Essay: The serum selenium in type 2 diabetics (T2DM) and its association with glycemic control and blood lipoproteins

ABSTRACT
Objective: To determine the serum selenium in type 2 diabetics (T2DM) and its association with glycemic control and blood lipoproteins.
Place and Duration: Diabetic clinic, Isra University hospital Hyderabad from March 2013 to February 2014.
Subject & Methods: A sample of 310 T2DM was selected according to inclusion and exclusion criteria. The blood samples were collected through a venepuncture. HbA1c was measured by Hitachi 902, Roche diagnostics analyzer and Serum selenium by atomic absorption technique. Data was analyzed on Statistix 8.1 (USA). Student`s t-test and chi-square were used for the quantitative and qualitative data respectively. Linear correlation of serum selenium with HbA1c and lipid subtractions was performed. P-value at ‘ 0.05 was defined as significant.
Results: Serum selenium deficiency (<70??g/L) was observed in 199 (64.1%) of cases. Mean ?? SD selenium in normal and deficient subjects was noted as 91.5??0.9 and 67.1??1.7 respectively (p=0.0001). An inverse association of serum selenium was observed with HbA1c, blood glucose, serum triglycerides, cholesterol, LDLc and VLDL. Conclusion: selenium deficiency in majority of type 2 diabetics. An inverse association of selenium was observed with blood glucose, HbA1c, serum triglycerides, cholesterol, LDLc and VLDL..
Key words: Selenium Diabetes mellitus Hb A1C Isra University
INTRODUCTION
The number of people with type 2 Diabetes mellitus (T2DM) is increasing due to increasing population, growing urban population, sedentary life style, and obesity.1 This epidemic of DM is particularly relevant to Pakistan.2 The WHO has estimated that in 2030, half of 333 million people living with DM will be from Asia. According to International Diabetes Federation (IDF), the number of diabetics of >20 years is going to rise from 285 million in 2010 to 439 million in 2030.3 The Pakistan occupies sixth position regarding diabetes burden in whole world.1 According to an estimate of Shera, et al4 there are 15% Pakistani’s with diagnosed DM and millions more which remain undiagnosed/unaware of having DM.4, 5 The glycosylated hemoglobin A (HbA1c) is a validated criterion of glycemic control in T2DM subjects.
The altered status of some essential trace elements and altered antioxidant minerals ratio observed in diabetic patients could have deleterious influences on the health of diabetics.6 Blood levels of trace element were not dependent on the degree of glucose control as determined by correlation analysis between HBA1c versus mineral levels.7 Serum selenium concentrations are influenced by physiological conditions such as age, diet and gender.8
The inverse relationships between Selenium status and glucose tolerance are consistent with earlier observations that suggest a link between Selenium and glucose metabolism. Observer noticed the changes in serum glucose were not accompanied by changes in insulin suggests that Selenium may affect glucose metabolism downstream of insulin, or through independent pathway of energy regulation.9
Epidemiological studies have implicated perturbations in Selenium, Copper, and Zinc metabolism in the etiology of cardio-vascular disease in diabetic subjects.10 So, the changes in trace metals appear to be associated with risk of atherosclerosis.10,11 Furthermore; low serum selenium draws much attention because of the possible role in the etiopathogenesis of cardiovascular disease.8 The objective of this study is to estimate and study the potential role of serum selenium in type 2 diabetic and its relation glycemic control.
SUBJECTS AND METHODS
A descriptive case study was conducted on diagnosed cases of T2DM attending the Diabetic OPD of Isra University hospital, and consultant private clinics, Hyderabad. A sample of 310 patients was studied over one year from March 2013 to February 2014. T2DM were selected by non-probability purposive sampling as per inclusion and exclusion criteria. The diagnosed cases of T2DM, of age 30-60 years, volunteers with normal renal function were included in the study protocol. T2DM subjects having associated systemic diseases like chronic liver disease, bone disorder, chronic kidney disease and diabetic nephropathy were excluded. This was followed by enquiry about medical history related to T2DM, duration, anti-diabetic drugs, habit of drug intake, frequency of blood glucose checking and education level were recorded on a structured proforma. Diabetes mellitus was defined as Random blood sugar (RBS) level of ‘200 mg/dl or fasting blood glucose level of ‘ 126mg/dl.12 HbA1C was used as an indicator of glycemic control. The HbA1c was performed in laboratory certified and standardized to the DCCT assay. The HbA1c was measured on automated clinical chemistry analyzer; Hitachi 902, Roche diagnostics, USA. The glycemic status was defined as controlled diabetics with HbA1c ‘7% and uncontrolled diabetics with HbA1c >7%.13 The blood samples were drawn through a venepuncture under aseptic condition using standard methods of blood sampling by trained paramedic person. Serum selenium was measured by atomic absorption method. The data was recorded on a pre-structured proforma. Informed written consent was signed on proforma. The data was analyzed on Statistix 8.1 (USA). Student`s t-test and chi-square were used for the quantitative and qualitative data respectively. Continuous variables were presented as mean??S.D and categorical data as frequencies and %. A simple linear correlation of serum selenium with HbA1c and lipid subtractions Pearson`s correlations was performed. P-value at ‘ 0.05 was defined as significant.
RESULTS
Of 310 T2DM, 112 (36.1%) were male and 112 (36.1%) were female. Mean??SD of age was noted as 47??10.7 years. Most of subjects belonged to urban population i.e. 193 (62.2%). Demography characteristics of study population are shown in table I. HbA1c <7% and ‘7% was noted in 97 (31.2%) and 213 (68.7%) of subjects respectively (p=0.001).
Mean ?? SD selenium in normal and deficient subjects was noted as 91.5??0.9 and 67.1??1.7 respectively (p=0.0001). Serum selenium ’70??g/L and <70??g/L were found in 111 (35.8%) and 199 (64.1%) of cases respectively (0.001). Serum triglycerides, total cholesterol, HDLc, LDLc and VLDL significantly differed in normal and reduced selenium cases as shown in table III. Similarly, HbA1c and blood glucose varied in diabetics with normal and reduced selenium as shown III.
Univariate and multivariate analysis revealed significant odds ratio of serum selenium with risk factors as shown in table IV. Simple linear association by Pearson`s correlation revealed significant positive association of serum selenium with HDLc; r= 0.53 and p=0.03. Serum selenium showed an inverse relationship with serum triglycerides, total cholesterol, LDLc and VLDLc as shown in table V.
Table. I. Demographic characteristics of type 2 diabetic study subjects (n=310)
Age 47??10.7 years
Male 198 (63.8%)
Female 112 (36.1%)
Rural population 117 (37.7%)
Urban population 193 (62.2%)
Obesity 87(28.0%)
Hypertension 49 (15.8%)
Dyslipidemia 174 (56.1%)
Smokers 102 (32.9%)
HbA1c (<7%) 97 (31.2%)
HbA1c (‘7%) 213 (68.7%)
Blood glucose (mg/dl) 283??60.5
Table. II. Serum selenium in type 2 diabetic subjects (n=310)
Selenium ’70??g/L Selenium <70??g/L p-value
No. of Pt. (%) 111 (35.8%) 199 (64.1%) 0.001
Mean??S.D 91.5??0.9 67.1??1.7 0.0001
Table III. Lipid profile of type 2 diabetic subjects (n=310)
Serum selenium
’70??g/L <70??g/L p-value
Triglycerides (mg/dl) 131.9??45.3 224.1??100.7 0.03
Total cholesterol (mg/dl) 155.3??25.6 211.1??43.9 0.001
HDLc (mg/dl) 38.9??8.1 33.5??9.37 0.035
LDLc (mg/dl) 97.3??17.6 119.6??31.3 0.001
VLDL (mg/dl) 42 ?? 11.5 27.3 ?? 9.7 0.001
HbA1c (%) 6??0.9 7.9??0.91 0.01
Blood glucose (mg/dl) 219.7??25.9 261.9??33.1 0.001
Table IV. Odds ratio analysis of serum selenium and risk factors
Univariate analysis Multivariate analysis
Risk factors OR* 95%CI OR* 95%CI
Dyslipidemia 2.3 1.3-4.12 1.71 1.2-2.5
Diabetes mellitus 1.3 0.6-2.11 0.67 0.4-1.01
Hypertension 1.5 0.7-2.01 0.78 1.3-3.10
*Odds ratio
Table V. Correlation of serum selenium with lipid fractions (n=310)
r-value p-value
Triglycerides (mg/dl) -0.41 0.03
Total cholesterol (mg/dl) -0.39 0.02
HDLc (mg/dl) 0.53 0.03
LDLc (mg/dl) -0.35 0.0001
VLDL (mg/dl) -0.23 0.001
HbA1c (%) -0.23 0.01
Blood glucose (mg/dl) -0.29 0.001
DISCUSSION
Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies showed positive correlation of low selenium in nutrition to enhanced risk of cardio-vascular diseases, cardiomyopathy and oncogenesis in different parts of body. 14,15
Mean ?? SD selenium in normal and deficient subjects was noted as 91.5??0.9 and 67.1??1.7 respectively (p=0.0001). Serum selenium concentrations of ’70??g/L and <70??g/L were found in 111 (35.8%) and 199 (64.1%) of cases respectively (0.001). The findings are consistent with previous studies,11 and contrary to others.18-20 The existing literature data regarding serum selenium levels in diabetic and non-diabetic subjects are controversial.21-24
In a recent study in Asia there were no important differences for serum selenium levels in T2D subjects and non-diabetic individuals.25 On the contrary; two studies showed that the mean serum selenium levels in diabetic subjects were significantly lower than in controls.26,27 In addition, a negative correlation was observed between plasma selenium and HbA1c, this confirms the findings study. 21
Other authors found a statistically significant increase in selenium levels in diabetic subjects compared to the controls. 23,28
Serum triglycerides, total cholesterol, HDLc, LDLc and VLDL significantly differed in normal and reduced selenium cases as shown in table III. Similarly, HbA1c and blood glucose varied in diabetics with normal and reduced selenium as shown III.
Univariate and multivariate analysis revealed significant odds ratio of serum selenium with risk factors as shown in table IV. Simple linear correlation revealed significant positive association of serum selenium with HDLc; r= 0.53 (p=0.03). Serum selenium showed an inverse relationship with VLDL, LDLc, total serum cholesterol and triglycerides as shown in table V. Findings are comparable to a previous study.11
A cross-sectional analysis of 8,876 adults, over a period of 20 years, participated in the Third National Health and Nutrition Examination Survey in the USA showed that high serum selenium levels were positively associated with the prevalence of diabetes.29
Serum selenium levels were associated with higher fasting plasma glucose and HbA1c similar to reported previously. 23
These inverse correlations might be explained by Selenium as a powerful anti-oxidant which plays a role in glutathione associated peroxidases in the detoxification of hydrogen peroxide and organic hydroperoxides;30 or by the role of selenoproteins present in mammalian cells and may account for the essentiality of Selenium for the anti oxidant mechanisms, normal thyroid hormone physiology, cell mediated immune responses, spermatogenesis and physiological functioning of the prostate gland.15
CONCLUSION
The study showed a selenium deficiency in majority of type 2 diabetics. An inverse association of selenium was observed with blood glucose, HbA1c, serum triglycerides, total cholesterol, VLDL and LDL. Further studies are warranted to elucidate the findings of present study.