Establishment of dry chemistry based reference intervals of renal function test parameters for the adult population of Kaski District, Nepal.

BACKGROUND: Reference intervals (RIs) for clinical chemistry test parameters are specific to the method of measurement and population under service. However, there has been no locally available dry chemistry based RIs for the Nepalese population. Thus, the present study aimed to establish dry chemistry based RIs for sodium, potassium, urea, and creatinine specific to adult populations of Kaski districts, Nepal METHODS: This was a cross-sectional study conducted at the Manipal Teaching Hospital, Pokhara, Kaski, Nepal on 360 healthy adult participants aged 18-65 years. The test parameters under study were analyzed using a fully automated OCD Vitros 350 dry chemistry analyzer following the protocols provided by the reagent kit manufacturer. The RIs were estimated using reference limits at 2.5th and 97.5th percentiles. The normal distribution of the data was tested by Kolmogorov-Smirnov, and Shapiro-Wilk tests. The differences between males and females RIs were compared by the Mann-Whitney test while age-specific RIs for each sex was compared by One-Way-ANOVA and Dunnett's Multiple Comparisons Tests. All the data were managed and analyzed using MS Excel and SPSS version 20. RESULTS: The RIs of urea, creatinine, sodium, and potassium specific to the adult population of Kaski district, Nepal are as follows: urea: 4.20-13.70 mmol/L (males: 4.70-13.99; females: 4.20-13.23); creatinine: 44.20-106.10 µmol/L (males: 48.82-106.10; females: 35.40-83.78); sodium 135-146 mmol/L (males: 135-146; females: 135-146) and potassium 3.60-5.10 mmol/L (males: 3.54-5.0; females: 3.60-5.10). These RIs were found to be different from currently used RIs provided by the reagent manufacturer. RIs of all the test parameters were significantly influenced by the age of the study participants. However, only the RIs of urea, creatinine, and potassium were significantly influenced by sex. CONCLUSIONS: The present study has for the first time established dry chemistry based RIs for selected renal function test parameters specific to the adult population of Kaski district, Nepal. This result will aid the clinician in minimizing the errors in result interpretation and making a precise clinical decision.

Association of serum magnesium level with poor glycemic control and renal functions in Nepalese patients with type 2 diabetes mellitus.

BACKGROUND: Hypomagnesaemia has been shown to be associated with type 2 diabetes mellitus (T2DM) and its complications. The present study investigated the association of hypomagnesaemia with T2DM and its complications in patients hailed mostly from the western hilly region of Nepal. METHODS: This study was conducted among 150 type 2 diabetic patients and 150 of non-diabetic controls between May to September 2016. Relevant demographic, anthropometric, physiological and biochemical variables were measured using standard protocols. Statistical analyses were performed by SPSS version 17.0. RESULTS: Hypomagnesaemia (1.7±0.2mg/dl) was present in 50% of diabetic patients and none in the healthy controls (2.0±0.2mg/dl). It was inversely correlated with levels of glycated hemoglobin (HbA1c) (r=-0.299), total cholesterol (r=-0.219), low density lipoprotein-cholesterol (r=-0.168) and creatinine (r=-0.215) and directly correlated with serum creatinine based glomerular filtration rate (eGFRcr) (r=0.196). Subjects with hypomagnesaemia were significantly older (57.4±11.5years) and had higher levels of HbA1c (8.4±1.2%) and serum total cholesterol (248.3±72.0mg/dl). The methods of diabetes control did not have a significant influence on serum magnesium level. Patient's age (OR: 1.05 (95% CI-1.01-1.09)), poor glycemic control (OR: 6.78 (95% CI-2.56-17.95)) and low eGFRcr (OR: 4.89 (95% CI-1.78-13.40)) were the significant predictors of hypomagnesaemia. CONCLUSION: Half of type 2 diabetic population under study had hypomagnesaemia without regard to the method of diabetes control. Old age, poor glycemic control, and low eGFRcr were the significant predictors of low serum magnesium in these patients. Besides their regular anti-diabetic treatment, clinicians should also consider dietary supplementation of magnesium to prevent further complications of diabetes in these patients.

Prevalence and pattern of dyslipidemia in Nepalese individuals with type 2 diabetes.

BACKGROUND: Atherogenic dyslipidemia is an important modifiable risk factor for cardiovascular disease among patients of type 2 diabetes mellitus. Timely detection and characterization of this condition help clinicians estimate future risk of cardiovascular disease and take appropriate preventive measures. The aim of this study was to determine the prevalence, pattern and predictors of dyslipidemia in a cohort of Nepalese patients with type 2 diabetes. RESULTS: We found mixed dyslipidemia as the most prevalent (88.1%) and isolated dyslipidemia (10.1%) as the least prevalent forms of dyslipidemia in our patients. The most prevalent form of single dyslipidemia was high LDL-C (73.8%) and combined dyslipidemia was high TG, high LDL-C and low HDL-C (44.7%). Prevalence of all single and mixed dyslipidemia was higher in patients with poor glycemic control and hypertension. The glycemic status of patients correlated with their fasting serum lipid profile. Dyslipidemia was associated mainly with male gender, poor glycemic control and hypertension. CONCLUSIONS: Atherogenic dyslipidemia is associated mainly with male gender, poor glycemic control and hypertension. It is highly prevalent in Nepalese patients with type 2 diabetes. Urgent lifestyle modification, sustained glycemic control and aggressive lipid lowering treatment plans are necessary to minimize the future risk of cardiovascular disease in this population.

Estimation of 10-Year Risk of Coronary Heart Disease in Nepalese Patients with Type 2 Diabetes: Framingham Versus United Kingdom Prospective Diabetes Study.

BACKGROUND: Predicting future coronary heart disease (CHD) risk with the help of a validated risk prediction function helps clinicians identify diabetic patients at high risk and provide them with appropriate preventive medicine. AIM: The aim of this study is to estimate and compare 10-year CHD risks of Nepalese diabetic patients using two most common risk prediction functions: The Framingham risk equation and United Kingdom Prospective Diabetes Study (UKPDS) risk engine that are yet to be validated for Nepalese population. PATIENTS AND METHODS: We conducted a hospital-based, cross-sectional study on 524 patients with type 2 diabetes. Baseline and biochemical variables of individual patients were recorded and CHD risks were estimated by the Framingham and UKPDS risk prediction functions. Estimated risks were categorized as low, medium, and high. The estimated CHD risks were compared using kappa statistics, Pearson's bivariate correlation, Bland-Altman plots, and multiple regression analysis. RESULTS: The mean 10-year CHD risks estimated by the Framingham and UKPDS risk functions were 17.7 ± 12.1 and 16.8 ± 15 (bias: 0.88, P > 0.05), respectively, and were always higher in males and older age groups (P < 0.001). The two risk functions showed moderate convergent validity in predicting CHD risks, but differed in stratifying them and explaining the patients' risk profile. The Framingham equation predicted higher risk for patients usually below 70 years and showed better association with their current risk profile than the UKPDS risk engine. CONCLUSIONS: Based on the predicted risk, Nepalese diabetic patients, particularly those associated with increased numbers of risk factors, bear higher risk of future CHDs. Since this study is a cross-sectional one and uses externally validated risk functions, Nepalese clinicians should use them with caution, and preferably in combination with other guidelines, while making important medical decisions in preventive therapy of CHD.

Role of leptin on the expression of low density lipoprotein receptor.

BACKGROUND & OBJECTIVES: Leptin resistance oriented hyperleptinaemia is a common problem in obese subjects in association with hypercholesterolaemia. The most common target for hypercholesterolaemia is impaired low density lipoprotein receptor (LDLR). This study was carried out to investigate whether any alteration in LDLR expression could explain the occurrence of hypercholesterolaemia in the event of hyperleptinaemia. METHODS: Expression of LDLR and SREBP2 (sterol regulatory element binding protein 2) were examined in HepG2 cells by RT-PCR and Western blotting. JAK2 inhibitor II was used to verify the effect of JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway (common mediator for cytokine signaling). Co-localization of LDLR and insulin receptor (IR) was examined by confocal microscopy. RESULTS: Leptin was found to reduce the expression of LDLR and its transcription factor SREBP2. On the other hand, a weak signal for stimulation of LDLR by leptin was noted to be mediated by JAK2 pathway. But the joint effect of the two signaling pathways kept LDLR only in depressed mode in presence of leptin. Confocal microscopy showed that LDLR made an intensively co-localized complex with insulin receptor in presence of leptin. INTERPRETATION & CONCLUSIONS: Our results show that though leptin stimulates LDLR expression very weakly through JAK-STAT signaling pathway, it mainly imposes inhibition on LDLR expression by inhibiting transcription factor SREBP2. The inter-association between LDLR and IR may be a reason to render LDLR functionally inactive in presence of leptin.

Prevalence of metabolic syndrome in Nepalese type 2 diabetic patients according to WHO, NCEP ATP III, IDF and Harmonized criteria.

BACKGROUND: Metabolic syndrome (MetS) present in type 2 diabetic patients greatly increases the risk of strokes and cardiovascular diseases. Timely detection and mapping of MetS facilitates appropriate preventive and therapeutic approaches to minimize these risks. Our study aimed to determine the prevalence of MetS among Nepalese type 2 diabetic patients using WHO (1999), NCEP ATP III (2001), IDF (2005) and Harmonized (2009) definitions and identify the diagnostic concordance and disparity resulting from these four definitions. METHODS: Clinical and biochemical data were collected for 1061 type 2 diabetic patients at Manipal Teaching Hospital, Pokhara, Nepal. The data was analyzed in order to identify prevalence of MetS in these patients. Statistical analysis included usage of Student's t- and Chi-square tests, kappa statistics and 95% confidence intervals. RESULTS: The total age adjusted prevalence rates of MetS were 80.3%, 73.9%, 69.9% and 66.8% according to Harmonized, NCEP ATP III, WHO and IDF definitions, respectively. Prevalence increased with the age and was higher in females (p <0.001) according to WHO, NCEP ATP III and Harmonized definitions. Patients of Dalit community had the highest prevalence (p<0.05) according to NCEP ATP III and Harmonized definitions while Mongoloid and Newar patients had the highest prevalence (p <0.05) according to WHO and IDF definitions, respectively. Prevalence was also highest among patient engaged in agriculture occupation. Central obesity and hypertension were respectively the most and the least prevalent components of MetS. The highest overall agreement was between Harmonized and NCEP ATP III definitions (κ =0.62, substantial) and the lowest between WHO & IDF definitions (κ=0.26, slight). The Harmonized definition had the highest sensitivity (99.9%) and negative predictive value (98.9%) while NCEP ATP III definition had the highest specificity (98.9%) and positive predictive values (99.9%) in identifying the cases of MetS. CONCLUSIONS: The prevalence of MetS among Nepalese type 2 diabetic patients was very high suggesting that these patients were at increased risk of strokes, cardiovascular diseases and premature death. The Harmonized definition was the most sensitive while NCEP ATP III and IDF definitions were the most specific in detecting the presence of MetS in Nepalese type 2 diabetic patients.

A prevalence of thyroid disorder in Western part of Nepal.

BACKGROUND: Nepal is an endemic area with regards to iodine deficiency, as well as a nutritional iodine deficiency is thought to be prevalent in all the Himalayan, sub-Himalayan and the Terai regions of Nepal. Thyroid dysfunction is a major public health problem among the Nepalese population. OBJECTIVES: The objective of this study was to find out the prevalence of thyroid dysfunction among the patients who attended the Charak Hospital, Pokhara, Nepal. MATERIALS AND METHODS: A hospital based study was undertaken by using the data which was retrieved from the thyroid function tests, which included free T3, free T4 and TSH, from the register which was maintained in the Department of Biochemistry of the Charak Hospital, Pokhara, Nepal, from 1(st) January, 2011 to 30th December, 2012. Descriptive statistics and testing of the hypothesis were used for the analysis by using the EPI INFO and the SPSS version 16 softwares. RESULTS: The total number of cases was 1504, which included 23.20% males and 76.80% females. The prevalence of thyroid dysfunction was 17.42%. Females had more thyroid dysfunction than the males. Hypothyroidism (2.26%) and subclinical hypothyroidism (10.50%) had higher prevalences as compared to hyperthyroidism (1.59%) and subclinical hyperthyroidism (3.05%) in the western region of Nepal. A higher prevalence of the thyroid dysfunction was observed in the subjects who ages were above 41-50 years. CONCLUSION: Females and people of advanced ages were more vulnerable to thyroid dysfunction in the population. Hypothyroidism and subclinical hypothyroidism were preponderant, followed by subclinical hyperthyroidism.

Assessment of biochemical profiles in premenopausal and postmenopausal women with breast cancer.

OBJECTIVE: The study was conducted to assess biochemical profiles in premenopausal and postmenopausal women having breast cancer. MATERIALS AND METHODS: A hospital based case control study was carried out at Manipal Teaching Hospital (MTH), Pokhara, Nepal. The analysed variables were age, metabolic profile including total cholesterol, triglycerides, HDL-C, LDL-C, blood sugar, insulin concentration, C-peptide, HbA1c and selenium. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. RESULTS: In premenopausal women, significant differences were noted for total cholesterol (P value <0.001), triglycerides (P value 0.002), HbA1c level (P value <0.001), insulin concentration (P value 0.030), C-peptide concentration (P value 0.001), and selenium (P value <0.001) between cases and controls. Insignificant results were found for HDL-C (P value 0.749), LDL-C (P value 0.933), blood sugar (P value 0.59) and BMI (P value 0.746). Similarly, significant difference in total cholesterol (P value <0.001), triglycerides (P value 0.001), LDL-C (P value <0.001), HDL-C (P value 0.025), blood sugar (P value <0.001), insulin concentration (P value <0.001), c-peptide concentration (P value <0.001), HbA1c level (P value <0.001) and selenium (P value <0.001) were observed for postmenopausal patients and controls. CONCLUSIONS: Assessing metabolic changes and their management may be important for control of breast cancer and increased survival.

Liver involvement in multiple myeloma: a hospital based retrospective study.

OBJECTIVE: This study was to assess liver involvement in multiple myeloma with the aid of liver function tests. MATERIALS AND METHODS: A hospital based retrospective study was undertaken using data retrieved of multiple myeloma from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2007 and 28th February, 2012. We collected biomarkers of liver profiles including bilirubin (Total, Direct and Indirect), total protein, albumin, AG ratio, SGOT, SGPT, ALP, γGT, LDH, ferritin, renal profile and hematological profile. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. RESULTS: Out of 37 cases of multiple myeloma, serum level of AST, ALT, ALP, γGT and LDH were increased above the cut-off point in 22 (59.5%), 24 (64.86%), 13 (35.13%), 9 (24.3%) and 11 (29.7%) respectively. The mean values of AST (65.5±28.18 U/L), ALT (68.37±29.74 U/L), ALP (328.0±148.4 U/L), γGT (44.5±29.6 U/L) and LDH (361.7±116.5 U/L), total protein (9.79±1.03 gm/ dl) were significantly increased when compared with controls. In contrast, albumin (3.68±0.43 gm/dl) and the AG ratio (0.62±0.15) were significantly decreased. Similarly, anemia, hyperuricemia, azotemia, hypercalcaemia and Bence Jones proteinuria were found in 30 (78.9%), 27 (71.1%), 19 (51.5%), 15 (39.5%) and 16 (42.1%) respectively, in cases of multiple myeloma. CONCLUSIONS: While clinical manifestation of liver disease among the multiple myeloma was not common, abnormalities in liver function were characteristic.