Serum Levels of Creatinine in Newly Diagnosed Type 2 Diabetics with hypertension of Karnataka State, South India

Article Information

Sujatha Narayana Rao1*, Kuldeep GB2, Mukesh Sharma3
1Professor, Department of Biochemistry, AECS Maruthi Dental College, Bangalore
2Chief Medical Administrator, Department of Medicine, Shri Krishna Sevashrama Hospital, Bangalore
3Scientist, SMS Medical College, Jaipur

*Correspondence to: Sujatha Narayana Rao, Department of Biochemistry, AECS Maruthi Dental College, Bangalore, India. E-mail: sujatharao.8@gmail.com

Received: April 12, 2020; Accepted: April 30, 2020; Published: May 05, 2020

Copyright: ©2020 Rao SN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation: Rao SN, Kuldeep GB, Sharma M. Serum Levels of Creatinine in Newly Diagnosed Type 2 Diabetics with hypertension of Karnataka State, South India. J Clin Endocrinol Diabetes Res. 2020; 1(1):003.

View / Download Pdf
Abstract

Background: Type 2 Diabetes Mellitus is the biggest silent lifestyle epidemic in the human history. Kidney disease is one of its long-term complications.It warrants an immediate attention for research.

Aim: This study aims to evaluate the levels of serum creatinine in healthy, newly diagnosed (N.D.) Type 2 Diabetics, N.D. type 2 Diabetics with hypertension and in Diabetics with Nephropathy to explore the pattern of Serum Creatinine levels.

Method: In a study involving a total of 297 Individuals of Bangalore, Karnataka State, South India, Glycated hemoglobin (HbA1c) and serum creatinine were estimated in the above 4 groups. Results were analyzed by Statistical Analysis version 24- ANOVA & Tukey’s post hoc test.

Result: Significantly higher serum Creatinine levels in N.D. type 2 Diabetics with hypertension group than healthy group and significantly higher creatinine levels in Diabetic Nephropathy group than N.D. Type 2 Diabetics with Hypertension group were noted.

Conclusion: Serum creatinine levels were gradually increasing from Healthy to N.D. Type 2 Diabetics and then to N.D. Type 2 Diabetics with hypertension and the highest level was noted in diabetics with nephropathy. So, regular monitoring of creatinine levels among hypertensive diabetics is needed to prevent further complications like diabetic nephropathy in them.

Keywords

Glycated Hemoglobin; HbA1c; Hypertension; Newly Diagnosed (N.D) type 2 Diabetics; Serum Creatinine

Article Details

Introduction

Type 2 Diabetes Mellitus (DM) characterized by hyperglycemia due to inefficient insulin, is the biggest silent epidemic in the human history, has its long-term complications as kidney disease, retinopathy, neuropathy and cardiovascular accidents. DM is affecting millions of people worldwide each year [1-3] and is extremely common in India, affecting almost 70 million individuals by 2025 [4,5]. This makes India ‘The Diabetic capital of the world’ [6,7]. Glycated Hemoglobin (HbA1c) is used to determine hyperglycemia. HbA1c reflects the blood glucose level over the previous 3 months [8,9].

Creatinine is an end product formed from creatine phosphate, this conversion is spontaneous and non-enzymatic. Amount of creatinine formed is not affected by diet, age or exercise and is dependent on the total muscle mass of the body. Since its production is continuous, its blood level will not fluctuate much making creatinine an ideal substance for clearance test to assess Glomerular Filtration Rate (GFR) as part of Kidney Function Test. So, its level in serum is indicative of renal function [10].

As serum creatinine levels were reported as biological markers for kidney function, several investigators have reported increased serum creatinine in Type 2 Diabetes. Shrestha S et al., [11] in Nepal in 2008, Ediale Joshwa [12] et al., in 2017 in Nigeria , Kanwar G et al [13] in North India in 2015, SA Bamaniker et al., [14] in West India in 2016 through their studies among Type 2 Diabetic population, have observed increased levels of serum creatinine .

Increased serum creatinine levels were also noted in hypertension by Joseph Coresh et al., [15] in 2001 in their study among Hypertensive in United States and, also by Schmeider RE et al., [16] in 1995 in their 6 year follow up study.

Pandya D et al., [17] in 2016 through their study in North India, among 3 different groups- Type 2 Diabetics, Hypertensives, CKD patients, also have reported elevated creatinine in all these 3 different groups. Patel V et al., [18] in 2018 reported the association between diabetes, kidney diseases, obesity and hypertension through their research findings.

However, Joran H et al., [19] in 2010 had reported low creatinine levels through their study of Type 2 Diabetics among Caucasians.

The fact that serum creatinine levels in N.D. Type 2 Diabetics individuals with and without hypertension have not been studied till date, inspired us to conduct this study along with the study of diabetic nephropathy patients and healthy individuals for better comparison.

Moreover, our study is important because of the enormous number of people afflicted with Diabetes and those likely to become diabetic every year. Early detection and timely action reduce the economic burden associated with diabetes [7].

Our study aims to evaluate the pattern of serum creatinine levels among Newly Diagnosed (N.D) Type 2 Diabetics with and without hypertension and also, in cases of diabetic nephropathy of Bangalore, Karnataka State, South India.

Materials & Methods

This was a cross sectional study conducted at the Shree Krishna Sevashrama Hospital, Bangalore, Karnataka, South India between December 2017 to August 2019. A total of 297 adult individuals were included in this study, matched for age and gender. After obtaining the Institutional Ethical Committee approval, informed consent was taken from all the individuals participated in the study.

Age and gender of the individuals were obtained from their hospital records. The individuals were categorized into 4 groups, based on their HbA1c levels as per W.H.O. criteria.

Inclusion Criteria:

Group I included Healthy controls with HbA1c equal to or below 5.6.
Group II included N.D. type 2 Diabetics with HbA1c level 6.5 or above.
Group III included N.D. type 2 Diabetics with hypertension with HbA1c level 6.5 or above.
Group IV included Diabetic Nephropathy with HbA1c above 6.5

Exclusion criteria for all the above 4 groups included pregnant and lactating women. Individuals taking medications were excluded from the first three group’s figure 1

Figure 1: Flow chart for the selection of the study population

Collection of Sample

After an overnight fast, blood sample were obtained for Biochemical test. Sample collection involved venous whole blood sample. Portion of it was transferred to EDTA tubes for the analysis of HbA1c and the other portion was allowed to clot. Serum was separated and used for the analysis of serum creatinine.

Analysis

Analysis was done using Olympus AV Auto analyzer, using DiaSys reagents manufactured by DiaSys Diagnostic system, GmbH, Holzheim, Germany.

HbA1c was measured using particle enhanced Immunoturbidimetric method [20] and the desirable Range was ≤ 5.6 for healthy. 5.7 – 6.4 for prediabetes, ≥ 6.5 for Diabetes. Creatinine was analyzed by Jaffe s method [21] and the desirable Range for creatinine was 0.6 – 1.4 mg/dl. Result of all the above parameters were expressed as mean with standard deviation.

Statistical Analysis

Data were analyzed using SPSS statistical version 24. One-way Analysis of Variance (ANOVA) was performed to compare the means of the four populations followed by Tukey’s multiple comparison post hoc test. The statistical difference between the groups was measured by ANOVA and among the groups, which group specifically differed significantly was measured by Tukey’s post hoc test. In this study, ANOVA with Tukey’s post hoc test was chosen because of unequal sample size between the groups. Results of all the tests with p<0.05 were considered statistically significant, with p<0.01 were considered highly significant.

Results

Table 1 displays the level of HbA1c, serum Creatinine in four different populations. Among these, only in N.D. Diabetics with hypertension group (1.517 ± 0.190) and in Diabetic Nephropathy group (6.205 ± 0.3178) Serum Creatinine levels were higher than the normal Range. 

Type of Groups

N

HbA1c

Serum Creatinine

mg/dl

Healthy

68

4.83±0.47

0.897±0.128

N.D.Type2 Diabetics

124

8.31±1.52

0.988±0.130

N.D.Type2 Diabetics with Hypertension

53

9.64±1.80

1.517±0.190

Diabetics with Nephropathy

52

10.32±0.10

6.205±3.178

 Table 1. Descriptive statistics for HbA1c, Serum Creatinine levels in Healthy, N.D. Type 2 Diabetics, N.D. Type 2 Diabetics with Hypertension, Type 2 Diabetics with Nephropathy Groups.

In Healthy group (0.897 ± 0.128) and in N.D. Type 2 Diabetics group, (0.988 ± 0.130) Serum Creatinine levels were within the normal range.

Table 2 displays the results of ANOVA, performed between all the four groups. It was found that significant difference existed between the groups (F=63.616, P<0.01). 

Serum Creatinine Levels 

Sum of Squares

df

Mean Square

F

Sig.

Between Groups

7.212

4

1.803

63.616

 

 

0.000

 

 

Within Groups

6.576

232

0.028

Total

13.788

236

 

 Table 2. ANOVA Report: Significant difference in Serum Creatinine levels between Healthy, N.D. Type 2 Diabetics, N.D. Type 2 Diabetics with Hypertension, Diabetics with Nephropathy Groups.
Significant at p<0.05. Highly Significant at p<0.01.

Table 3 reveals the results of the Tukey’s post hoc test. Significant difference is noted (P=0.000) in the serum creatinine levels between Newly Diagnosed type 2 Diabetics and Newly Diagnosed type 2 Diabetics with hypertension. Significant difference is noted (P=0.000) in serum creatinine levels between Healthy group and N.D. Type 2 Diabetics with hypertension group. Significant difference is also noted (P=0.000) in serum creatinine levels between Healthy group and Diabetic Nephropathy group.

                        Group

Mean Difference (I-J)

Std. Error

Sig.

N.D.Type2 Diabetics with Hypertension

N.D.Type2Diabetics

.12948*

0.041

0.000

 Healthy

.21992*

0.031

0.000

Diabetes with Nephropathy

.12083*

0.033

0.000

N.D. Type 2 Diabetics

N.D.Type2Diabetics with Hypertension

-.12948*

0.041

0.000

 Healthy

0.090

0.040

0.161

Diabetes with Nephropathy

-0.009*

0.042

0.000

Healthy

N.D.Type2 Diabetics with Hypertension

-.21992*

0.031

0.000

N.D.Type2Diabetics

-0.090

0.040

0.161

Diabetes with Nephropathy

-.09910*

0.031

0.000

Diabetics with Nephropathy

N.D.Type2Diabetics with Hypertension

-.12083*

0.033

0.000

N.D.Type2Diabetics

0.009*

0.042

0.000

 Healthy

.09910*

0.031

0.000

Table 3. Tukey’s Post Hoc test for Comparison of Serum Creatinine Levels between Healthy, N.D. Type 2 Diabetics, N.D. Type 2 Diabetics with Hypertension and Diabetics with Nephropathy Groups.

*The mean difference is significant at p< 0.05 level. Highly significant at p<0.01 level.

Significant difference (P=0.000) is noted in serum creatinine levels between N.D. Type 2 Diabetics with hypertension and Diabetic Nephropathy Groups.

No significant difference (P=0.161) is noted in Serum Creatinine levels between Healthy group and N.D. Type 2 Diabetics group although slightly higher creatinine levels was noted in N.D. Type 2 Diabetics group (0.988 ± 0.130) than the Healthy group (0.897 ± 0.128).

Discussion

We have observed significantly elevated creatinine levels above the normal range both in N.D. Type 2 Diabetics with hypertension group and in Diabetic Nephropathy group. But we have not observed significantly elevated creatinine levels among N.D. Type 2 Diabetics, unlike other researchers [11-14]. Creatinine levels were well within the normal range in case of N.D. type 2 Diabetics in our study though its level was slightly elevated than that of healthy group. Divya Pandya et al., [17] through their study in North India had reported elevated creatinine levels both in diabetics group and in hypertensive group unlike our report.

The reason may be that our diabetic group is Newly Diagnosed (N.D.) one. Our current study has several strengths. First, this is the first study examining the level of serum creatinine in N.D. type 2 Diabetics with and without hypertension. Moreover, our results provide a comparison of serum creatinine levels for Healthy, N.D.Type 2 Diabetics, N.D.Type 2 Diabetics with hypertension and Diabetics with Nephropathy. In our study, Serum Creatinine levels were increasing from Healthy to N.D. Type 2 Diabetics and then to N.D. Type 2 Diabetics with Hypertension and highest level was seen in Diabetics with Nephropathy. Therefore, our study imparts the clarity regarding changing creatinine patterns in different clinical conditions. Our study has a limitation. Study population is from only one hospital in Bangalore, Karnataka. However, this hospital represents the true population of Karnataka state, South India.

Conclusion

As there were significantly higher serum Creatinine levels noted in N.D. type 2 Diabetics with hypertension group than healthy group and significantly higher Creatinine levels were noted in Diabetic Nephropathy group than N.D. Type 2 Diabetics with Hypertension group, regular monitoring of serum Creatinine levels among Hypertensive Diabetic Individuals is needed to prevent further complications like diabetic nephropathy in them.

Acknowledgements

The authors thank Sri. Krishna Sevashrama Hospital, Bangalore for granting us an opportunity to conduct this study. A special thanks to the Nursing superintendent Mrs. Judith Fernandes for her help in recording the data.

Funding Organizations

The Research received no specific grant from any funding agency in the public, commercial or nonprofit sectors.

Conflict of Interest

The authors have no conflict of interest to declare.

References
1. Zimmet, Paul Z. “Diabetes and its drivers: the largest epidemic in human history?” Clin diabet endocrinol 3.1 (2017): 1.
2. International Diabetes Federation (2017) .IDF Atlas 8th edition.idf.org. Published in 2017. Assessed on October 2018.
3. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001 Dec;414(6865):782-7.
4. Anjana RM, Deepa M, Pradeepa R, Mahanta J, Narain K, Das HK. (2015) Diabetes and Prediabetes in 15 states of India. Annals of Global Health 2015 Nov 1;81(6):830-8.
5. Kaveeshwar SA, Cornwall J. The current state of diabetes mellitus in India. The Australasian Medical Journal. 2014;7(1):45.
6. Babu GR, Murthy GV, Ana Y, Patel P, Deepa R, Neelon SE, et al. Association of obesity with hypertension and type 2 diabetes mellitus in India: A meta-analysis of observational studies. World J Diabet. 2018 Jan 15;9(1):40.
7. Tandon N, Anjana RM, Mohan V, Kaur T, Afshin A, Ong K, et al. The increasing burden of diabetes and variations among the states of India: The Global Burden of Disease Study 1990–2016. The Lancet Global Health. 2018 Dec 1;6(12): e1352-62.
8. Alam R, Verma MK, Verma P. Glycated hemoglobin as a dual biomarker in type 2 diabetes mellitus predicting glycemic control and dyslipidemia risk. Int. J. Life. Sci. Scienti. Res. 2015 Oct;1(2):62-5. 9. Babikr WG, Alshahrani AS, Hamid HG, Abdelraheem AH, Shalayel MH. The correlation of HbA1c with body mass index and HDL-cholesterol in type 2 diabetic patients.
10. DM Vasudevan, ‘Medical Biochemistry’ 8th Edition:374-5.
11. Shrestha S, Gyawali P, Shrestha R, Poudel B, Sigdel M. Serum urea and creatinine in diabetic and non-diabetic subjects. Journal of Nepal Association for Medical Laboratory Sciences P. 2008; 11:12.
12. Richard EJ, Augustine AO, Any CO. Serum urea, uric acid and creatinine levels in diabetic mellitus patients attending Jos University Teaching Hospital, North central Nigeria. International Journal of Biosciences. 2017; 11(4):68-72.
13. Kanwar G, Jain N, Sharma N, Shekhawat M, Ahmed J, Kabra R. Significance of serum urea and creatinine levels in type 2 diabetic patients. IOSR J Dent Med Sci. 2015;14(8):65- 7.
14. Bamanikar SA, Bamanikar AA, Arora A. Study of Serum urea and Creatinine in Diabetic and nondiabetic patients in a tertiary teaching hospital. The Journal of Medical Research. 2016;2(1):12-5. 15. Coresh J, Wei GL, McQuillan G, Brancati FL, Levey AS, Jones C, et al. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Archives of internal medicine. 2001 May 14;161(9):1207-16.
16. Schmieder RE, Veelken R, Gatzka CD, Rüddel H, Schächinger H. Predictors for hypertensive nephropathy: results of a 6-year follow-up study in essential hypertension. Journal of hypertension. 1995 Mar;13(3):357-65
17. Pandya D, Nagrajappa AK, Ravi KS. Assessment and correlation of urea and creatinine levels in saliva and serum of patients with chronic kidney disease, diabetes and hypertension–a research study. Journal of clinical and diagnostic research: JCDR. 2016 Oct;10(10): ZC58.
18. Patel V, Shastri M, Gaur N, Jinwala P, Kadam AY. A study in prevalence of diabetic nephropathy in recently detected cases of type 2 diabetes mellitus as evidenced by altered creatinine clearance, urinary albumin and serum creatinine, with special emphasis on hypertension, hypercholesterolemia and obesity. Int J Adv Med. 2018 Mar 21;5(2):351-2.
19. Hjelmesaeth J, Roislien J, Nordstrand N, Hofsø D, Hager H, Hartmann A. Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a crosssectional study. BMC endocrine disorders. 2010 Dec;10(1):6.
20. Nordin G (2007) Analysis of Hb A/C by particle Enhanced Immunoturbidimetric method.
21. Jung W, Wilke B, Halabi A, Klein G. (2004) Analysis of creatinine in serum by Jaffe’s Method Cli. Chem. Acta 344:137-148.