Home About Us Contact Us

Official Journals By StatPerson Publication

Table of Content - Volume 11 Issue 3 - September 2019


 

Comparative assessment of renal function between type II diabetes mellitus and non-diabetic individuals

 

Hasit D Lad1, Dilipkumar M Kava2*

 

1Associate Professor, 2Tutor, Department of Biochemistry, SMIMER, Surat, Gujrat, INDIA.

 Email: hasitlad@gmail.com

 

Abstract               Background: Renal function test commonly used in clinical laboratory to diagnose various renal disorder like glomerulonephritis, and to monitor the progression of renal disease. In present study we have make an effort to carry out various renal function test in diabetes and non-diabetic individuals and compared result of renal function tests with each other. We have also try to find cause or reason for to established relationship between renal function and diabetes. Material and methods: Present study carried out in tertiary care hospital Surat. We have analyzed liver function tests like serum urea, creatinine, uric acid, calcium and phosphorous in diabetic and non-diabetic individuals. These parameters are measured in Erba XL-640 fully auto chemistry analyzer. We have also measured height and weight based on this BMI calculated. Statistical data analysis done by SPSS v16 software. Result and discussion: In present study we have observed significant (p<0.001 for all) higher level of serumurea, creatinine, uric acid, calcium and phosphorousin diabetic subjects compared to non-diabetic individuals. Serum level of urea, creatinine, uric acid, calcium and phosphorous found higher in all subjects categorized by age wise like 35-44 years, 45-54 years, 55-64 years and more or 65 years compared to non-diabetic individuals. Serum level of urea, creatinine, uric acid, and calcium and phosphorousin all BMI groups are higher in diabetic compared to non-diabetic individuals. Conclusions: Individuals with type II diabetes have a higher incidence of renal function test abnormalities than non-diabetic individuals. The most common abnormality is increased in urea, creatinine and uric acid. Any diabetic patient found to have a slightly higher level of urea, or uric acid compared to other should have to screen for treatable causes of chronic kidney disease, which are found with increased incidence in type II diabetes.

Key Word: RFT, GFR, BMI and type II Diabetes mellitus.

 

 

INTRODUCTION

Diabetes mellitus is characterized by chronic hyperglycemia, that is, high blood glucose due toderangement in carbohydrate, fat, and protein metabolism. Diabetes mellitus is associated with absolute orrelative deficiencies in insulin secretion, insulin action or both1,2. Diabetes mellitus is classified primarily into Type I and Type II. Type I Diabetes mellitus is mainly idiopathicor caused by autoimmune disorders. Type II Diabetes mellitus arises from insufficient production of the hormone insulin from beta cells of the pancreas or in conditions where the peripheral receptors; primarily muscles, liver and fat tissue do not respond adequately to normal insulin levels known as insulin resistance3. Diabetic nephropathy occur in approximately in one third of type II diabeticpatients4 .In diabetic Nephropathy a number of serum level of renal marker increased which associated with significant morbidity and mortality5. It leads to eventually chronic kidney disease, sometimes required dialysis and kidney transplantation6. A number of life style factor are known to be important to the development of Type II Diabetes, including obesity(BMI > 30), lack of physical activity, poor diet, stress and urbanization7. Higher level of uric acid mainly seen in gout, is strongly associated with insulin resistance syndrome, an established risk factor for type II diabetes.8,9 This link may be translated into an independent association between hyperuricemia and the future risk of type II diabetes. Indeed, studies of individuals with impaired glucose levels have suggested that hyperuricemia is an independent risk factor for diabetes10,11. Furthermore, the Rotterdam study of individuals 55 years and older reported similar results12. In present study we have make an effort to compare result of renal marker like serum urea, creatinine, uric acid, calcium and phosphorous level in diabetic and non-diabetic subjects with various age groups and various BMI groups.

 

MATERIAL AND METHODS

Study was conducted at tertiary care hospital in Surat, Gujarat, after obtaining necessary ethical clearance from the institutional ethical committee. A total number of 149 diabetics and 149 controls between the age group of 35-65 or above years were included in this study. We have analyzed liver function tests like serum urea, creatinine, electrolytes, uric acid, calcium and phosphorous and also measured FBS, PPBS by Erba XL-640 fully auto biochemistry analyzer. We have also measured HbA1c by HPLC based Bio Rad D10 analyzer. We have also measure anthropological data like height, weight and based on that BMI was calculated in kg/m2. Statistical analysis done by using SPSS V16 software. Student’s’ test was used for present study and p value <0.05 was considered statistically significant and p value <0.01 and p<0.001 was considered to be highly statistically significant.                We have divided diabetic and non-diabetic subjects based on age group like 35-44 years, 45-54 years, 55-64 years and ≥65 years and also divided based on BMI wise like <23 kg/m2, 23-25 kg/m2, 25-29.9 kg/m2 and ≥30 kg/m2.


 

RESULT

Table 1: Comparison of serum level of urea, creatinine, uric acid, and calcium and phosphorous in diabetic and non-diabetic subjects

Sr. no

Parameter

Control (149)

Diabetic subjects (149)

p value

1

FBS

93 ± 11

199 ± 91

<0.001

2

PPBS

104 ± 14.8

262 ± 138

<0.001

3

HbA1c

6 ± 0.53

9.58 ± 2.9

<0.001

4

Urea

21.97 ± 6.8

24.18 ± 8.87

<0.01

5

Creatinine

1.14 ± 1

1.17 ± 0.25

<0.001

6

Uric acid

5.41 ± 1.71

5.81 ± 1.16

<0.001

7

Calcium

9.28 ± 1.13

9.89 ± 0.82

<0.001

8

Phosphorous

3.61 ± 0.74

3.7 ± 0.6

<0.05

As per above mention table we have observed significant (p<0.001) higher level of FBS, PPBS and HbA1c in diabetic compared to non-diabetic subjects. Serum level of urea (p<0.01), creatinine, uric acid, calcium (p<0.001) and phosphorous (p<0.05) are significantly higher in diabetic subjects compared to non-diabetic individuals.

 

Table 2: Comparison of serum level of urea, creatinine, uric acid, calcium and phosphorous in diabetic and non-diabetic individuals in age group of 35-44 years, 45-54 years, 55-64 years and more or 65 years.

 

35-44 year

45-54 year

55-64 year

≥65 year

 

Diabetic subjects

(n=38)

Control subjects

(n=75)

Diabetic subjects

(n=44)

Control subjects

(n=30)

Diabetic subjects

(n=46)

Control subjects

(n=19)

Diabetic subjects

(n=18)

Control subjects

(n=10)

Urea (mg/dl)

22.26 ± 10.06

21.88 ± 6.1

25.48 ± 8.8

21.23 ± 9.23

24.22 ± 6.37

21.42 ± 5.86

25.94 ± 11.44

24.9 ± 8.10

p Value

0.8

<0.05

0.1

0.8

Creatinine

(mg/dl)

1.22 ± 0.2

1.0 ± 1.39

1.18 ± 0.22

1.04 ± 0.22

1.18 ± 0.26

1.13 ± 0.19

1.24 ± 0.26

1.08 ± 0.27

p Value

<0.05

<0.01

0.45

0.11

Calcium

(mg/dl)

9.8 ± 0.8

9.34 ± 1.3

9.8 ± 0.7

9.38 ± 0.97

10 ± 1

9.41 ± 0.76

9.9 ± 0.9

9.28 ± 0.99

p Value

<0.05

<0.05

<0.05

0.1

Phosphorous (mg/dl)

3.81 ± 0.6

3.6 ± 0.83

3.69 ± 0.67

3.49 ± 0.62

3.69 ± 0.64

3.51 ± 0.45

4.09 ± 0.47

3.62 ± 0.57

p Value

0.16

0.51

0.26

<0.05

Uric acid

(mg/dl)

5.87 ± 1.1

5.46 ± 1.86

5.68 ± 1.11

5.14 ± 1.0

5.92 ± 1.41

5.36 ± 1.1

5.86 ± 0.77

5.17 ± 3.45

p Value

0.21

<0.05

0.12

0.51

Above mention table shows that, serum level of urea and uric acid significantly (p<0.05) higher in age group of 45-54 years in diabetic compared to non-diabetic individuals, and also similar pattern observed in all age groups but non-significant. Significantly higher(p<0.01) level of creatinine found in age group of 35-44 and 45-54 years in diabetic compared to non-diabetic individuals, in other groups also same finding was observed but not significant. Serum level of calcium found significantly (p<0.05) high in all age group except in more or 65 years in diabetic compared to non-diabetic subjects. Serum level of phosphorous found significantly (p<0.05) high in age group of more or 65 years in diabetic compared to non-diabetic subjects.

Table 3: Comparison of serum level of urea, creatinine, uric acid, calcium and phosphorous between diabetic and non-diabetic individuals in BMI group of <23 kg/m², 23-24.9 kg/m², 25-29.9 kg/m² and ≥30 kg/m².

BMI (kg/m²)

< 23

23-24.99

25 – 29.99

≥30

 

Diabetic subjects

(n=4)

Control subjects

(n=17)

Diabetic subjects

(n=27)

Control subjects

(n=54)

Diabetic subjects

(n=99)

Control subjects

(n=73)

Diabetic subjects

(n=19)

Control subjects

(n=5)

Urea (mg/dl)

24.75 ± 7.4

22.9 ± 8.4

24.1 ± 7.3

20.7 ± 4.8

24 ± 9.6

22 ± 7.5

21.7 ± 6.5

21 ± 5.8

p Value

0.6

<0.05

0.14

0.82

Creatinine

(mg/dl)

1.75 ± 0.22

0.98 ± 0.15

1.45 ± 0.22

1.28 ± 1.6

1.13 ± 0.23

1 ± 0.2

1.18 ± 0.3

1 ± 0.08

p Value

<0.001

0.8

<0.01

0.2

Calcium

(mg/dl)

10 ± 0.5

9.4 ± 1.15

9.8 ± 0.8

9.2 ± 1.7

9.9 ± 0.9

9.26 ± 1

9.8 ± 0.7

10 ± 0.4

p Value

0.32

0.08

<0.001

0.55

Phosphorous (mg/dl)

4.3 ± 0.78

3.5 ± 0.7

3.84 ± 0.67

3.6 ± 0.86

3.8 ± 0.6

3.6 ± 0.6

3.87 ± 0.4

3.68 ± 1.2

p Value

<0.05

0.7

<0.05

0.4

Uric acid

(mg/dl)

6.85 ± 0.49

5 ± 0.94

5.9 ± 1.5

5.5 ± 1.6

5.7 ± 1

5.4 ± 1.9

5.77 ± 1

5.6 ± 0.7

p Value

<0.01

0.28

0.18

0.72

 


Above table shows that, serum level of urea was significantly higher in 23-24.99 kg/m2 BMI group in diabetic compared to non-diabetic subjects, same pattern was observed in all BMI groups but not significant. Serum level of creatinine was found significant high in <23 and 25-29.9 kg/m2 BMI groups in diabetic subjects compared to non-diabetic subjects, same pattern was found in all other BMI groups but not significant. Serum level of calcium was significant high in 25-29.9 kg/m2 BMI groups in diabetic compared to non-diabetic subjects, same pattern was observed in all other BMI groups but non-significant. In case of phosphorous significant high level was found in <23 and 25-29.9 kg/m2 BMI groups in diabetic subjects compared to non-diabetic subjects, same pattern observed in all BMI groups but not significant. Significant high level of uric acid found in <23 kg/m2 BMI groups in diabetic subjects compared to non-diabetic subjects.

 

DISCUSSION

We have carried out this study in 149 diabetic and 149 non-diabetic subjects, they are further divided in various age groups, in diabetic subjects there are 38, 44, 46 and 18 subjects in age groups of 35-44 years, 45-54years, 55-64 years and 65 or more years respectively. And there are 75, 30, 19 and 10 control subjects in respective age groups. We have also divided subjects in BMI group of <23kg/m2, 23-24.9 kg/m2, 25-29.9 kg/m2 and ≥ 30 kg/m2, from there are 4, 27, 99 and 19 are diabetic subjects respectively out of total 149 subjects, and 17, 54, 73 and 5 are control subjects respectively out of total 149 subjects. In our study we have observed significant (p<0.01) higher level of serum urea (24.18 ± 8.87mg/dl) in diabetic subjects compared to non-diabetic (21.97 ± 6.8mg/dl) subjects. In our study we have observed significant (p<0.01) higher level of serum creatinine (1.17 ± 0.25mg/dl) in diabetic subjects compared to non-diabetic (1.14 ± 1.0 mg/dl) subjects (table-1).Impairment in renal function is assessed by estimating the serum urea levels and the serum creatinine levels.In study conducted by P Gulabkunvar etal.13 Observed that 58.3% of diabetes mellitus type II showed significant (p<0.05) higher serum urea levels and significant higher creatinine levels. A research conducted by Anjaneyulu et al 2004 had found that increase urea and serum creatinine in diabetic rats indicate progressive renal damage14, our study have similar finding too. SugamShrestha et al also found strong correlation between fasting blood sugar and serum urea level15, which in similar pattern as finding of our study. Manjunathaet al concluded in their study that blood urea andcreatinine is accepted to assess the renal function16. As diabetes mellitus is the major cause of renal morbidity and mortality, so a good control over the sugar level can halt the progression of renaldamage, which is also in similar pattern with finding of our study.                 Serum level of urea and uric acid significantly (p<0.05) higher in age group of 45-54 years in diabetic compared to non-diabetic individuals, and also similar pattern observed in all age groups but non-significant. Significantly higher (p<0.01) level of creatinine found in age group of 35-44 and 45-54 years in diabetic compared to non-diabetic individuals, in other groups also same finding was observed but not significant. Serum level of calcium found significantly (p<0.05) high in all age group except in more or 65 years in diabetic compared to non-diabetic subjects. Serum level of phosphorous found significantly (p<0.05) high in age group of more or 65 years in diabetic compared to non-diabetic subjects (table 3). All these finding of renal biochemical parameters are similar with finding of study conducted by Manjunatha etal16. Serum level of urea was significantly higher in 23-24.99 kg/m2 BMI group in diabetic compared to non-diabetic subjects, same pattern was observed in all BMI groups but not significant. Serum level of creatinine was found significant high in <23 and 25-29.9 kg/m2 BMI groups in diabetic subjects compared to non-diabetic subjects, same pattern was found in all other BMI groups but not significant. Serum level of calcium was significant high in 25-29.9 kg/m2 BMI groups in diabetic compared to non-diabetic subjects, same pattern was observed in all other BMI groups but non-significant. In case of phosphorous significant high level was found in <23 and 25-29.9 kg/m2 BMI groups in diabetic subjects compared to non-diabetic subjects, same pattern observed in all BMI groups but not significant. Significant high level of uric acid found in <23 kg/m2 BMI groups in diabetic subjects compared to non-diabetic subjects (table 3), all these finding of renal function parameters are correlate with study conducted by Sugam et al15. Significant higher level of uric acid observed in type II diabetic subjects compared to non-diabetic subjects which is in correlation with study conducted by other author8,9. This link may be translated into an independent association between hyperuricemia and the future risk of type II diabetes. Indeed, studies of individuals with impaired glucose levels have suggested that hyperuricemia is an independent risk factor for diabetes10,11Finding of this study also correlate with findings of our study. Furthermore, the Rotterdam study of individuals 55 years and older reported similar finding which are correlate with our findings12.

The biological mechanisms underlying the association between serum uric acid and development of diabetes remain a matter of debate. Hyperuricemia may lead to endothelial dysfunction and nitric oxide inhibition, which in turn contribute to insulin resistance and thus, diabetes17. This is supported by findings that fructose-induced hyperuricemia in rats leads to insulin resistance along with other components of metabolic syndrome, and these conditions are improved by decreasing uric acid levels17,18. However, it is also conceivable that elevated serum uric acid levels may reflect prediabetes status, particularly at the renal level, although our observed association was independent of fasting glucose, triglycerides, and serum creatinine. Higher insulin levels associated with prediabetes can reduce renal excretion of uric acid 19-21 as insulin can stimulate the urate-anion exchanger22 or the Na-dependent anion co-transporter in brush border membranes of the renal proximal tubule23 and increase renal urate reabsorption. Thus, although our study provides support for the independent association between serum uric acid levels and the risk of incident type II diabetes, any causal inference remains to be clarified by future studies.

 

CONCLUSION

Renal function is assess by estimating parameters like urea, creatinine, uric acid, calcium and phosphorous in type II diabetes mellitus. We have found significant higher level of urea and creatinine in diabetic subjects compared to non-diabetic subjects. Based on our and other researchers findings increased in level of urea and creatinine lead to renal damage in diabetes mellitus. We have also observed significant higher level of uric acid in diabetic subjects compared to non-diabetic subjects which indicate prospective significance of uric acid level with diabetes. With increasing level of uric acid may lead to or associated with development of diabetes mellitus. Significant higher level of calcium and phosphorous in diabetic and non-diabetic subjects, which indicate correlation between calcium and phosphorous level with development of diabetes. Increased level of urea, creatinine, and uric acid in all age groups in diabetes compared to non-diabetes, which indicate significant correlation between these parameters rise and development of future diabetes. Increased level of urea, creatinine, and uric acid in all BMI groups in diabetes compared to non-diabetes, which indicate significant correlation between these parameters rise and development of future diabetes with obese patients.

 

REFERENCES

  1. Alberti, K.G and P.Z Zimmet, (1998): Definition, diagnosis and classification of diabetes mellitus and its complications Part 1,Diagnosis and classification of Diabetes Mellitus, Diabetic Medicine, 15,539-553
  2. Idonije, B.O., Festus O. and Moluba O. (2011) Research Journal of Medical Sciences, 5(1), 1-3
  3. Shoback, David G. G and Dolores (2011). Greenspan's basic and clinical endocrinology,9(1),17
  4. Rehman G, Khan SA and HamayunM.Studies on diabetic nephropathy and secondary disease in type 2 diabetics. Int. J. Dia. Dev.Ctries, 25:25-29, (2005)
  5. Puepet FH, Agaba E and Chuhwak C. Some metabolic abnormalites in type 2 diabetes injos North Central Nigeria, Nig . J Med ,12 : 193 – 197 (2003 )
  6.  DiabetesProgramme ― World Health Organization .Retrieved 22 April 2014.
  7.  WILLIAMS text book of Endocrinology (12th edition). Philadelphia: Ellevier / saunder. pp .1371 – 1435 .ISBN 978 -1 – 4377– 0324 – 5.
  8. Cook DG, Shaper AG, Thelle DS, et al. Serum uric acid, serum glucose and diabetes: relationships in a population study. Postgrad Med J. 1986;62(733):1001-1006.
  9. Herman JB, Goldbourt U. Uric acid and diabetes: observations in a population study. Lancet. 1982;2(8292):240-243.
  10. Niskanen L, Laaksonen DE, Lindstrom J, et al. Serum uric acid as a harbinger of metabolic outcome in subjects with impaired glucose tolerance: the Finnish Diabetes Prevention Study. Diabetes Care. 2006;29:709-711.
  11. Kramer CK, von Muhlen D, Jassal SK, et al. Serum uric acid levels improve prediction of incident type 2 diabetes in individuals with impaired fasting glucose: the Rancho Bernardo Study. Diabetes Care. 2009;32:1272-1273.
  12.  Dehghan A, van Hoek M, Sijbrands EJ, et al. High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care. 2008;31:361-362.
  13. Vidula B, Jee W J. Choi,a Sung Woo Kim et al: Serum uric acid level and risk of type II diabetes. Prospective study.J amjmed.2010.03.027
  14. Anjaneyulu, M; Chopra, K, an anti-oxidant bioflavonoids, attenuates diabetic nephropathy in rats. Clinical and Experimental Pharmacology and Physiology 2004; 31: 244-8.
  15. Sugam S, Prajwal G, Rojeet S et al: 1National college for Advanced Learning, Lainchour, Kathmandu 2Department of Biochemistry, Institute of Medicine, TU Teaching Hospital, Kathmandu.
  16. Deepa.K, Manjunathagoud B.K, OinamSarsina Devi, et al: 1Department of Biochemistry, JSS Medical College, Mysore, India. 2Department of Biochemistry, SIMS and RC, Mukka, Mangalore, India 3Department of Nursing, Vidya Nursing College, Kapu, Udupi, India. 4Department of Pathology, KMC, Manipal University, Manipal, India
  17. Nakagawa T, Tuttle KR, Short RA, et al. Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol. 2005;1:80-86.
  18. Hallfrisch J. Metabolic effects of dietary fructose. FASEB J. 1990;4: 2652-2660.
  19. Ter Maaten JC, Voorburg A, Heine RJ, et al. Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects. Clin Sci. 1997;92:51-58.
  20. Facchini F, Chen YD, Hollenbeck CB, et al. Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA. 1991;266:3008-3011.
  21. Muscelli E, Natali A, Bianchi S, et al. Effect of insulin on renal sodium and uric acid handling in essential hypertension. Am J Hypertens. 1996;9:746-752.
  22. Enomoto A, Kimura H, Chairoungdua A, et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002;417(6887):447-452.
  23. Choi HK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med. 2005;143:499-516.