Biomedical Research

Abstract

An association between urinary albumin excretion and an increased incidence of diabetes mellitus (DM) has already been demonstrated. However, the prevalence of microalbuminuria (MA) in Type 2 diabetes mellitus (T2DM) Thai patients, especially in the northeastern part of Thailand, has not been reported. We, therefore, aimed to conduct a cross-sectional study to investigate the prevalence of urinary albumin excretion in T2DM patients at Nong Wua Saw Hospital, Udon Thani Province, Thailand. A total of 1,025 T2DM patients were enrolled in this study. Spot morning urine samples were screened for elevated urinary albumin excretion (UAE). Positive UAE screening tests were further analyzed for a quantitative measurement of albuminuria. The mean and standard deviation (SD) of the population age was 61.35 ± 10.97 years. The overall prevalence of albuminuria was 33%. The prevalence of macroalbuminuria and MA was 33.3% and 38%, respectively. The demographic profiles and MA showed that T2DM patients at an age>60 years old were found with MA more frequently than those at an age ≤60 years old by up to 1.5-fold (p-value=0.001, OR (95% CI)=1.53 (1.19-1.97)). Moreover, female patients with DM had a higher level of MA than male patients (p-value=0.002, OR (95% CI)=0.67 (0.51-0.88)). The present study showed that the prevalence of MA among T2DM patients was 38%. Age and gender were risk factors for the development of MA. Early detection and awareness of these factors can improve patient prognosis and reduce the burden of overt DM nephropathy in future studies.

Keywords

Microalbuminuria, Diabetes mellitus, Northeastern part of Thailand.

Introduction

Coronary Diabetes mellitus (DM) consists of two types including Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). T1DM or insulin-dependent diabetes mellitus (IDDM) is a form of diabetes in which very little or no insulin is produced by the pancreas. It used to be called juvenile-onset diabetes because it usually develops at a young age. T2DM or non-insulin-dependent diabetes mellitus (NIDDM) is a chronic disease. It is characterized by high levels of sugar in the blood, insulin resistance, and a relative lack of insulin. T2DM also used to be called adult-onset diabetes because it used to start almost always in middle- and late-adulthood [1]. T2DM has emerged as the new pandemic of the 21^st century, and it is estimated that 80% of people with diabetes live in low- and middle-income countries [2]. It is also estimated that there were 415 million people with T2DM worldwide in the year 2015, and the number of people with diabetes aged 20-79 years is predicted to rise to 642 million people by 2040 [3]. More than 60% of patients with T2DM live in Asia, with almost one-third in China [4]. Thailand is among the countries in Asia with a high prevalence of T2DM [5]. T2DM continues to grow in the Thai population from the year 2013 to 2035 [6]. Among the 200,000 deaths annually among the Thai population with chronic non-communicable diseases, about 30,000 deaths are attributed to T2DM [7].

T2DM is the leading cause of end-stage renal disease worldwide [8]. Microalbuminuria (MA) has been established as an early marker of both diabetic nephropathy and vascular disease in patients with diabetes mellitus (DM) [9,10]. MA is one of the early markers not only of diabetic nephropathy but also of cardiovascular disease morbidity and mortality in patients with diabetes [11,12]. The presence of MA in the urine of persons with T2DM is perhaps the most important early signal heralding the onset of systemic vasculopathy, and it is associated with target organ damage such as the brain, heart, and kidneys [13-15]. A study in the north-eastern region of Thailand demonstrated that the highest prevalence of T2DM in Thailand was found there [16]. Specifically, UdonThani Province in the north-eastern part of Thailand has the largest number of diabetic subjects. Therefore, the study of MA among patients with DM in that province is essential to assess the burden of diabetes. In the present study, the prevalence of microalbuminuria and macroalbuminuria among Type 2 diabetic patients being attended to at diabetescentre in NongWua Saw Hospital, Udon Thani Province, Thailand, was explored.

Materials and Methods

Samples

Patients who were diagnosed with T2DM and being attended to at Nong Wua Saw Hospital, Udon Thani Province, from January to December 2018 were enrolled in the present study. T2DM was diagnosed based on the World Health Organization (WHO) study group report criteria [17].

Data collection

The retrospective data of patients with T2DM including their age and gender were collected and extracted. The protocol of this study was approved by the NongWua Saw Hospital and the Ethical Clearance Committee on Human Rights related to researches involving human subjects of Walailak University (EC number). Informed consent was not obtained since this research was a retrospective study. The data files of patients were kept in a file with a password in order to protect the privacy of patients. The names and ID numbers for each patient were removed from the files before data analysis.

Laboratory assays

The screening for elevated urinary albumin excretion (UAE) was tested by "protein error of indicators" dipstick: CYBOW^® urine reagent strip (DFI Co., Ltd. (Korea)). All patients gave a spot morning urine sample for analysis, and it was reported as negative or positive (at least 20 mg/L). Urine samples from participants who reported positive from the CYBOW test were then sent for a quantitative measurement of albuminuria. Albuminuria was measured as urine albumin concentration (UAC) by the method of the immunoturbidimetric technique with a Randox RX Imola Chemistry Analyzer (Randox Laboratories Ltd, United Kingdom). Category spot was defined as follows: (1) normoalbuminuria was defined as less than 30 mg/g creatinine, (2) microalbuminuria was defined as 30-300 mg/g creatinine, and (3) macroalbuminuria was defined as albumin-to-creatinine ratio (ACR) more than 300 mg/g creatinine.

Statistical analysis

Data analysis was performed to calculate frequency and data distribution by SPSS Software, Version 11.5 for Windows. The normality of data was evaluated by the Kolmogorov-Smirnov test. Data was described and analyzed with a parametric test, or a non-parametric test for non-normally distributed parameters. MA level was evaluated for association with a patient’s general characteristics using the Chi2-test. The level of type I error was α=5%, and p-value < 0.05 was considered significant.

Results

General characteristics

Among the 1,025 T2DM patient cases retrieved from Nong Wua Saw Hospital, 321 cases (31.3%) included male patients whereas 704 cases (68.7%) included female patients. The demographic data of patient characteristics is shown in Table 1. The mean and SD of the population age was 61.35 ± 10.97 years. The overall prevalence of albuminuria was 33%. The prevalence of macroalbuminuria and MA was 512 cases (33.3%) and 389 cases (38%), respectively.

Table 1: Patient characteristics included in the study.

Demographic profiles and microalbuminuria

Age was categorized as˃60 years or ≤60 years with the mean age around 60 years, following the study by Stamm et al. [18]. T2DM patients at an age>60 years old were found with MA more frequently than those at an age ≤ 60 years old by up to 1.5-fold (p-value=0.001, OR (95% CI)=1.53 (1.19-1.97)). Moreover, female patients with DM had a higher level of MA than male patients (p-value=0.002, OR (95% CI)=0.67 (0.51-0.88)) (Table 2).

Table 2: Association between age, gender, and microalbuminuria.

Discussion

The present study was the first to report the prevalence of MA in T2DM patients at the NongWua Saw Hospital, UdonThani Province, Thailand. A prevalence of MA was exhibited among 38% of the patients with T2DM who were being attended to at a diabetic clinic in NongWua Saw Hospital. Our study showed the association between age and the presence of MA. An older age was associated with MA because of the longer duration of DM. The results were similar to those results of other previous studies [19,20]. The possible explanation for this finding was that the prevalence of MA increased significantly with the increasing numbers of metabolic syndrome, a cluster of metabolic disorders including insulin resistance, obesity, atherogenic dyslipidemia, and hypertension, which are frequently found in the elderly population [21,22].

The present study found that female patients with DM had a significantly positive correlation with MA. This result was similar to another previous study [23]. It can be explained by some researches, which showed that there are more women than men with diabetes, especially in developed countries [24]. Similarly in Thailand, the overall prevalence of diabetes in Thai adults aged ≥ 20 years was 9.9%, with a higher prevalence among women (10.8%) than men (8.9%) [25]. Moreover, Thai women were estimated to be overweight by more than 10% when compared to Thai men [26]. This may be the cause of DM, which was associated with the differential level of MA in both sexes.

There were some limitations in our study. Firstly, there was a small sample size. Secondly, the measurement of MA was performed only once, which did not match with the definition of the MA test. Nevertheless, the results of the present study provided evidence of MA in patients with DM. Moreover, the correlation between the characteristics of patients with DM and the level of MA among the Thai population was also revealed in the present study.

Conclusion

In conclusion, MA is common in DM Thai patients. Patients at an older age were associated with an increased level of MA. In addition, female patients had a higher level of MA than male patients. The detection of MA in patients can be useful for the screening of DM during annual health check-ups. Moreover, MA may be adopted as a marker among patients with T2DM. The results of the present study will help optimize care and reduce the burden of overt DM nephropathy in future studies.

Acknowledgement

The authors are grateful to and would like to specifically thank Mr. Dave Chang for language editing of this article.

References

1. Harreiter J, Roden M. Diabetes mellitus-Definition, classification, diagnosis, screening and prevention. leitlinien für die praxis 2019; 131: 6-15.
2. Ginter E, Simko V. Type 2 diabetes mellitus, pandemic in 21st century. Adv Exp Med Biol 2012; 771: 42–50.
3. Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017; 128: 40-50.
4. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103: 137-149.
5. Nanditha A, Ma RC, Ramachandran A, Snehalatha C, Chan JC, Chia KS, Shaw JE, Zimmet PZ. Diabetes in Asia and the Pacific: Implications for the Global Epidemic. Diabetes Care 2016; 39: 472-485.
6. International Diabetes Federation. IDF Diabetes Atlas Sixth Edition. 2013.
7. Porapakkham Y, Rao C, Pattaraarchachai J, Polprasert W, Vos T, Adair T, Lopez AD. Estimated causes of death in Thailand, 2005: implications for health policy. Popul Health Metr. 2010; 8:14.
8. Cordonnier D, Bayle F, Benhamou PY, Milongo R, Zaoui P, Maynard C, Halimi S. Future trends of management of renal failure in diabetics. Kidney Int Suppl 1993; 41:S8-13
9. Afkarian M, Zelnick LR, Hall YN. Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014. JAMA 2016; 316: 602-610.
10. De Boer IH, Gao X, Cleary PA. Albuminuria changes and cardiovascular and renal outcomes in type 1 diabetes: the DCCT/EDIC Study. Clin J Am Soc Nephrol 2016; 11: 1969-1977.
11. Persson F, Rossing P. Diagnosis of diabetic kidney disease: state of the art and future perspective. Kidney Int Suppl 2018; 81: 2-7.
12. Lau AC, Lo MK, Leung GT, Choi FP, Yam LY, Wassermann K. Altered exercise gas exchange as related to microalbuminuria in type 2 diabetic patients. Chest 2004; 125: 1292-1298.
13. Xu RS. Pathogenesis of diabetic cerebral vascular disease complication. World J Diabetes 2015; 6: 54-66.
14. Zanella MT. Microalbuminuria: cardiovascular and renal risk factors underestimated in clinical practice. Arq Bras Endocrinol Metabol 2006; 50: 313-321. 
15. Cooper ME, Bonnet F, Oldfield M, Jandeleit-Dahm K. Mechanisms of diabetic vasculopathy: an overview. Am J Hypertens 2001; 14: 475-486.
16. Aekplakorn W, Abbott-Klafter J, Premgamone A, Dhanamun B, Chaikittiporn C, Chongsuvivatwong V, Suwanprapisa T, Chaipornsupaisan W, Tiptaradol S, Lim SS. Prevalence and management of diabetes and associated risk factors by regions of Thailand: Third National Health Examination Survey 2004. Diabetes Care 2007; 30.
17. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabetic Med 1998; 15: 539-53.
18. Stamm AM, Meinerz G, Silva JC. Systemic hypertension and microalbuminuria. Arquivos brasileiros de cardiologia 2007; 89: 415-420.
19. Ruilope LM, Segura J. Predictors of the evolution of microalbuminuria. Hypertension 2006; 48: 832-833.
20. Chowta NK, Pant P, Chowta MN. Microalbuminuria in diabetes mellitus: Association with age, sex, weight, and creatinine clearance. Indian J Nephrol 2009; 19: 53-56.
21. Metcalf P, Baker J, Scott A, Wild C, Scragg R, Dryson E. Albuminuria in people at least 40 years old: Effect of obesity, hypertension, and hyperlipidemia. Clin Chem 1992; 38:1802-1808.
22. Li XH, Lin HY, Wang SH, Guan LY, Wang YB. Association of Microalbuminuria with Metabolic Syndrome among Aged Population. Biomed Res Int 2016; 2016.
23. Buranakitjaroen P, Deerochanawong C, Bunnag P. Microalbuminuria prevalence study (MAPS) in hypertensive patients with type 2 diabetes in Thailand. J Med Assoc Thai 2005; 88: 1624-1629.
24. King H, Aubert R, Herman W: Global Burden of Diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21:1414-1431.
25. Aekplakorn W, Chariyalertsak S, Kessomboon P, Assanangkornchai S, Taneepanichskul S, Putwatana P. Prevalence of Diabetes and Relationship with Socioeconomic Status in the Thai Population: National Health Examination Survey, 2004-2014. Journal of diabetes research, 2018; 1654530.
26. Aekplakorn W, Mo-Suwan L. Prevalence of obesity in Thailand. Obes Rev 2009; 10: 589-592.