Hrev_master Healthcare in Low-resource Settings 2024; volume 12:11790 The correlation between creatinine levels and estimated glomerular filtration rate (GFR) with blood glucose levels in diabetes mellitus type 2 patients Ani Riyani,1 Rizka Nerisandi,1 Wiwin Wiryanti,1 Widda Rahmah,2 Nani Kurnaeni1 1Faculty of Medical Laboratory Technologist, Ministry of Health Bandung Health Polytechnic, Bandung; 2Department of Chemical Engineering, Faculty of Industrial Engineering, Bandung Institute of Technology, Bandung, Indonesia Abstract Diabetes mellitus (DM) was a group of metabolic diseases characterized by hyperglycemia. Measuring the blood creatinine level and calculating the estimated glomerular filtration rate (GFR) was crucial in determining if a person had impaired kidney function. These tests provided valuable insights into the progres- sion of type 2 diabetes mellitus and its associated risk of kidney failure. The objective of this study was to investigate the correla- tion between average creatinine levels and GFR with blood glu- cose levels in type 2 DM patients. This correlative research used a cross-sectional approach and included samples from 30 patients with type 2 DM at a hospital in Bandung, Indonesia. The patients’ blood glucose and blood creatinine levels were measured using GFR calculations and a Kenza Max photometer, respectively. The sampling method used was accidental sampling, with the sample criteria being type 2 DM patients who were willing to be respon- dents and did not have hypertension. The average creatinine levels and estimated GFR values were 0.97 mg/dL and 84.971 mL/min/1.73m². The results of the Pearson correlation test indi- cated non-significant correlations (p>0.05, p=0.703 and 0.819). This suggested that there was no significant relationship between creatinine levels and estimated GFR and blood glucose levels in type 2 DM patients. This study provided a foundational explo- ration of the link between blood glucose levels and kidney func- tion, which could contribute to developing methods for examining kidney diseases in type 2 DM patients. This study’s findings underscore the complexity of the relationship between metabolic control and renal function in type 2 diabetes mellitus patients, highlighting the need for individualized patient assessment and management strategies. Introduction One of the major global health concerns is non-communicable diseases (NCDs).1 Diabetes mellitus is a non-communicable dis- ease and poses a serious threat to global health.2,3 Diabetes melli- tus (DM) is a group of metabolic diseases characterized by hyper- glycemia, resulting from deficiencies in insulin secretion, insulin action, or a combination of both. Those with DM are at risk of dysfunction and failure in various organs, including the eyes, kid- neys, nerves, heart, blood vessels and sexual dysfunction.4,5 The prevalence of diabetes has been steadily increasing worldwide in recent years.6 According to the International Diabetes Federation (IDF) in 2021, an estimated 537 million adults (aged 20-79) suffer from DM, and this number is projected to reach 783 million by 2045. It is estimated that over 6.7 million adults will die from dia- betes-related causes in 2021.7 Indonesia is ranked as the country with the fifth-largest number of individuals having DM, with 19.47 million cases. The IDF notes that 80% of people with dia- betes live in low and middle-income countries, and 45% of adults are estimated to remain undiagnosed.7 Generally, the diagnosis of DM is established based on the examination of blood glucose lev- els. DM has several categories, including type 1, type 2, maturity- Correspondence: Ani Riyani, Faculty of Medical Laboratory Technologist, Ministry of Health Bandung Health Polytechnic, Bandung, Indonesia. E-mail: ani_riyanianalis@yahoo.com Key words: blood glucose, creatinine, estimated GFR, Type 2 diabetes mellitus. Contributions: AR, conceptualization, data curation, formal analysis, methodology, validation, visualization, writing – original draft, review & editing; RN, conceptualization, investigation, methodology, validation, and writing – original draft, review & editing; WW, conceptualization, methodology, formal analysis, validation, and writing – original draft, review and editing; NK, methodology, visualization, writing – review & editing; WR, review and editing. Conflict of interest: the authors declare no conflict of interest. Ethics approval and consent to participate: the research has obtained eth- ical approval from the Health Research Ethics Committee at Polytechnic of Health Bandung, as indicated by ethical certificate 40/KEPK/EC/XI/2021. Throughout the research, the researcher adhered to ethical principles, including obtaining informed consent, respecting human rights, ensuring beneficence, and avoiding harm (non-malefi- cence). Patient consent for publication: written informed consent was obtained for anonymized patient information to be published in this article. Funding: this research did not receive external funding. Availability of data and materials: all data generated or analyzed during this study are included in this published article. Received: 13 September 2023. Accepted: 17 November 2023. Early access: 15 December 2023. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2023 Licensee PAGEPress, Italy Healthcare in Low-resource Settings 2024; 12:11790 doi:10.4081/hls.2023.11790 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organi- zations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. [Healthcare in Low-resource Settings 2024;12:11790] [page 29] Non -co mmerc ial us e o nly onset diabetes of the young (MODY), gestational diabetes, neona- tal diabetes, and secondary causes resulting from endocrinopathies, steroid use, etc.8 In general, DM is divided into type I and type 2, with type 2 DM characterized by hyperglycemia due to insulin resistance accompanied by relative insulin deficien- cy.5 Early detection and treatment are beneficial in preventing or delaying the progression of chronic kidney disease (CKD).9 These initiatives encompass a range of strategies, including the provision of health promotion and education activities aimed at raising dia- betes awareness.10 Typically, individuals with diabetes are advised to take anti-diabetic drugs to maintain controlled blood glucose levels, minimizing exposure to chronic hyperglycemia, which can lead to both macrovascular and microvascular complications.11 One of the complications that often occurs in diabetic patients is diabetic nephropathy. Diabetic nephropathy is a diagnosis that refers to specific pathological structural and functional changes observed in the kidneys of patients with DM.12 This complication arises through several mechanisms, such as alterations in renal hemodynamics and the accumulation of advanced glycation end products (AGEs), which can trigger structural kidney damage lead- ing to Chronic Kidney Disease (CKD). CKD is a condition that can necessitate kidney replacement therapy in the form of hemodialy- sis or kidney transplantation.13 One of the manifestations of struc- tural kidney damage is a decrease in the glomerular filtration rate (GFR).14 GFR represents the volume of plasma that the kidneys can clear entirely of specific compounds in one unit of time. Additionally, an indicator to assess kidney damage is a creatinine examination.15 Creatinine results from the endogenous metabolism of skeletal muscle and is excreted through glomerular filtration, ultimately being excreted in the urine without reabsorption by the kidney tubules. The creatinine level is closely related to the esti- mated GFR, which can be calculated by measuring the serum cre- atinine level of the suspected patient using the Modification of Diet in Renal Disease (MDRD) equation. Therefore, estimated GFR and blood creatinine levels are crucial indicators in determin- ing whether a person has impaired kidney function.16 They serve as valuable tools to assess the progression of type 2 diabetes mellitus, which has the potential to lead to kidney failure, and as a means of monitoring kidney function in Type 2 DM patients who have expe- rienced complications of kidney failure.14 The purpose of this study was to determine if there is a rela- tionship between the average creatinine level and the estimated GFR with blood glucose levels in type 2 diabetes mellitus patients, by determining the average creatinine level and the esti- mated GFR value. Materials and Methods Study design This study was a correlational study with a cross-sectional design aimed at determining the relationship between creatinine levels and estimated GFR on blood glucose levels in type 2 DM patients. The study was conducted at a hospital in Bandung, Indonesia, from October to November 2021. Patients The sampling technique used in this study was accidental sam- pling, wherein samples were collected from the serum of patients with type 2 DM who visited the hospital laboratory. Inclusion criteria Type 2 diabetic patients who are over 30 years old, have fast- ing blood glucose levels higher than 126 mg/dL, and have given their consent to participate in the study. Exclusion criteria Individuals with a history of hypertension and kidney failure were not included in the study. Examination of blood glucose GOD-PAP methods Glucose is oxidized by GOD to gluconic acid and hydrogen peroxide, which, in conjunction with POD, reacts with chloro-4- phenol and PAP to form a red quinoneimine. The absorbance of the colored complex, proportional to the concentration of glucose in the specimen, is measured at a 500 nm wavelength (Figure 1). GOD oxidizes glucose to gluconic acid and hydrogen peroxide, which, in conjunction with POD, reacts with chloro-4-phenol and PAP to form a red quinoneimine. The absorbance of the colored complex, proportional to the concentration of glucose in the spec- imen, is measured at a 500 nm wavelength. All measurements were conducted at room temperature. Examination of creatinine serum Jaffe Reaction methods The colorimetric reaction (Jaffe reaction) of creatinine with alkaline picrate was measured kinetically at 490-510 nm without any pre-treatment step. This reaction has been improved in terms of specificity, speed, and adaptability by developing an initial-rate method. The measurements were conducted at room temperature (Figure 2). Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions Figure 1. Procedure for quantitative determination of blood glu- cose GOD-PAP method. Figure 2. Procedure for quantitative determination of creatinine serum Jaffe Reaction method. [page 30] [Healthcare in Low-resource Settings 2024;12:11790] Non -co mmerc ial us e o nly Estimation of GFR with Cockcroft-Gault formula based on SCr The Cockcroft-Gault equation was used to estimate the GFR value from known variables such as serum creatinine (mg/dL), age (years), and body weight (kg) based on Equation 1 for males and Equation 2 for females.17 (eq. 1) (eq. 2) Statistical analysis The measured creatinine level, estimated GFR, and blood glu- cose level dataset were subjected to bivariate analysis, specifically the Pearson correlation test. The Pearson correlation coefficient provides a measure of the correlation between two variables, using a scale ranging from -1 to +1, where 0 indicates no linear or mono- tonic relationship. As the coefficient approaches an absolute value of 1, the association becomes stronger, moving closer to a straight line. It’s important to note that the Pearson correlation coefficient should not be confused with linear regression. The Pearson corre- lation coefficient is used when both variables are observed values subject to natural random variation, such as in the accidental sam- pling method. Conversely, in linear regression, the values are dependent on a variable that is chosen and set as a constant in an experimental protocol. The basic decision-making process in the Pearson Correlation test is as follows: if the Significance (Sig) value is <0.05, then there is a correlation; if the Significance (Sig) value is >0.05, then there is no correlation Results Creatinine levels of the type 2 diabetes mellitus patients Based on Table 1, the frequency distribution of 30 patients with Type 2 DM shows that two patients (6.7%) had low creatinine levels, 18 patients (60%) had normal creatinine levels, and ten patients (33.3%) had high creatinine levels. The average creatinine level in Type 2 DM patients was 0.97 mg/dL. Table 2 presents the distribution of 30 patients with type 2 DM based on gender, age, and the duration of DM they have suffered. Among the female patients (70.0%), two patients (6.7%) had low creatinine levels, ten patients (33.3%) had normal creatinine levels, and nine patients (30.0%) had high creatinine levels. In contrast, among the male patients, nine (30%), eight (26.7%), and one (3.3%) had low, normal, and high creatinine levels, respectively. The research conducted on 30 patients with Type 2 DM, aged 31-82 years, revealed three categories of results in serum creati- nine levels: low, normal, and high. It was observed that ten indi- viduals had high creatinine levels, predominantly in the age group of 60-69 years, with as many as eight patients (26.6%). Furthermore, the study, conducted on 30 patients with type 2 DM, was mainly composed of patients who had suffered from type 2 DM for 6-10 years, totaling 17 patients. The examination of serum creatinine levels yielded three categories: low, normal, and high. It was found that one person (3.3%) had low creatinine lev- els, eight people (26.7%) had normal creatinine levels, and eight people (26.7%) had high creatinine levels. Eight patients had been living with DM for 0-5 years, while eight patients had been dealing with DM for more than 10 years. Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions Table 2. Frequency distribution of creatinine levels in type 2 diabetes mellitus patients based on gender, age, and duration of diabetes mellitus. Creatinine levels in type 2 diabetes mellitus patients (mg/dL) Low Normal High Frequency N % N % N % N % Gender Male 0 0 8 26.7 1 3.3 9 30.0 Female 2 6.7 10 33.3 9 30 21 70.0 Total 2 6.7 18 60.0 10 33.3 30 100 Age 30-39 years old 0 0 2 6.7 0 0 2 6.7 40-49 years old 1 3.3 3 10.0 0 0 4 13.3 50-59 years old 0 0 6 20.0 0 0 6 20.0 60-69 years old 1 3.4 4 13.3 8 26.6 13 43.3 >70 years old 0 0 3 10.0 2 6.7 5 16.7 Total 2 6.7 18 60.0 10 33.3 30 100 Duration of diabetes mellitus 0-5 years 0 0 5 16.7 0 0 5 16.7 6-10 years 1 3.3 8 26.7 8 26.7 17 56.7 >10 years 1 3.4 5 16.6 2 6.6 8 26.6 Total 2 6.7 18 60 2 33.3 30 100 Table 1. Frequency distribution of creatinine levels in type 2 diabetes mellitus patients. Creatinine levels in type 2 diabetes mellitus patients (mg/dL) Variable Low Normal High Frequency Mean N % N % N % N % Creatinine levels in type 2 2 6.7 18 60 10 33.3 30 100 0.97 diabetes mellitus (mg/dL) [Healthcare in Low-resource Settings 2024;12:11790] [page 31] Non -co mmerc ial us e o nly Estimation of glomelurus filtration rate of the type 2 diabetes mellitus patients Based on Table 3, after analyzing the frequency distribution of 30 patients with type 2 diabetes mellitus, it was determined that normal GFR values were found in 15 patients with type 2 diabetes mellitus (50.0%), while an estimated mild GFR value was observed in nine patients (30.0%). The average estimated GFR value in type 2 diabetes mellitus patients was 84.971 mL/min/1.73m². Table 4 explains the frequency distribution of estimated GFR values for 30 patients with type 2 DM, the majority of whom were females (21 patients, 70%). Among the 21 female patients, nine (30%) had estimated GFR values in the normal cat- egory, six (20%) in the mild category, and the remaining six (20%) in the moderate category. For the males, there were nine patients (30%) with estimated GFR values in the normal category, six (20%) in the mild category, and six (10%) in the moderate catego- ry. After analyzing the frequency distribution of 30 patients with Type 2 DM, within an age range of 31-82 years, it was observed that the age group of 60-69 years was the most dominant, compris- ing 13 patients (43.4%). Among these patients, 13 had estimated GFR values in the normal category, three (10.0%) in the mild cat- egory, and five (16.7%) had moderate GFR values. Among the 30 patients with type 2 DM, the analysis revealed that the majority had a long history of having type 2 DM for 6-10 years. Seventeen patients (56.6%) had estimated GFR values in the normal category, seven (23.4%) in the mild category, and five (16.6%) in the mod- erate category. Pearson correlation test results The results of the Pearson correlation analysis are tabulated in Table 5. The Pearson correlation between blood glucose levels and creatinine levels is of a negative value (r =-0.730), indicating an inversely linear relationship. However, the correlation between blood glucose levels and the estimated GFR values is 0.044, which is close to 0, suggesting no linear relationship. Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [page 32] [Healthcare in Low-resource Settings 2024;12:11790] Table 3. Frequency distribution of glomelurus filtration rate in type 2 diabetes mellitus patients. Estimation of GFR in type 2 DM patients (mL/min/1.73m2) Variable Normal Mild Moderate Severe Chronic Mean N % N % N % N % N % Estimation of GFR in type 2 15 50.0 9 30.0 6 20.0 0 0 0 0 84.971 diabetes mellitus (mL/min/1.73m2) GFR, glomelurus filtration rate. Table 4. Frequency distribution of glomelurus filtration rate in type 2 diabetes mellitus patients based on gender, age, and duration of DM diagnosis. Estimation of glomelurus filtration rate in type 2 diabetes mellitus patients based on gender (mL/min/1.73m2) Normal Mild Moderate Severe Chronic Frequency N % N % N % N % N % N % Gender Male 6 20 3 10 0 0 0 0 0 0 9 30 Female 9 30 6 20 6 20 0 0 0 0 21 70 Total 15 50 9 30 6 20 0 0 0 0 30 100 Age 30-39 years 2 6.7 0 0 0 0 0 0 0 0 2 6.7 40-49 years 3 10.0 1 3.3 0 0 0 0 0 0 4 13.3 50-59 years 4 13.3 2 6.7 0 0 0 0 0 0 6 20.0 60-69 years 3 10.0 5 16.7 5 16.7 0 0 0 0 13 43.4 70-82 years 3 10.0 1 3.3 1 3.3 0 0 0 0 5 16.6 Total 15 50.0 9 30.0 6 20.0 0 0 0 0 30 100 Duration of diabetes mellitus 0-5 years 3 10 2 6.7 0 0 0 0 0 0 5 16.7 6-10 years 7 23.4 5 16.6 5 16.6 0 0 0 0 17 56.6 >10 years 5 16.6 2 6.7 1 3.4 0 0 0 0 8 26.7 Total 15 50.0 9 30.0 6 20.0 0 0 0 0 30 100 Table 5. The pearson correlation test results. Fasting glucose level Creatinine level Glomelurus filtration rate Fasting glucose level Pearson correlation (r) 1 - 0.073 0.044 Sig. (2-tailed) - 0.703 0.819 N 30 30 30 Creatinine level Pearson correlation (r) -0.073 1 -0.863 Sig. (2-tailed) 0.703 - 0.000 N 30 30 30 Glomelurus filtration rate Pearson correlation (r) 0.044 -0.863 1 Sig. (2-tailed) 0.819 0.000 - N 30 30 30 Non -co mmerc ial us e o nly Discussion Among the 30 respondents with type 2 DM, more than half of them (60.0%) exhibited normal creatinine levels. Among the remaining respondents, 33.3% showed high creatinine levels, and 6.7% exhibited low creatinine levels. These results align with a study conducted by Dedi in 2020 on 174 type 2 DM patients, which found high creatinine levels in 40.2% of cases, normal cre- atinine levels in 44.2% of cases, and low creatinine levels in 15.5% of cases. Another study by Kurniawan reported that 55 type 2 DM patients had high creatinine levels in 83.6% of cases and normal creatinine levels in 16.4% of cases.18,19 In this study, several cases of high glucose levels were fol- lowed by high creatinine values. In patients with type 2 diabetes mellitus, high glucose levels can damage the kidney filters over time, affecting kidney function and increasing blood creatinine levels. Several factors can lead to normal creatinine levels in type 2 DM patients in this study. One such factor is age. The study’s age range was 31-82 years, with normal creatinine levels in 18 people (60.0%), most notably in the age range of 60-69 years. This indi- cates that the respondents’ kidney function was still healthy and undamaged. Normal creatinine levels are generally maintained at a constant rate, and levels above the normal range indicate impaired kidney function.20 Other factors that affect creatinine levels include blood glucose levels and the duration of type 2 DM. Elevated blood glucose lev- els weaken and make the blood vessel walls more brittle, leading to blockages in small blood vessels, resulting in microvascular complications such as nephropathy. Additionally, based on the esti- mated GFR value in type 2 DM patients, there were six individuals in the moderately reduced kidney function category, nine in the mildly decreased kidney function category, and 15 with normal kidney function. The estimation of GFR values in type 2 DM patients can be associated with several factors, including the dura- tion of having type 2 DM, which is linked to the risk of DM com- plications. The main factor triggering complications in type 2 dia- betes mellitus is not only the duration but also the severity of DM. However, when balanced with a healthy lifestyle, it can lead to a better quality of life that helps prevent complications.21 This aligns with the results of research that has shown that patients having type 2 DM for 6-10 years can have five individuals in the moderate category, indicating the beginning of kidney dam- age and decreased kidney function. In contrast, among other respondents with the same duration of DM, the average GFR was in the mild category, indicating indications of kidney damage but still maintaining normal kidney function. This illustrates that, among type 2 DM patients with a long duration of 6-10 years, many continue to lead a healthy lifestyle. Another factor that can influence the GFR value is increased creatinine levels. Creatinine and GFR values are inversely propor- tional, where higher serum creatinine values correspond to lower GFR values. The results of this study indicate that GFR values can be used to monitor the progression of type 2 DM, which has the potential to lead to kidney problems (diabetic nephropathy).22–24 Bivariate analysis of the measured creatinine levels, estimated GFR, and blood glucose levels using Pearson correlation tests revealed that there was no significant relationship between creati- nine levels (Sig. 0.703, p>0.05) and estimated GFR (Sig. 0.819, p>0.05) with blood glucose levels among the 30 type 2 DM patients. Conclusions This study indicates that high blood glucose levels do not nec- essarily correspond to high creatinine levels or low estimated GFR values. It also suggests that not all type 2 DM individuals with ele- vated blood glucose will experience kidney impairment. To strengthen this conclusion, additional research should incorporate HbA1C values, which serve as an indicator of well-managed blood sugar levels in type 2 DM patients. References 1. 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