The relationship between glycaemic control and mortality in patients with type 2 diabetes in general practice (ZODIAC-11)

Background

The relationship between the degree of glycaemic control and mortality remains an important topic of discussion.

Aim

This study aimed to investigate this relationship.

Design of study

Prospective cohort study.

Setting

Primary care.

Method

A total of 1145 patients with type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) in 1998. Their survival status was recorded in September 2004. Mortality ratios were calculated using standardised mortality ratios (SMRs). Associations between haemoglobin A_1c (HbA_1c) levels and mortality were studied with a Cox proportional hazard model. HbA_1c levels were studied as continuous and as categorical variables.

Results

A total of 335 patients died after a median follow-up period of 5.8 years. The SMR (95% confidence interval [CI]) for total mortality was 1.86 (95% CI = 1.66 to 2.06) and 2.24 (95% CI = 1.91 to 2.61) for cardiovascular mortality. For each 1% increase in HbA_1c there was a 21% increase in the hazard ratio for total mortality. When compared with the target HbA_1c group (HbA_1c 6.5–7%), the group with very poor glycaemic control (HbA1c >9%) had a hazard ratio of 2.21 (95% CI = 1.42 to 3.42) for total mortality. The group with normal glycaemic control (HbA_1c <6.5%) had a hazard ratio of 1.00 (95% CI = 0.46 to 2.19) for total mortality.

Conclusion

HbA_1c level was associated with mortality and this effect seemed largely attributable to patients who were in really poor glycaemic control. The absence of differences in mortality in the groups with lower HbA_1c levels supports the position that there is no basis for continually decreasing the therapeutic target HbA_1c level in patients with type 2 diabetes mellitus.     

Feasibility of a mobile phone-based data service for functional insulin treatment of type 1 diabetes mellitus patients

Background

Patients with type 1 diabetes mellitus (DM1) have to be active participants in their treatment because they are inevitably responsible for their own day-to-day-care. Availability of mobile Internet access is advancing rapidly and mobile phones are now widely available at low cost. Thus, mobile phones have the potential to assist in daily diabetes management and to enable a telemedical interaction between patients and health care professionals.

Objective

The aim of the study was to evaluate the feasibility and user acceptance of a mobile phone–based data service to assist DM1 patients on intensive insulin treatment.

Methods

A software application called Diab-Memory (based on Java 2 Mobile Edition) has been developed to support patients when entering diabetes-related data with synchronization to the remote database at the monitoring center. The data were then processed to generate statistics and trends, which were provided for the patient and his/her health care professional via a Web portal. The system has been evaluated in the course of a clinical before-after pilot trial. Outcome measures focused on patients’ adherence to the therapy, availability of the monitoring system, and the effects on metabolic status. General user acceptance of the system was evaluated using a questionnaire.

Results

Ten patients (four female) with DM1 participated in the trial. Mean age was 36.6 years (± 11.0 years) and prestudy glycated hemoglobin (HbA_1c) was 7.9% (± 1.1%). A total of 3850 log-ins were registered during the 3 months of the study. The total number of received datasets was 13003, which equates to an average of 14 transmitted parameters per patient per day. The service was well accepted by the patients (no dropouts), and data transmission via mobile phone was successful on the first attempt in 96.5% of cases. Upon completion of the study, a statistically significant improvement in metabolic control was observed (HbA_1c: prestudy 7.9% ± 1.1% versus poststudy 7.5% ± 0.9%;P= .02). While there was a slight decrease in average blood glucose level (prestudy 141.8 mg/dL ± 22.5 mg/dL vs poststudy 141.2 mg/dL ± 23.1 mg/dL;P= .69), the difference was not statistically significant.

Conclusion

The results of the clinical pilot trial indicate that this proposed diabetes management system was well accepted by the patients and practical for daily usage. Thus, using the mobile phone as patient terminal seems to provide a ubiquitous, easy-to-use, and cost efficient solution for patient-centered data acquisition in the management of DM1. To confirm the promising results of the pilot trial further research has to be done to study long-term effects on glycemic control and cost-effectiveness.     

Taiwanese female vegetarians have lower lipoprotein-associated phospholipase A2 compared with omnivores

Purpose

Many studies supported that vegetarians have a lower risk of cardiac diseases and mortality, partly due to better blood pressure and serum cholesterol profiles. However, the inflammatory markers, especially lipoprotein-associated phospholipase A2 (Lp-PLA2), have not been well-studied. This study aimed to compare inflammatory markers and conventional risk factors between vegetarians and omnivores.

Materials and Methods

One hundred and seventy-three vegetarians and 190 omnivores were studied. Fasting blood samples were obtained to compare levels of glucose, total cholesterol, triacylglycerol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, homocysteine, Lp-PLA2 activity, and high-sensitivity C-reactive protein (hs-CRP).

Results

Vegetarians had higher serum levels of the following markers: hs-CRP (1.8 ± 3.4 vs. 1.2 1.8 mg/L, respectively; p = 0.05), homocysteine (9.39 ± 3.22 vs. 7.62 ± 2.41 µmol/L, respectively; p < 0.01), and triacylglycerol (96.91 ± 59.56 vs. 84.66 ± 43.24 mg/dL, respectively; p < 0.05). Vegetarians also had lower levels of Lp-PLA2 (18.32 ± 7.19 10-3 µmol/min/mL vs. 20.22 8.13 10-3 µmol/min/mL; p < 0.05), total cholesterol (180.62 ± 36.55 mg/dL vs. 192.73 ± 36.57 mg/dL; p < 0.01), LDL cholesterol (118.15 ± 32.8 vs. 126.41 ± 34.28 mg/dL; p < 0.05), and HDL cholesterol (55.59 ± 13.30 vs. 62.09 ± 14.52 mg/dL, p < 0.01). Multivariate analyses demonstrated that a vegetarian diet increases the chances for high serum hs-CRP and low Lp-PLA2 activity.

Conclusion

In addition to lower total cholesterol, LDL-cholesterol, and HDL-cholesterol, Taiwanese female vegetarians have lower serum Lp-PLA2 activity but higher levels of hs-CRP, homocysteine, and triacylglyerol. It might be due to geographic differences of vegetarian diets, and further studies are needed.     

Antidiabetic effect of kolaviron,a biflavonoid complex isolated from Garcinia kola seeds,in Wistar rats

Background

Hypoglycaemic effect of kolaviron (KV), (biflavonoid from Garcinia kola) in streptozotocin (STZ)-diabetic rats has been established.

Objectives

To evaluate the possible protective effects of KV on cardiac, renal and hepatic tissues of STZ-diabetic rats.

Methods

This study consists of four groups of 6 rats each. Groups one and two contained non-diabetic and untreated-diabetic rats, respectively. Groups three and four were made up of KV- and glibenclamide (GB) - treated diabetic rats, respectively.

Results

STZ-intoxication caused a significant (p<0.05) increase in the relative weight of liver in diabetic rats. STZ-diabetic rats had significant increase (p<0.05) in the levels of fasting blood glucose (FBG), á-amylase and HbA_1c. A marked and significant (p<0.05) increase in the levels of cardiac, renal and liver marker indices such as serum creatine kinase, lactate dehydrogenase, creatinine, urea and alanine aminotransferase were observed in untreated diabetic rats. Also, untreated diabetic rats had significantly (p<0.05) elevated urinary glucose and protein and, lowered creatinine clearance. In KV- and GB- treated groups, the levels of FBG, á-amylase and HbA_1c were significantly (p<0.05) reduced, while treatment with KV significantly (p<0.05) attenuated the cardiac, renal and liver marker indices.

Conclusion

KV offered significant antidiabetic and tissues protective effects in the rats.     

Patient characteristics correlated with quality indicator outcomes in diabetes care

Background

Quality indicators were adopted to compare quality of care across health systems.

Aim

To evaluate whether patient characteristics influence primary care physicians'' diabetes quality indicators.

Design of study

Retrospective cohort study.

Setting

Primary care setting.

Method

The study was conducted in the Central District of Clalit Health Service in Israel. The five measures of diabetes follow-up were: the percentage of patients with diabetes for whom glycosylated haemoglobin (HbA_1c), microalbumin, low-density lipoprotein (LDL)-cholesterol, and blood pressure were measured at least once, and the percentage of patients who were seen by an ophthalmologist, during 2005. Three outcome measures were chosen: the percentage of patients with diabetes and HbA_1c <7 mg%, the percentage of patients with diabetes and blood pressure <130/80 mmHg, and the percentage of patients with diabetes and LDL-cholesterol <100 mg/dl in 2005. Sociodemographic information was retrieved about all the physicians'' patients with diabetes.

Results

One-hundred and seventy primary care physicians took care of 18 316 patients with diabetes. The average number of patients with diabetes per physician was 107 (range 10–203). A lower quality indicator score for HbA_1c <7 mg% was correlated with a higher percentage of patients of low socioeconomic status (P<0.001) and new immigrants (P = 0.002), and correlated with borderline significance with higher mean patients'' body mass index (P = 0.024); lower quality indicator score for blood pressure <130/80 mmHg was related to higher patients'' age (P = 0.006). None of the diabetes follow-up measures were related to patients'' characteristics.

Conclusion

Achieving good glycaemic control is dependent on patient characteristics. New immigrants, patients of low socioeconomic status, and older patients need special attention to avoid disparities.     

Matrix metalloproteinases in type 2 diabetes and non-diabetic controls: effects of short-term and chronic hyperglycaemia

Introduction

The role of matrix metalloproteinases (MMPs) in type 2 diabetes mellitus (DM) is not clear as increased activation of MMPs in the vasculature contrasts with decreased activity of MMPs in the kidneys, contributing to development of nephropathy.

Material and methods

We measured serum MMP-2 and MMP-9 in 22 subjects with type 2 DM age (mean ± SD) 56.7 ±16.8 years, BMI 31.8 ±4.6 kg/m², HbA_1c 8.45 ±1.78% and in 32 controls, age 39.2 ±16.0 years, BMI 35.2 ±8.5 kg/m². In 15 subjects with 2 DM we also measured MMP-2 and MMP-9 at discharge from hospital and after 3 months (n = 8). In controls, MMP-2 and -9 were also measured during 75 g oral glucose tolerance test (OGTT).

Results

Concentrations of MMP-2 and MMP-9 were lower in subjects with type 2 DM (219 ±62 ng/ml vs. 305 ±63 ng/ml and 716 ±469 ng/ml vs. 1285 ±470 ng/ml, for MMP-2 and MMP-9, respectively, p < 0.05). MMP-9 concentrations fell at 120 min of OGTT from 1675 ±372 ng/ml to 1276 ±422 ng/ml (p < 0.05). In diabetic subjects there was a correlation between MMP-9 and HbA_1c (r = 0.51, p< 0.05). In subjects with diabetes there was a fall of HbA_1c from 9.77 ±1.76% to 8.36 ±1.54% (p < 0.01), at three months post-discharge. There was no difference in MMP-2, but there was a fall in MMP-9 at three months post-discharge in comparison to concentrations observed at admission (854 ±560 ng/ml vs. 500 ±235 ng/ml, p= 0.02).

Conclusions

Matrix metalloproteinases in type 2 and MMP-9 concentrations were lower in subjects with 2 DM than in non-diabetic controls. Regulation of MMPs appears to be complex as hyperglycaemia during OGTT results in a decrease in MMP-9, while chronic hyperglycaemia, reflected by HbA_1c, correlates with MMP-9 concentrations in subjects with 2 DM.     

Serum vascular endothelial growth factor and angiopoietin-2 are associated with the severity of systemic inflammation rather than the presence of hemoptysis in patients with inflammatory lung disease

Purpose

Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases.

Materials and Methods

We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009.

Results

The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO₂) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels

Conclusion

Our study suggests that serum VEGF and Ang-2 levels are associated with PaO₂ and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.     

A more appropriate cardiac troponin T level that can predict outcomes in end-stage renal disease patients with acute coronary syndrome

Purpose

Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS).

Materials and Methods

Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis.

Results

AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p<0.001; 95% CI, 0.95-1.00). The summation of sensitivity and specificity was highest at the initial cTnT value of 0.35 ng/mL (sensitivity, 0.95; specificity, 0.97). Survival analysis showed a statistically significant difference in all-cause and cardiovascular mortalities for the group with an initial cTnT ≥0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality.

Conclusion

Because ESRD patients with an initial cTnT concentration ≥0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are ≥0.35 ng/mL.     

The role of oxidative stress and antioxidants in the pathogenesis of age-related macular degeneration

OBJECTIVE:

To investigate the role of oxidant/antioxidant status and protein oxidation in the development of age-related macular degeneration.

METHOD:

The activities of serum superoxide dismutase and glutathione peroxidase and the levels of serum malondialdehyde, advanced oxidation protein products, glutathione and vitamin C were measured in 25 patients with age-related macular degeneration and 25 control subjects without age-related macular degeneration.

RESULT:

The malondialdehyde and advanced oxidation protein product levels in the serum were significantly higher in the age-related macular degeneration patient group than in the control group (p<0.05). The superoxide dismutase activity in the serum was significantly lower in the age-related macular degeneration patient group than in the control group (p<0.05). The levels of vitamin C and glutathione and the activity of glutathione peroxidase in the serum were unchanged between groups (p>0.05).

CONCLUSION:

The results of the present study suggest that decreased effectiveness of the antioxidant defense system and increased oxidative stress may play a role in the pathogenesis of age-related macular degeneration.     

The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine

OBJECTIVES:

Hyperuricemia is a risk factor for contrast-induced acute kidney injury in patients with chronic kidney disease. This study evaluated the value of hyperuricemia for predicting the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine who were undergoing percutaneous coronary interventions.

METHODS AND RESULTS:

A total of 788 patients with relatively normal baseline serum creatinine (<1.5 mg/dL) undergoing percutaneous coronary intervention were prospectively enrolled and divided into a hyperuricemic group (n = 211) and a normouricemic group (n = 577). Hyperuricemia is defined as a serum uric acid level>7 mg/dL in males and >6 mg/dL in females. The incidence of contrast-induced acute kidney injury was significantly higher in the hyperuricemic group than in the normouricemic group (8.1% vs. 1.4%, p<0.001). In-hospital mortality and the need for renal replacement therapy were significantly higher in the hyperuricemic group. According to a multivariate analysis (adjusting for potential confounding factors) the odds ratio for contrast-induced acute kidney injury in the hyperuricemic group was 5.38 (95% confidence interval, 1.99-14.58; p = 0.001) compared with the normouricemic group. The other risk factors for contrast-induced acute kidney injury included age >75 years, emergent percutaneous coronary intervention, diuretic usage and the need for an intra-aortic balloon pump.

CONCLUSION:

Hyperuricemia was significantly associated with the risk of contrast-induced acute kidney injury in patients with relatively normal serum creatinine after percutaneous coronary interventions. This observation will help to generate hypotheses for further prospective trials examining the effect of uric acid-lowering therapies for preventing contrast-induced acute kidney injury.     

Stress responses of neonates related to maternal characteristics

Purpose

To investigate the pre- and post-heelstick stress response patterns of infants and to identify related maternal factors.

Materials and Methods

Fifty-two mothers and their 57 infants were studied. Stress response patterns in neonates were collected by measurements of pulse rate, oxygen saturation, and salivary cortisol. Maternal demographic factors and awakening saliva were collected.

Results

Median level of pulse rate of infant increased from 132.1 to 140.4 beats per minute and salivary cortisol was elevated from 0.41 µg/dL to 0.70 µg/dL during the periods of discomfort, while oxygen saturation decreased from 97% to 95%. Infant''s pulse rate change was negatively correlated with gestational age (GA) (r = - 0.37, p < 0.05), whereas the change of infants'' salivary cortisol was correlated positively with maternal age (r = 0.29, p < 0.05). GA was the only independently significant predictor of pulse rate responses (R² = 0.15, p < 0.05). Influence of maternal age on infants'' salivary cortisol changes (R² = 0.09, p < 0.05) was observed in a stepwise multiple regression.

Conclusion

These findings suggest that maternal age and gestational period can be influential factors for stress responses in infants. Therefore, it would be important to consider the demographic characteristics of mother-infant pairs to evaluate these influential factors.     

Differences between the Measured and Calculated Free Serum Phenytoin Concentrations in Epileptic Patients

Purpose

The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients who receive phenytoin. Because most of the phenytoin in serum is bound to proteins, the level of serum albumin influences the amount of free phenytoin.

Materials and Methods

We compared the measured and calculated free phenytoin levels in epileptic patients who were taking phenytoin monotherapy, using the Sheiner-Tozer equation. A total of 49 patients (30 men and 19 women; age range, 15 - 87 years) were included in the study and their trough serum phenytoin and albumin concentrations were analyzed.

Results

The linear correlation between free and total phenytoin concentrations was moderate (r = 0.822, p < 0.001). The mean difference between measured and calculated free phenytoin was large (0.65 ± 0.88 µg/mL; 95% confidence interval (CI), -1.11 to 2.41). After dividing the patients into groups by albumin concentration, hypoalbuminemic patients (< 3.5 g/dL) more often had a greater percent difference (≥ 20%) than observed in the normoalbuminemic (≥ 3.5 g/dL) group.

Conclusion

In hypoalbuminemic patients, the measurement of free phenytoin level is necessary to properly evaluate the phenytoin level than that calculated from total phenytoin level.     

Residual C-peptide in patients with Type 1 diabetes and multiethnic backgrounds

OBJECTIVE:

To evaluate serum C-peptide in 88 patients from a multiethnic population with Type-1 diabetes and variable disease durations.

METHOD:

Eighty-eight patients with a mean disease duration of 8.1±7.6 years were included and underwent C-peptide measurement before and after glucagon stimulation. Chi-squared and Mann Whitney U-tests were used to compare the variables between groups (all two-tailed, α  = 0.05). Spearmańs correlation coefficient was used to test the association between the continuous variables. Logistic regression was used for the multivariate analysis. Twenty-eight (31.8%) individuals had significantly detectable C-peptide levels after stimuli, particularly those with a shorter disease duration (p<0.001).

RESULTS:

Patients with detectable C-peptide levels required lower insulin doses (p<0.009) and had similar HbA1C results (p = 0.182) and fewer chronic complications (p = 0.029).

CONCLUSION:

C-peptide detection was common in Type-1 diabetics, particularly shortly after being diagnosed. This result may have clinical implications.     

Screening for Cushing��s Syndrome in Obese Patients

OBJECTIVES:

The aim of this study was to examine the frequency of Cushing’s syndrome (CS) in obese patients devoid of specific clinical symptoms of Cushing’s syndrome.

METHODS:

A total of 150 obese patients (129 female, 21 male; mean age 44.41 ± 13.34 yr; mean BMI 35.76 ± 7.13) were included in the study. As a first screening step, we measured 24-h urinary free cortisol (UFC). An overnight 1-mg dexamethasone suppression test was also performed on all patients. Urinary free cortisol levels above 100 μg/24 h were considered to be abnormal. Suppression of serum cortisol <1.8 μg/dL after administration of 1 mg dexamethasone was the cut-off point for normal suppression. The suppression of the serum cortisol levels failed in all of the patients.

RESULTS:

Measured laboratory values were as follows: ACTH, median level 28 pg/ml, interquartile range (IQR) 14–59 pg/ml; fasting glucose, 100 (91–113) mg/dL; insulin, 15.7 (7.57–24.45) mU/ml; fT₄, 1.17 (1.05–1.4) ng/dL; TSH, 1.70 (0.91–2.90) mIU/L; total cholesterol, 209 (170.5–250) mg/dL; LDL-c, 136 (97.7–163) mg/dL; HDL-c, 44 (37.25–50.75) mg/dL; VLDL-c, 24 (17–36) mg/dL; triglycerides, 120.5 (86–165) mg/dL. The median UFC level of the patients was 30 μg/24 h (IQR 16–103). High levels of UFC (>100 μg/24 h) were recorded in 37 patients (24%). Cushing’s syndrome was diagnosed in 14 of the 150 patients (9.33%). Etiologic reasons for Cushing’s syndrome were pituitary microadenoma (9 patients), adrenocortical adenoma (3 patients), and adrenocortical carcinoma (1 patient).

CONCLUSION:

A significant proportion (9.33%) of patients with simple obesity were found to have Cushing’s syndrome. These findings argue that obese patients should be routinely screened for Cushing’s syndrome.     

Evolution of critically ill patients with gastroschisis from three tertiary centers

OBJECTIVES AND INTRODUCTION:

Gastroschisis is a congenital abdominal wall defect with increasing occurrence worldwide over the past 20–30 years. Our aim was to analyze the morbidity of newborns after gastroschisis closure, with emphasis on metabolic and hydroelectrolyte disturbances in patients at three tertiary university centers.

METHODS:

From January 2003 to June 2009, the following patient data were collected retrospectively: (A) Background maternal and neonatal data: maternal age, prenatal diagnosis, type of delivery, Apgar scores, birth weight, gestational age and sex; (B) Surgical modalities: primary or staged closure; and (C) Hospital course: levels of serum sodium and levels of serum albumin in the two first postoperative days, number of ventilation days, other postoperative variables and survival. Statistical analyses were used to examine the associations between some variables.

RESULTS:

163 newborns were included in the study. Primary closure of the abdominal defect was performed in 111 cases (68.1%). The mean serum sodium level was 127.4±6.7 mEq/L, and the mean serum albumin level was 2.35±0.5 g/dL. Among the correlations between variables, it was verified that hyponatremia and hypoalbuminemia correlated with the number of days on the ventilator but not with the number of days on total parenteral nutrition (TPN); mortality rate correlated with infection. The final survival rate was 85.9%.

CONCLUSION:

In newborns with gastroschisis, more aggressive attention to hyponatremia and hypoalbuminemia would improve the outcome.     

Association of lipoprotein-associated phospholipase A₂ with characteristics of vulnerable coronary atherosclerotic plaques

Purpose

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA₂ with characteristics of vulnerable coronary atherosclerotic plaques.

Materials and Methods

We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well.

Results

Lp-PLA₂ concentration was significantly higher in both UA and SA patients [(396±36) µg/L and (321±39) µg/L, respectively] compared with the controls [(127±49) µg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91±0.15 vs. 0.85±0.11, p=0.005) and eccentricity index (EI) (0.73±0.16 vs. 0.65±0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91±0.23) mm vs. (0.63±0.21) mm, p=0.032]. Moreover, Lp-PLA₂ correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA₂ and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA₂ (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA₂ was strongly associated with both EI and fibrous cap thickness in both groups.

Conclusion

Serum level of Lp-PLA₂ is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA₂ might to be a strong risk factor and more serious for unstable angina than stable angina.     

Electrolytes assessed by point-of-care testing – Are the values comparable with results obtained from the central laboratory?

Background and Aims:

When dealing with very sick patients, the speed and accuracy of tests to detect metabolic derangements is very important. We evaluated if there was agreement between whole blood electrolytes measured by a point-of-care device and serum electrolytes measured using indirect ion-selective electrodes.

Materials and Methods:

In this prospective study, electrolytes were analyzed in 44 paired samples drawn from critically ill patients. Whole blood electrolytes were analyzed using a point-of-care blood gas analyzer and serum electrolytes were analyzed in the central laboratory on samples transported through a rapid transit pneumatic system. Agreement was summarized by the mean difference with 95% limits of agreement (LOA) and Lin’s concordance correlation (p _c).

Results:

There was a significant difference in the mean (±standard deviation) sodium value between whole blood and serum samples (135.8 ± 5.7 mmol/L vs. 139.9 ± 5.4 mmol/L, P < 0.001), with the agreement being modest (p_c = 0.71; mean difference −4.0; 95% LOA −8.78 to 0.65). Although the agreement between whole blood and serum potassium was good (p_c = 0.96), and the average difference small (−0.3; 95% LOA −0.72 to 0.13), individual differences were clinically significant, particularly at lower potassium values. For potassium values <3.0 mmol/L, the concordance was low (p_c = 0.53) and the LOA was wide (1.0 to −0.13). The concordance for potassium was good (p_c = 0.96) for values ≥3.0 (mean difference −0.2; 95% LOA −0.48 to 0.06).

Conclusions:

Clinicians should be aware of the difference between whole blood and serum electrolytes, particularly when urgent samples are tested at point of care and routine follow-up electrolytes are sent to the central laboratory. A correction factor needs to be determined at each center.     

Effects of 4 Weeks Recombinant Human Growth Hormone Administration on Insulin Resistance of Skeletal Muscle in Rats

Purpose

Effect of recombinant human growth hormone (rhGH) administration on lipid storage, and its subsequent effect on insulin sensitivity have not yet been adequately examined. Thus, we investigated the effects of rhGH treatment on muscle triglyceride (TG) and ceramide content, and insulin sensitivity after 4 weeks of rhGH administration in rats.

Materials and Methods

Fourteen rats were randomly assigned to two groups: rhGH injection group (GH, n = 7) and saline injection group (CON, n = 7). GH received rhGH by subcutaneous injections (130 µg·kg^-1·day^-1, 6 days·week^-1) for 4 weeks, while CON received saline injections that were equivalent in volume to GH group. Intramuscular TG and ceramide content and hepatic TG content were measured. To determine insulin sesitivity, oral glucose tolerance test (OGTT) and muscle incubation for glucose transport rate were performed in rats, and used as indicators of insulin sensitivity. We also examined plasm lipid profiles.

Results

After 4 weeks of rhGH treatment, the GH group had higher muscle and liver TG contents than the CON (p < 0.05). Ceramide content in GH was significantly greater than that in CON (p < 0.05). GH also had higher plasma levels of FFA (p < 0.05), glucose and insulin responses during OGTT (p < 0.05), and lower glucose transport rates in submaximal insulin concentration (p < 0.05) as compared with CON. Results indicate that rhGH treatment is associated with insulin resistance in rats.

Conclusion

rhGH treatment elevated muscle TG and ceramide content, and hepatic TG content. Thus, elevation of these compounde by rhGH treatment could contribute to the development of insulin resistance in rats.     

Elevated serum C-reactive protein as a prognostic marker in small cell lung cancer

Purpose

Elevated C-reactive protein (CRP) is associated with poor prognosis in several tumor types. The purpose of this study was to investigate serum CRP as a prognostic marker in small cell lung cancer (SCLC).

Materials and Methods

The pretreatment serum CRP level was measured in 157 newly diagnosed SCLC patients, and correlation between serum CRP level and other clinical parameters was analyzed. Multivariate analyses were performed to find prognostic markers using Cox''s proportional hazards model.

Results

The initial CRP concentration was within the normal range in 72 (45.9%) patients and elevated in 85 (54.1%) patients. There was a significant correlation between serum CRP level and the extent of disease (p<0.001), weight loss (p=0.029) and chest radiation (p=0.001). Median overall survival (OS) in the normal CRp group was significantly longer than with the high CRp group (22.5 months vs. 11.2 months, p<0.001). Extent of disease (p<0.001), age (p=0.025), and performance status (p<0.001) were additional prognostic factors on univariate analysis. On multivariate analysis, elevated serum CRp level was an independent prognostic factor for poor survival (HR=1.8; p=0.014), regardless of the extent of disease (HR=3.7; p<0.001) and performance status (HR=2.2; p<0.001).

Conclusion

High level of CRP was an independent poor prognostic serum marker in addition to previously well-known prognosticators in patients with SCLC.     

Evaluation of glutathione S-transferase P1 genetic variants affecting type-2 diabetes susceptibility and glycemic control

Introduction

Type 2 diabetes mellitus (T2DM) is associated with increased production of reactive oxygen species and a reduction in antioxidant defenses leading to oxidative stress. Glutathione S-transferases (GSTs) modulate oxidative stress. The present cross-sectional study was aimed at investigating the association between the GSTP1 gene polymorphism and T2DM and to clarify their effect on the glycemic control parameters.

Material and methods

From the Egyptian population, we enrolled 112 T2DM patients and 188 healthy controls matched for age, sex and origin. Serum lipid profile, blood-glucose level, glycated hemoglobin (HbA_1c) and body mass index (BMI) were measured. DNA was extracted from the blood samples. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile¹⁰⁵Val gene polymorphism of study participants.

Results

The frequency of the Val allele in exon 5 of the GSTP1 gene in patients with T2DM was higher than that observed in healthy controls (15.2% vs. 9.6%); the difference was considered statistically significant when compared to Ile allele carriers (p = 0.03). The presence of the GSTP1 heterozygous mutant allele Ile/Val was more common in subjects with T2DM than in the control group (30.4% and 19.2%, respectively; p = 0.02). Variation in the GSTP1 gene was associated with BMI (p = 0.02) and not associated with glycemic control parameters (fasting serum glucose and HbA_1c) or smoking-related risk of T2DM.

Conclusions

GSTP1 gene polymorphism may play a significant role in increasing the susceptibility to and risk of T2DM and obesity regardless of smoking status and had no apparent effect on HbA_1c in patients with diabetes mellitus.