 2 diabetes mellitus (T2DM), the night sleep interruption and intermittent hypoxia due to apnea or hypopnea may induce glycemic excursions and reduce insulin sensitivity. This study aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy in patients with OSAHS and T2DM.

Methods:

Continuous glucose monitoring system (CGMS) was used in 40 patients with T2DM and newly diagnosed OSAHS. The measurements were repeated after 30 days of CPAP treatment. Subsequently, insulin sensitivity and glycohemoglobin (HbA1c) were measured and compared to the pretreatment data.

Results:

After CPAP therapy, the CGMS indicators showed that the 24-h mean blood glucose (MBG) and the night time MBG were significantly reduced (P < 0.05 and P = 0.03, respectively). The mean ambulatory glucose excursions (MAGEs) and the mean of daily differences were also significantly reduced (P < 0.05 and P = 0.002, respectively) compared to pretreatment levels. During the night, MAGE also significantly decreased (P = 0.049). The differences between the highest and lowest levels of blood glucose over 24 h and during the night were significantly lower than prior to CPAP treatment (P < 0.05 and P = 0.024, respectively). The 24 h and night time durations of high blood glucose (>7.8 mmol/L and > 11.1 mmol/L) decreased (P < 0.05 and P < 0.05, respectively) after the treatment. In addition, HbA1c levels were also lower than those before treatment (P < 0.05), and the homeostasis model assessment index of insulin resistance was also significantly lower than before CPAP treatment (P = 0.034).

Conclusions:

CPAP therapy may have a beneficial effect on improving not only blood glucose but also upon insulin sensitivity in T2DM patients with OSAHS. This suggests that CPAP may be an effective treatment for T2DM in addition to intensive diabetes management.     

Impaired secretion of glucagon-like peptide 1 during oral glucose tolerance test in patients with newly diagnosed type 2 diabetes mellitus

Objectives:

To assess glucagon-like peptide 1 (GLP-1) secretion after oral glucose tolerance tests (OGTTs) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) to clarify changes in GLP-1 secretion during the course of T2DM.

Methods:

In this cross sectional study, 80 subjects were divided into the NGT, IGT, and T2DM groups after undergoing a 75 g OGTT from March to December 2014 at the School of Medicine, First Affiliated Hospital, Shihezi University, Xinjiang, China. Plasma total GLP-1 was measured at 0, 30, 60, 120, and 180 minutes. Homeostasis model assessment of insulin resistance (HOMA-IR), islet β-cell function (HOMA-β), Gutt index, Matsuda index, incremental GLP-1 (ΔGLP-1), and areas under the curves of GLP-1 (AUC_glp-1), glucose (AUC_g), and insulin (AUC_ins) were calculated.

Results:

Plasma total GLP-1 at 30-120 minutes and ΔGLP-1 at 30-120 minutes were lower in the T2DM group than in the IGT and NGT groups (p<0.05). Peak GLP-1 levels were 35% lower in the T2DM group than in the NGT group. Plasma total GLP-1, ΔGLP-1, and AUC_glp-1 correlated negatively with HOMA-IR and AUC_g, and positively with HOMA-β, Gutt index, Matsuda index, and AUC_ins (p<0.05).

Conclusion:

The GLP-1 secretion after 75 g OGTT was impaired in newly diagnosed T2DM patients, inversely proportional to IR and hyperglycemia, and positively correlated with β-cell function and insulin sensitivity.Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with multiple pathophysiological abnormalities. Currently, T2DM is one of the most common chronic diseases in almost every country. China has the largest population of diabetes patients. The prevalence of diabetes among adults in China is 11.6%, which is equivalent to 114 million patients.1 Glucagon-like peptide-1 (GLP-1) is secreted by L-cells in the distal parts of the intestines in response to nutrient ingestion.2 The GLP-1 regulates blood glucose levels deriving from several mechanisms. It stimulates insulin secretion from the pancreatic β-cells in a glucose-dependent manner and suppresses glucagon secretion.3,4 The GLP-1 also affects gastrointestinal motility, enhances satiety, promotes weight loss, and increases β-cell mass.5-9 Therefore, impaired GLP-1 secretion may contribute to the initiation and development of DM. As a consequence of these properties, GLP-1 based therapies (GLP-1 agonists and dipeptidyl peptidase-4 inhibitors) are currently playing a cornerstone role in the treatment of T2DM. Since GLP-1 plays an important role in the pathophysiology of DM, the assessment of GLP-1 secretory responses in individuals with different glycometabolism states is of great interest. The outcomes of GLP-1 secretion after the administration of an oral glucose load in individuals with and without diabetes are controversial. Toft-Nielsen et al10 reported a 53% reduction in integrated incremental GLP-1 concentrations in T2DM patients relative to healthy controls, while participants with impaired glucose tolerance (IGT) had an intermediate GLP-1 response. However, other studies11,12 have reported that GLP-1 secretion was not reduced in response to an oral glucose tolerance test (OGTT), or meal test in patients with T2DM. The mode of GLP-1 secretion in Asians may be different. Thus far, limited data are available on comparisons of GLP-1 levels among Chinese individuals with newly diagnosed T2DM, IGT, and normal glucose tolerance (NGT). Therefore, this study was conducted to measure GLP-1 levels during a standard OGTT in Chinese subjects with newly diagnosed T2DM, IGT, and NGT, in order to characterize the changes in GLP-1 secretion during the course of T2DM development. We also investigated the relationship between GLP-1 secretion, insulin resistance (IR), and insulin β-cell function.     

Insulin therapy refusal among type II diabetes mellitus patients in Kubang Pasu district,Kedah, Malaysia

INTRODUCTION

Diabetes mellitus is a rising non-communicable disease in Malaysia. Insulin therapy refusal is a challenge for healthcare providers, as it results in delayed insulin initiation. This study was conducted to determine the prevalence of insulin therapy refusal and its associated factors.

METHODS

This cross-sectional study was conducted at seven public health clinics in Kubang Pasu district of Kedah, Malaysia, from March to October 2012. A newly developed and validated questionnaire was used and participants were selected via systematic random sampling. Only patients diagnosed with type II diabetes mellitus (T2DM) and under the public health clinic care in Kubang Pasu were included in the study. Multiple logistic regression was used to study the association between insulin therapy refusal and its associated factors.

RESULTS

There were 461 respondents and the response rate was 100%. Among these 461 patients with T2DM, 74.2% refused insulin therapy. The most common reason given for refusal was a lack of confidence in insulin injection (85.4%). Multiple logistic regression revealed that respondents who had secondary education were 55.0% less likely to refuse insulin therapy than those who had primary education or no formal education (adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25–0.82, p = 0.009). There was also a significant inverse association between glycated haemoglobin (HbA1c) level and insulin therapy refusal (adjusted OR 0.87, 95% CI 0.76–1.00, p = 0.047).

CONCLUSION

Insulin therapy refusal is common in Kubang Pasu. Educational status and HbA1c level should be taken into consideration when counselling patients on insulin therapy initiation.     

Lack of association between the insulin receptor substrates-1 Gly972Arg polymorphism and type-2 diabetes mellitus among Saudis from Eastern Saudi Arabia

Objectives:

To investigate the association between the insulin receptor substrate-1 (IRS1) Gly972Arg polymorphism and type-2 diabetes mellitus (T2DM) among Saudis from Eastern Saudi Arabia.

Methods:

This study was conducted between May and December 2014 at King Fahad Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia. In a case-control study design, a total of 143 subjects (age range: 35-73 years) comprising 74 healthy controls and 69 patients with T2DM were examined. Blood samples were collected from subjects and subjected to genomic DNA extraction and chemical analysis. The IRS1 Gly972Arg polymorphism was then genotyped using the standard polymerase chain reaction-restriction fragment length polymorphism technique.

Results:

Eight out of 74 (10.8%) of the control group carried at least one copy of the mutated allele. The frequency (8.7%) of the IRS1 variant was also found in the diabetic group. Logistic regression analysis showed an adjusted odds ratio of 1.04, 95% confidence interval 0.28 - 3.95, and a p-value of 0.94.

Conclusion:

We failed to find any association between the IRS1 Gly972Arg polymorphism and T2DM.Diabetes mellitus (DM) is a major medical and public health concern worldwide. In 2014, it has been estimated that there were 382 million sufferers of diabetes worldwide.1 The prevalence of diabetes in Saudi Arabia is 23.9%, which is among the highest in the gulf area and the world.1,2 Type-2 diabetes mellitus (T2DM) represents approximately 90-95% of all diabetes cases.3 Type-2 diabetes mellitus is characterized by high blood glucose due to the inability of body cells to respond to insulin, a phenomenon known as insulin resistance.4 The genetic factors behind the insulin resistance are not well-understood and are under intensive research. Insulin is a metabolically important peptide hormone secreted from ß-cells of the pancreas in response to high blood glucose. Insulin signaling starts with binding of the insulin molecule to its cognate membrane insulin receptor (IR). This binding triggers conformational changes in the juxtamembrane intracellular region of the receptor causing autophosphorylation of certain tyrosine residues. The activated receptor then phosphorylates and activates a family of intracellular effector proteins known as insulin receptor substrates 1 to 4 (IRS-1 to 4).5 These activated proteins then interact with the regulatory subunit (p85) of the enzyme phosphatidylinositol (PI) 3-kinase causing glucose transporter-4 (Glut-4) translocation to the cell membrane to increase glucose uptake.6 In this signaling pathway, IRS1 seems to play a major role as suggested by IRS1 knockout mice studies.7 Additionally, several polymorphisms in the IRS1 gene were associated with insulin resistance, obesity, and T2DM.8,9 The single nucleotide polymorphism (SNP) (rs1801278) in the IRS1 gene causing an amino acid substitution where glycine (GGG) is replaced by arginine (AGG) at codon 972 was first described by Almind et al.10 It is the most widely studied candidate of the IRS1 gene variants by testing its association with insulin resistance and T2DM.11 However, the association of this polymorphism with the development of T2DM has not been consistent around the world. In a study focusing on Mexican participants, Burguete-Garcia et al8 found that the IRS1 Gly972Arg variant was significantly associated with T2DM. Another study that also focused on Mexican population similarly found a significant association between Gly972Arg variant and genetic susceptibility to T2DM.12 A study on Indian population from Hyderabad also reported significant association with T2DM.13 A meta-analysis study conducted in 2009 of 30 studies had shown that there was no significant association between the IRS1 Gly972Arg variant and T2DM.11 In addition, previous studies also reported no association between the IRS1 Gly972Arg polymorphism and T2DM.14-18 There is no report on the frequency of this polymorphism and its association with T2DM in the Eastern Province of Saudi Arabia. Thus, the aim of the current work is to examine the association between the IRS1 Gly972Arg polymorphism with T2DM among Saudis.     

Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice

Background:

Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system and noninfectious immune responses. It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion (I/R) injury. However, the role of TLR4 in the process of I/R injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is still unknown. In this study, we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.

Methods:

A model of potassium-induced CA was performed on TLR4-mutant mice (C3H/HeJ) and wild-type mice (C3H/HeN). After 3 min of untreated CA, resuscitation was attempted with chest compression, ventilation, and intravenous epinephrine. Behavioral tests were performed on mice on day 3 after CPR. The morphological changes in hippocampal neurons were assessed by light and electron microscopy. Expressions of TLR4 and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blot. Levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were measured with enzyme-linked immunosorbent assay (ELISA).

Results:

On day 3 after resuscitation the overall mortality was 33.33% in C3H/HeJ group compared with 53.33% in C3H/HeN group (P < 0.05). And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test (P < 0.05). Meanwhile, the percentage of nonviable neurons was 21.16% in C3H/HeJ group compared with 53.11% in C3H/HeN group (P < 0.05). And there were significantly lower levels of hippocampal TNF-α and MPO in C3H/HeJ mice (TNF-α: 6.85±1.19 ng/mL, MPO: 0.33±0.11 U/g) than C3H/HeN mice (TNF-α: 11.36±2.12 ng/mL, MPO: 0.54±0.17 U/g) (all P < 0.01). CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group. However, the expression of ICAM-1 was much lower in C3H/HeJ group than in C3H/HeN group after CPR (P < 0.01).

Conclusion:

TLR4 signaling is involved in brain damage and in inflammation triggered by CA/CPR.