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Diabetes & Obesity International Journal Research Article 12 min read

Increased Triglycerides and High Density Lipoprotein Ratio Associated with Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Sengsuk J1 Tangvarasittichai O2 and Tangvarasittichai S2*
* Corresponding author
ISSN: 2574-7770  10.23880/doij-16000166  Received: September 13, 2017  Published: October 22, 2017
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Keywords
Type 2 Diabetes Mellitus Estimated Glomerular Filtration Rate Chronic Kidney Disease Hypertriglyceridemia Reduced High Density Lipoprotein Cholesterol
Abstract

Dyslipidemia is a common occurrence in type 2 diabetes mellitus (T2DM) patients and plays the major role in accelerated risk of cardiovascular disease (CVD) and possible causes chronic kidney disease (CKD), the progression of which leads to end-stage renal disease. A total of 266 T2DM patients were categorized into 2 groups according to their TG/HDL-C ratio of 2.5 and

Introduction

Dyslipidemia is common in patients with type 2 diabetes mellitus (T2DM) and it plays the major role in the accelerated risk of cardiovascular disease (CVD) in those patients [1, 2, 3]. Elevated triglycerides (TG) reduced high density lipoprotein cholesterol (HDL-C) and small dense low density lipoprotein (LDL)-particles (independent of LDL-cholesterol (LDL-C)), elevated triglyceride-rich remnant lipoprotein (TGRLs), and hyperinsulinemia [1, 2, 3] are the major clinical characteristics of dyslipidemia in T2DM patients. Lower HDL-C level is associated with insulin resistance for mediated glucose disposal and compensation of hyperinsulinemia, with high levels of fasting glucose and insulin [4]. Chronic kidney disease (CKD) is defined as the insufficiency or reduction in the glomerular filtration rate (GFR) as well as the abnormalities of structure and/or function of the kidneys as evidenced by urinalysis, biopsy or imaging [5, 6]. CKD is the one of the global public health concerns and the major risk factor of cardiovascular disease. CKD in T2DM patients contributes the morbidity, mortality and excessive health care [7]. Moreover, cardiovascular death in T2DM patients has been shown to be associated with the development of CKD and progression to end-stage renal disease (ESRD) [8, 9, 10]. CKD progression leads to ESRD that needs treatment with dialysis and causes accelerated morbidity and mortality in T2DM patients [11, 12, 13]. Dyslipidemia has been implicated as a possible cause of CKD [14, 15]. Many researchers have demonstrated the association of moderate CKD with elevated levels of triglycerides (TG) and a decreased level of high density lipoprotein cholesterol (HDL-C) ratio [14, 15, 16, 17]. Among others, our recent studies have also demonstrated that TG/HDL-C ratio was associated with insulin resistance [13, 18, 19, 20]. The TG/HDL-C ratio was a better predictor of both cardiovascular events and the LDL particle size [18, 19, 20]. However, there is little knowledge about the association of TG/HDL-C ratio and CKD. In the present study, we aim to evaluate the association of TG/HDL-C with CKD in T2DM patients.

Materials and Methods

Subjects

A total of 266 T2DM patients were randomized from the Diabetes Care Clinic of Ladyao Hospital, Nakornsawan Province during December 2013 to July 2014. All T2DM patients had overt diabetes for more than 5 years. They were receiving regular treatment with glycemic lowering, lipid lowering and anti- hypertensive medication. The exclusion criteria were sustained heart failure, recent myocardial infarction, unstable angina, stroke, ESRD, acute or chronic infection, cancer, hepatic disease and acute illness. They had good history of control over their blood glucose levels at time of recruitment. All participants gave written informed consent. Our study protocol was approved by the Ethic committees of Naresuan University.

Physical and Biochemical Examination

Blood pressure (BP) measurement, height, weight and waist circumference (WC) were measured and body mass index (BMI) was calculated for all T2DM patients. WC was measured at the midpoint between the rib cage and the top of lateral border of iliac crest at minimum respiration. BP was measured after the participants had been seated and rested for 5 minutes and the mean value of at least two measurements was used. Venous blood samples were collected in the seated position from all participants without stasis after 8–12 hour fast. Blood specimens were processed and assayed in the clinical laboratory of Ladyao Hospital, Nakornsawan Province, Thailand. Plasma glucose (Glu), blood urea nitrogen (BUN), creatinine (CT), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and hemoglobin A1c (HbA1c) were measured by with standard enzymatic method (Thermo Scientific, KONELAB Prime 60i, Finland). TG/HDL-C ratio was calculated by TG divided by HDL-C concentrations (expressed as mg/dl).

Estimated Glomerular Filtration Rate (Egfr)

Estimated glomerular filtration rate was calculated by the Cockroft–Gault formula which incorporates age, body weight, and sex [21]. The formula is: eGFR = [(140 - age) * weight (kg) *constant]/[serum creatinine (µmol/L)] where 1.23 and 1.04 are constants for men and women, respectively. Five eGFR stages were used: Stage I was normal eGFR (≥90ml/min/1.73 m2); Stage II was mild eGFR (60-89 mL/min/1.73 m2); Stage III was moderate eGFR (30-59 ml/min/1.73 m2); Stage IV was severe eGFR (<30 ml/min/ 1.73 m2), and Stage V was end-stage renal disease: eGFR (<15 ml/min/1.73 m2). An eGFR lower than 60 ml/min/1.73 m2 (moderately eGFR) was defined as chronic kidney disease (CKD) [12].

Statistical Analysis

All data are presented as median and inter quartile range for non-normally distributed data and tested with Shapiro-Wilk test. These T2DM patients were stratified to 2 groups according to TG/HDL-C ratio ≥2.5 and <2.5 as in our recent study [17]. We compared all clinical characteristics of these 2 groups of T2DM patients by using Mann-Whitney U-test. Bivariate correlation of these clinical variables was analyzed by using Spearman rank correlation test. Clinical variables that correlated with TG/HDL-C ratio in these T2DM patients were tested as independent variables in multivariate analysis. Odds ratios (OR) from logistic regression analyses were used to estimate the risk of CKD. Elevated TG/HDL-C ratio was associated with CKD and elevated HbA1c after adjusting with their covariate. The results of all statistical analyses were evaluated for statistical significance using p-value <0.05 and the 95% confidence intervals (CI). All analysis was performed using the SPSS computer program version 13.0 (SPSS, Chicago, IL).

Results

The comparison results of these two groups demonstrated that T2DM patients with higher TG/HDL- C ratio group was significantly higher Glu, HbA1c, TC, TG, LDL-C levels and lower HDL-C, eGFR levels (p<0.05) as shown in Table 1. The medication of glycemic lowering and lipid lowering are also listed in Table 1. The bivariate correlation of TG/HDL-C ratio with eGFR (r= -0.496, p<0.001), HbA1c (r= 0.138, p=0.024), Glu (r= 0.194, p=0.002), TC (r= 0.178, p=0.004), and SystBP (r= 0.201, p=0.014), while the bivariate correlation of the other variables are shown in Table 2. By multiple logistic regression analysis, elevated TG/HDL-C ratio Variables TG/HDL-C ≥ 2.4 Age (yrs) 63.0* (55.0-72.0)* 63.0 (51.5-71.0) 0.370 Glu (mmol/l) 7.12 (6.07-8.91) 6.60 (5.39-7.92) 0.013 HbA1c 54.70 (49.15-61.72) 51.74 (45.83-60.24) 0.022 BUN (mmol/l) 4.99 (3.92-6.78) 4.99 (3.92-6.78) 0.966 CT (μmol/l) 76.91 (60.11-99.45) 73.37 (56.58-97.59) 0.167 TC (mmol/l) 4.64 (4.02-5.39) 4.26 (3.65-4.82) 0.003 TG (mmol/l) 1.93 (1.54-2.64) 1.01 (0.83-1.19) <0.001 HDL-C (mmol/l) 1.01 (0.88-1.22) 1.53 (1.32-1.83) <0.001 LDL-C (mmol/l) 2.56 (2.09-3.28) 2.19 (1.69-2.88) 0.002 TG/HDL-C ratio 4.10 (3.15-6.60) 1.60 (1.10-2.00) <0.001 eGFR (ml/min/1.73 m2) 59.0 (50.24-82.27) 83.80 (62.94-98.39) <0.001 Metformin 138(71.5%) 50(68.5%) Triglycerides level (≥1.70 mmol/l) 130(67.4%) - Triglycerides level (<1.70 mmol/l) 63(32.6%) 73(100%) HDL-C levels (≤1.04 mmol/l men, ≤1.30 mmol/l women) 143(74.1%) 14(19.2%) HDL-C levels (>1.04 mmol/l men, >1.30 mmol/l women) 50(25.9%) 59(80.8%) Glipizide 90(46.6%) 35(47.9%) Pioglitazone 19(9.8%) 6(8.2%) Glibencamide 6(3.1%) - Mixtard 7(3.6%) 2(2.7%) Simvastratin 123(63.7%) 35(47.9%) Gemfibrozil 36(18.7%) 4(5.5%) Atovastatin 3(1.6%) 1(1.4%) was associated with risk of CKD, OR 4.21 (95 % CI 2.13- 8.33) and elevated HbA1c, OR 2.47 (95 % CI 1.23-4.95) after adjusting for covariates in these T2DM patients, as demonstrated in Table 3.

Correlation betweenCorrelation coefficientCorrelation betweenCorrelation coefficient
parametersrp- valueparametersrp- value
AgeBUN-0.498<0.001TGHDL-C-0.460<0.001
CT-0.347<0.001LDL-C0.1340.032
eGFR-0.2220.006WC0.2120.018
GluCT-0.1990.001HDL-CHbA1c-0.1440.018
TG0.1770.004TG/HDL-CeGFR-0.496<0.001
HDL-C-0.1850.003Glu0.1940.002
LDL-C0.1300.037HbA1c0.1380.024
HbA1c0.510<0.001SystBP0.2010.014
WC0.2410.004HDL-C-0.786<0.001
BUNCT0.622<0.001TG0.907<0.001
eGFR-0.462<0.001TC0.1780.004
SystBP0.2100.012eGFRTC-0.498<0.001
CTeGFR-0.643<0.001TG-0.347<0.001
HDL-C-0.1360.027HDL-C-0.2220.006
TCTG0.322<0.001SystBP0.2240.008
HDL-C0.1270.038
LDL-C0.901<0.001
DiastBP0.2040.022

Table 1: Bivariate correlation of the variables in these type 2 diabetes patients.

VariablesElevated TG/HDL-C ratio in T2DM patients
OR95% CIP-value
CKD4.212.13-8.33<0.001
Elevated HbA1c2.471.23-4.950.011
Glucose levels1.010.98-1.010.182
WC0.990.97-1.030.949
SystBP0.990.97-1.020.514
DiastBP0.990.97-1.030.957
Age1.010.98-1.040.588
Sex0.760.39-1.470.418

Table 2: Association of elevated TG/HDL-C ratio with CKD and HbA1c after adjusting for their covariates in these T2DM patients.

Discussion

Our present study demonstrated that elevated TG/HDL ratio group had lower HDL-C, eGFR levels and higher Glu, HbA1c, TC, TG and LDL-C. We also demonstrated the association between elevated TG/HDL-C ratio with CKD and elevated HbA1c after adjusting for their covariates. Dyslipidemia in T2DM patients is common, and is the major risk factor in cardiovascular disease (CVD). It also has a role in the pathogenisis and progression of diabetic nephropathy (DN). Many research studies demonstrated that the large amount of the excessive lipids and lipoproteins worsens diabetes-related microvascular diseases with complications including glomerular injury, tubulointerstitial fibrosis and accelerated progression of DN [22, 23]. Patients with T2DM and CKD also have higher VLDL, LDL, IDL and TG but lower HDL levels than levels in patients without diabetes [3, 23, 24]. The LDL particles in T2DM patients tend to be smaller, denser and more atherogenic [19, 25]. TG/HDL-C ratio was used as the estimation of insulin resistance and the indicator of LDL particle size in T2DM patients [17, 19]. Insulin resistance and the disorder of insulin action in lipid and lipoprotein metabolism are the major mechanisms changed in lipid and lipoprotein profile in T2DM and DN patients. The enhancing of lipolysis results in increased free fatty acids and VLDL synthesis concomitant with the defection in LPL activity leading to prolong the life span of chylomicron, VLDL and TG elevation in circulation, increased TG transfer with cholesterol esters in lipoproteins resulting in triglyceride-rich LDL, HDL and reduction of LPL to hepatic lipase ratio to cause the acceleration of HDL breakdown in circulation [26]. Further, all the lipoprotein abnormalities and triglyceride-rich lipoproteins (TGRLs) are involved in the increasing albuminuria, declining renal function and development of CKD [26, 27, 28], concomitant with increased total cholesterol and LDL levels which are associated with Tangvarasittichai S, et al. Increased Triglycerides and High Density Lipoprotein Ratio Associated with Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus. Diabetes Obes Int J 2017, 2(4): 000166.

Copyright© Tangvarasittichai S, et al.

Management of hyperglycemia has been focused on the lowering of glycosylated hemoglobin (HbA1c) levels, as the recommendation of the International Diabetes Federation and the American College of Endocrinology the HbA1c values is <48 mmol/mol (<6.5%) in T2DM patients. Large outcome trials study suggested that the >48 mmol/mol (>6.5%) HbA1c was the predictor of the diabetes complications [34]. T2DM patients in the present study demonstrated the HbA1c levels >48 mmol/mol (>6.5%), perhaps indicating prevalence of postprandial hyperglycemia. Many research studies demonstrated that diet management and exercise strategies can improve postprandial hyperglycemia and hyperlipidemia, inflammation, and endothelial function [35, 36]. Pharmacologic management for postprandial dysmetabolism with statins (simvastatin is the HMG CoA reductase inhibitors drug) reduced LDL-C, TG and increased HDL-C and also exerts antioxidant activity [37, 38]. This drug has demonstrated the inflammatory reduction. Ceriello, et al. demonstrated that atorvastatin can reduce the adverse effect of postprandial dysmetabolism in T2DM patients [38]. Conventional diabetic drugs such as sulfonylurea’s and insulin can predominantly lower fasting glucose while metformin is effective in reducing both fasting and postprandial hyperglycemia. Acarbose, exenatide, incretin enhancers, and fast-acting insulin are the most effective drugs for lowering postprandial glucose [39]. Thus, all of these intervention regimens in these T2DM patients may need to revisit (or readjust or reconsider in treatment dose).

Conclusion

The evidence demonstrated that increased TG/HDL-C ratio associated with CKD, along with elevated HbA1c, may increase the progression of renal disease in these T2DM patients. The reduction of HDL-C levels may play the major role in the development of CKD and the progression of renal function and structural damage.

Acknowledgement

We sincerely thank Ladyao Hospital, Nakornsawan Province for financial support and all co-workers of Clinical Laboratory for their technical assistance. We sincerely thank Asst. Prof. Dr. Ronald A. Markwardt, Burapha University, for his reading and correcting of the manuscript.

Conflict of Interest

The authors declare that they have no competing interests.

References

  1. Garg A, Grundy SM (1990) Management of dyslipidemia in NIDDM. Diabetes Care 13(2): 153- 169.
  2. Tangvarasittichai S (2015) Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 6(3): 456-480.
  3. Tangvarasittichai S (2017) Atherogenic dyslipidemia: An important risk factor for cardiovascular disease in metabolic syndrome and type 2 diabetes mellitus patients. Diabetes Obes Int J 2(1): 1-19.
  4. Laws A, Reaven GM (1992) Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Intern Med 231(1): 25-30.
  5. James MT, Hemmelgarn BR, Tonelli M (2010) Early recognition and prevention of chronic kidney disease. Lancet 375(9722): 1296-309.
  6. Jha JC, Jandeleit-Dahm KA, Cooper ME (2014) New insights into the use of biomarkers of diabetic nephropathy. Adv Chronic Kidney Dis 21(3): 318- 326.
  7. Mc Brien KA, Manns BJ, Chui B, Klarenbach SW, Rabi D, et al. (2013) Health care costs in people with diabetes and their association with glycemic control and kidney function. Diabetes Care 36(5): 1172-1180.
  8. Nag S, Bilous R, Kelly W, Jones S, Roper N, Connolly V (2007) All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years’ data from the South Tees Diabetes Mortality study. Diabet Med 24(1): 10-17.
  9. Cea Soriano L, Johansson S, Stefansson B, Rodríguez LA (2015) Cardiovascular events and all-cause mortality in a cohort of 57,946 patients with type 2 diabetes: associations with renal function and cardiovascular risk factors. Cardiovasc Diabetol 14: 38.
  10. Palsson R, Patel UD (2014) Cardiovascular complications of diabetic kidney disease. Adv Chronic Kidney Dis 21(3): 273-280.
  11. National Kidney Foundation (2002) K/DOQI Clinical Practice Guideline for Chronic Kidney Disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2S1): S1-266.
  12. Afkarian M, Sachs MC, Kestenbaum B, Hirsch IB, Tuttle KR, et al. (2013) Kidney disease and increased mortality risk in type 2 diabetes. J Am SocNephrol 24(2): 302-308.
  13. Ritz E, Wanner C (2006) Lipid changes and statins in chronic renal insufficiency. J Am SocNephrol 17(12 S3): S226-S230.
  14. Vaziri ND (2006) Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. Am J Physiol Renal Physio 290(2): F262-272.
  15. Parikh NI, Hwang SJ, Larson MG, Meigs JB, Levy D, et al. (2006) Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control. Arch Intern Med 166(17): 1884-1891.
  16. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE (1997) Fasting triglycerides, high- density lipoprotein, and risk of myocardial infarction. Circulation 96(8): 2520-2525.
  17. Tangvarasittichai S, Poonsub P, Tangvarasittichai O (2010) Association of serum lipoprotein ratios with insulin resistance in type 2 diabetes mellitus. Indian J Med Res131: 641-648.
  18. Boizel R, Benhamou PY, Lardy B, Laporte F, Foulon T, et al. (2000) Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels. Diabetes Care 23(11): 1679- 1685.
  19. Bhalodkar NC, Blum S, Enas EA (2006) Accuracy of the ratio of triglycerides to high density lipoprotein cholesterol for predicting low-density lipoprotein cholesterol particle sizes, phenotype B, and particle concentrations among Asian Indians. Am J Cardiol 97(7): 1007-1009.
  20. Maruyama C, Imamura K, Teramoto T (2003) Assessment of LDL particle size by triglyceride/HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia. J Atheroscler Thromb 10(3): 186- 191.
  21. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1): 31-41.
  22. Yoshino G, Hirano T, Kazumi T (2002) Atherogenic lipoproteins and diabetes mellitus. J Diabetes Complicat 16(1): 29-34.
  23. Jenkin AJ, Lyon TJ, Zheng D, Otvos JD, Lackland DT, et al. (2003) Lipoproteins in the DCCT/EDIC cohort: Associations with diabetic nephropathy. Kidney Int 64(3): 817-828.
  24. Trovati M, Cavalot F (2004) Optimization of hypolipidemic and antiplatelet treatment in the diabetic patient with renal diseases. J Am Soc Nephrol 15: S12-S20.
  25. Moorhead JF, Chan MK, El-Nahas M, Varghese Z (1982) Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 2(1309): 1309-1311.
  26. Rutledge JC, Ng KF, Aung HH, Wilson DW (2010) Role of triglyceride-rich lipoprotein in diabetic nephropathy. Nat Rev Nephrol 6(6): 361-370.
  27. Ravid M, Brosh D, Ravid-Safran D, Levy Z, Rachmani R (1998) Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia. Arch Intern Med 158(9): 998-1004.
  28. Nelson CL, Karschimkus CS, Dragicevic G, Packham DK, Wilson AM, et al. (2005) Systemic and vascular inflammation is elevated in early IgA and type 1 diabetic nephropathies and relates to vascular disease risk factors and renal function. Nephrol Dial Transplant 20(11): 2420-2426.
  29. Speer T, Rohrer L, Blyszczuk P, Shroff R, Kuschnerus K, et al. (2013) Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2. Immunity 38(4): 754-768.
  30. American Diabetes Association (2001) Post- prandial Glucose-Consensus Statement. Diabetes Care 24(4): 775-778.
  31. Ceriello A, Genovese S (2016) Atherogenicity of postprandial hyperglycemia and lipotoxicity. Rev Endocr Metab Disord 17(1): 111-116.
  32. Klop B, Proctor S, Mamo J, Botham K, Cabezas M (2011) Understanding postprandial inflammation and its relationship to lifestyle behavior and metabolic diseases. Int J Vasc Med 2012: 1-11.
  33. Tangvarasittichai S, Deebukkhum S, Tangvarasittichai O (2016) Progression of Increased Oxidative Stress and Inflammation in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus. Inter J Pharmac Clinl Res 8(6): 596-603.
  34. American Diabetes Association (2015) Standards of medical care in diabetes -2015. Diabetes Care 38(1): S1-93.
  35. O’Keefe JH, Gheewala NM, O’Keefe JO (2008) Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol 51(3): 249-255.
  36. Tangvarasittichai S, Lertsinthai P, Taechasubamorn P, Veerapun O, Tangvarasittichai O (2009) Effect of moderate-intensity exercise training on body weight, serum uric acid, serum hs-CRP, and insulin sensitivity in type 2 diabetic patients. Siriraj Med J 61(6): 310-313.
  37. Ceriello A, Assaloni R, Da Ros R, Maier A,Ludovica P, et al. (2005) Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 111(19): 2518-2524.
  38. Ceriello A, Motz E (2004) Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? Arterioscler Thromb Vasc Biol 24(5): 816-823.
  39. Lund SS, Tarnow L, Frandsen M, Smidt UM, Pedersen O, et al. (2008) Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes. Eur J Endocrinol 158(1): 35-46.
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@article{sengsuk2017,
  title   = {Increased Triglycerides and High Density Lipoprotein Ratio Associated with Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus},
  author  = {Sengsuk J1 Tangvarasittichai O2 and Tangvarasittichai S2},
  journal = {Diabetes & Obesity International Journal},
  year    = {2017},
  volume  = {2},
  number  = {4},
  doi     = {10.23880/doij-16000166}
}
Sengsuk J1 Tangvarasittichai O2 and Tangvarasittichai S2 (2017). Increased Triglycerides and High Density Lipoprotein Ratio Associated with Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus. Diabetes & Obesity International Journal, 2(4). https://doi.org/10.23880/doij-16000166
TY  - JOUR
TI  - Increased Triglycerides and High Density Lipoprotein Ratio Associated with Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus
AU  - Sengsuk J1 Tangvarasittichai O2 and Tangvarasittichai S2
JO  - Diabetes & Obesity International Journal
PY  - 2017
VL  - 2
IS  - 4
DO  - 10.23880/doij-16000166
ER  -