Relationship between Thyroid Function and Kidney Function in Patients with Type 2 Diabetes

Zhang, Ying; Wang, Yang; Tao, Xiao Jun; Li, Qian; Li, Feng Fei; Lee, Kok Onn; Li, Dong Mei; Ma, Jian Hua

doi:https://doi.org/10.1155/2018/1871530

International Journal of Endocrinology

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Abstract Introduction Materials and Methods Results Discussion Conclusion Data Availability Additional Points Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2018 | Article ID 1871530 | https://doi.org/10.1155/2018/1871530

Relationship between Thyroid Function and Kidney Function in Patients with Type 2 Diabetes

Ying Zhang,¹Yang Wang,²Xiao Jun Tao,¹Qian Li,¹Feng Fei Li,¹Kok Onn Lee,³Dong Mei Li,¹and Jian Hua Ma¹

Academic Editor: Jack Wall

Received18 Jun 2018

Accepted24 Sept 2018

Published14 Nov 2018

Abstract

Purpose. To determine if the TSH is related to estimated glomerular filtration rate (eGFR) in T2D patients without overt thyroid dysfunction. Methods. A cohort study of 5936 T2D patients was assessed for thyroid and kidney functions, in whom 248 with subclinical hyperthyroidism and 362 with subclinical hypothyroidism. Serum creatinine and 24-hour urine albumin excretion (UAE) were collected. Chronic kidney disease (CKD) was defined as eGFR < 60 ml/min/1.73 m². Results. Compared with euthyroid subjects, the patients with subclinical hypothyroidism had lower eGFR (82.7 ± 22.4 vs. 90.5 ± 22.4 ml/min/1.73 m², ), higher UAE (114 ± 278 vs. 88 ± 229 mg/24 h, ), and high incidence of CKD (16.0% vs. 10.1%, ). The participants with a TSH level between 0.55 and 3.0 μIU/ml had a higher eGFR (91.4 ± 22.2 ml/min/1.73 m²) and a lower prevalence of CKD (9.5%) than those with higher TSH (3.01–4.78 μIU/ml, 85.6 ± 22.7 ml/min/1.73 m², and 13.1%, ). Linear logistic regression analysis showed that the eGFR was significantly negatively associated with TSH (OR: 0.519, 95% CI: 0.291–0.927, ), after adjustment of confounders. Conclusion. High TSH was independently associated with decreased eGFR in type 2 diabetes patients without overt thyroid dysfunction. Our findings indicate that doctors who treat T2D patients should routinely measure the thyroid function.

1. Introduction

Many patients with T2D develop chronic kidney disease, which is defined based on glomerular filtration rate < 60 ml/min/1.73 m² and/or the presence of albuminuria, as defined in the recommendations of the 2012 KDIGO practice guideline [1]. The kidney functions in patients with T2D were influence by many situations and medicine, such as hypertension [2], lipid profiles [3], glycemic variability [4], and the renin-angiotensin-aldosterone system blockade [5]. The development of significant CKD is associated with an increased risk of adverse cardiovascular outcomes and death in patients with T2D [6, 7].

Overt thyroid disease is relatively uncommon in T2D, and only a few studies investigated their relationship with kidney function in T2D. Some studies have shown that overt and subclinical hypothyroidisms were associated with reduced eGFR and increased risk of CKD [8–11] and that unresolved subclinical hypothyroidism was independently associated with the rate of renal function decline [12].

Despite overt thyroid disease being uncommon in type 2 diabetic patients, there is an increase in subclinical hypothyroidism in these patients when compared with healthy population [13], but it is not known if the change in eGFR and CKD in these patients with T2D is related to thyroid function, especially in patients within the normal range of TSH. We therefore assessed the association of thyroid function with eGFR, 24-hour urine albumin excretion (UAE), and CKD in a large cross-sectional population study of type 2 diabetic participants without overt thyroid dysfunction.

2. Materials and Methods

2.1. Study Population

A consecutive series of 6172 Chinese participants with type 2 diabetes who visited Nanjing First Hospital, Nanjing Medical University between January 2012 and December 2017 were enrolled in this retrospective observational study.

The study was approved by the Medical Ethics Committee of Nanjing First Hospital Affiliated to Nanjing Medical University, and written informed consent was obtained from all participants.

The patients who met the following criteria were excluded: patients with a previous known history of thyroid dysfunction (), thyroidectomy (), pituitary disease (), autoimmune renal diseases, renal artery stenosis, or end-stage renal disease under maintenance dialysis kidney disease (). We further excluded subjects who were younger than 18 years of age, women who were pregnant, subjects with urinary tract infection, or subjects who were receiving concurrent treatment with drugs that could affect the thyroid function (lithium, amiodarone, or iodine).

2.2. Clinical Measurements

Demographic and clinical data including comorbidities, the use of antidiabetic medications, and the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) were obtained from the medical records of these participants. Body mass index (BMI) was calculated based on body weight (in kilograms) divided by body height in meters squared (kg/m²).

Serum creatinine, fasting blood glucose (FBG), lipid profiles (total cholesterol, triglycerides, and high- and low-density lipoproteins) were analyzed by enzymatic assays (Olympus AU5400 autoanalyzer; Beckman Coulter, Japan). Glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography (Bio-Rad, USA). UAE was determined by chemiluminescence immunoassay (Siemens, Germany).

2.3. Thyroid Function

Thyroid function was assessed by measurement of TSH (reference range: 0.55–4.78 μIU/ml, chemiluminescence immunoassay, Siemens, Germany) and FT4 (reference range: 11.5–22.7 pmol/l, chemiluminescence immunoassay, Siemens, Germany). Subclinical hyperthyroidism was defined as a TSH level < 0.55 mIU/l with a FT4 level within normal range. Subclinical hypothyroidism was defined as a TSH level > 4.78 mIU/l with a FT4 level within normal range. Euthyroid state was defined as a TSH level from 0.55 mIU/l to 4.78 mIU/l with a FT4 level within normal range.

2.4. UAE and CKD

Abnormal UAE was defined according to the criteria of the American Diabetes Association (UAE ≥ 30 mg/24 h). The definition of microalbuminuria was UAE 30–299 mg/24 h, and macroalbuminuria was UAE ≥ 300 mg/24 h. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was harnessed to calculate the estimated glomerular filtration rate (eGFR), which was as follows: , where = 144 (female) or 141 (male), = 0.7 (female) or 0.9 (male), and = −0.329 (female with serum creatinine ≤ 0.7 mg/dl), −0.419 (male with serum creatinine ≤ 0.7 mg/dl), and− 1.209 (male and female with serum creatinine > 0.7 mg/dl). The presence of chronic kidney disease (CKD) was defined as having an eGFR < 60 ml/min/1.73 m².

2.5. Statistical Analysis

SPSS version 23.0 for MAC was used in all analyses. The duration of diabetes was presented as mean ± standard error; the other descriptive statistics were presented as mean ± standard deviation and numbers (percentages) for categorical variables. The significance of differences between any two groups was assessed by -test; one-way analysis of variance (ANOVA) was utilized for comparing three groups or more, and -test was chosen to compare categorical variables. If significant differences were found using one-way ANOVA, a post hoc least significant difference test was used to define the effective factors. We used the linear logistic regression analysis to examine the association between eGFR and TSH, and binary logistic regression analysis was used to investigate the risk factors for CKD. We also used Pearson’s test to analyze the correlation between eGFR levels and the clinical characteristics of the participants. A value < 0.05 was considered statistically significant.

3. Results

3.1. Participant Characteristics

Thyroid function testing found 29 patients with overt hyperthyroidism and 21 overt hypothyroidism; they were excluded from the analysis. A final total of 5936 patients with T2D were included into this study (Table 1 and Figure 1). These patients had a mean diabetic duration of 8.2 ± 6.8 years, with a mean HbA1c level of 9.2 ± 2.6%. Among these T2D patients, 1956 received insulin (either alone or in combination with sulfonylurea, metformin, or acarbose) and 1926 patients received sulfonylurea (either alone or in combination with metformin or acarbose). Metformin, which has been reported to lower TSH [14, 15], was used in 1127 subjects. Hypertension was present in 3547 (59.8%) subjects, and 1614 (45.5%) subjects were on ACEI or ARB.

3.2. UAE and CKD

Among the 5936 patients, 629 (10.6%) had evidence of CKD with an eGFR of <60 ml/min/1.73 m², while 2087 (35.2%) had significant UAE, 1610 (27.1%) had microalbuminuria, and 477 (8.0%) had macroalbuminuria.

The UAE levels increased with the CKD stages (all , Figure 2). The prevalence of DN, microalbuminuria, and macroalbuminuria also increased with the CKD stages (all for trend < 0.01). Pearson correlation analysis showed that UAE was negatively correlated with eGFR ( = −0.0273, ).

3.3. Thyroid Function

Among the 5936 patients, 5326 (89.7%) were euthyroid, 248 (4.2%) had subclinical hyperthyroidism, and 362 (6.1%) had subclinical hypothyroidism (Figure 1). Compared with euthyroid subjects, the patients with subclinical hypothyroidism were found more frequent female with the usage of metformin. The subclinical hypothyroid patients were also older, had higher BMI, longer duration of diabetes, higher HbA1c, and higher blood pressure. They also had lower eGFR, higher UAE, and more CKD (eGFR < 60 ml/1.73 m²). By contrast, the 248 patients with subclinical hyperthyroidism subjects did not have any of these significant changes (Table 1). No significant differences were found in the prevalence of DN, microalbuminuria, or macroalbuminuria among the three groups.

3.4. Renal Function and CKD Related to TSH Levels

In 5326 participants with normal TSH, 4476 participants are with a TSH level from 0.55 to 3.00 μIU/ml and 850 participants are with a TSH level between 3.01 and 4.78 μIU/ml. Among 4476 with a TSH level from 0.55 to 3.00 μIU/ml, 427 (9.5%) participants had CKD, lower than that in participants with a TSH level between 3.01 and 4.78 μIU/ml (111 of 850, 13.1%, ) and participants with subclinical hyperthyroidism (16.0%, , Figure 3).

The participants with a lower TSH level between 0.55 and 3.00 had a significant higher eGFR (91.4 ± 22.2 ml/min/1.73 m²) than those with a higher TSH level (TSH 3.01–4.78, 85.6 ± 22.7 ml/min/1.73 m², ), those with subclinical hypothyroidism (82.8 ± 22.4 ml/min/1.73 m², ), and those with subclinical hyperthyroidism (88.5 ± 24.6 ml/min/1.73 m², , Figure 4). The levels of UAE and the prevalence of DN were not significantly different among the four groups (TSH < 0.55 μIU/ml, 0.55 to 3.00 μIU/ml, 3.01 and 4.78 μIU/ml, and >4.78 μIU/ml).

When all the 5936 subjects included in the analysis were further divided into 4 quartiles according to the TSH levels (<1.168, 1.168–1.797, 1.798–2.694, >2.694 μIU/ml), the TSH levels were negatively correlated with the eGFR levels. The participants in the third and the forth quartiles of the TSH group had significant lower eGFR than other groups (92.1 ± 22.9 first quartile, 92.4 ± 21.6 second, 89.3 ± 22.5 third, and 86.0 ± 22.7 forth, all ). There is no relationship in UAE levels associated with TSH levels.

3.5. Correlation between eGFR and TSH

Pearson correlation analysis indicated that there were negative relationships between eGFR and TSH ( = −0.086, ), eGFR and age ( = −0.580, ), eGFR and the duration of diabetes ( = −0.270, ), and eGFR and hypertension ( = −0.195, ). The above correlations were similar in males or females, regardless of hypertension. By contrast, no correlation was found between eGFR and FT₄.

Linear regression analysis showed that eGFR was significantly negatively associated with TSH (OR: 0.416, 95% CI: 0.321–0.539, ). The association remained significant after adjustment of age and gender (OR: 0.403, 95% CI: 0.276–0.589, ) and further adjustment for diabetes duration, HbA1c, TC, TG, and HDL (OR: 0.519, 95% CI: 0.291–0.927, ). Binary logistic regression showed that TSH is an important risk factor for CKD (OR: 1.036, 95% CI: 1.005–1.068, ), but the statistical significance disappeared after adjustment for gender and age.

4. Discussion

In this cross-sectional population study, high TSH levels were associated with reduced eGFR in type 2 diabetes patients without overt thyroid dysfunction. The association was independent of age, gender, diabetes duration, usage of metformin, HbA1c, TC, TG, and HDL levels.

Results from previous studies suggested that overt and subclinical hypothyroidisms were associated with reduced GFR and higher prevalence of CKD [8–11]. Our results support these observations and, in addition, suggest that low thyroid function within the clinically normal range is associated with reduced GFR and high prevalence of CKD.

Thyroid hormones influence kidney function by direct renal effects as well as systemic hemodynamic [16], metabolic, and cardiovascular effects [17]. Previous studies showed that overt and subclinical hypothyroidisms were associated with reduced eGFR and increased risk of CKD and unresolved subclinical hypothyroidism were independently associated with the rate of renal function decline [12], and thyroid hormone supplement attenuated the alterations [18–20].

It has been suggested that GFR may increase following thyroid hormone supplement in hypothyroidism [18–22], while GFR may be reduced after treatment for hyperthyroidism [21] or after withdrawal of T4 treatment [23]. These findings suggest that low thyroid function may cause reduction in GFR.

Hypothyroidism may decrease ventricular diastolic function [24] and cardiac output, increase peripheral vascular resistance, and result in reduction in renal blood flow [25]. These effects may be ameliorated by thyroid hormone treatment [22, 24]. Subclinical hypothyroidism is also associated with endothelial dysfunction [26] and impaired microvascular function [27]. These findings suggest that low thyroid function might lead to reduced GFR.

On the other hand, it has also been suggested that decreased renal function may influence the thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported [28]. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion and clearance of pituitary thyrotropin (TSH) is impaired in uremia [28].

Our large study showed that the prevalence of CKD increased with elevated TSH levels, 9.5% (427 out of 4476) in participants with TSH from 0.55 to 3.00 μIU/ml, 13.1% (111 out of 850) in participants with TSH from 3.01 to 4.78 μIU/ml, and 16.0% (58 out of 362) in participants with subclinical hypothyroidism.

Furthermore, a significant inverse association between eGFR and TSH levels was observed throughout whole TSH ranges, which was in accordance with the previous studies [8]. Many situations and medication have effects on kidney functions, such as hypertension [2], lipid profiles [3], glycemic variability [4], and the renin-angiotensin-aldosterone system blockade [5]. Linear regression analysis did not show the association between eGFR and the presence of hypertension or the usage of ACEI/ARB. It might because of the high prevalence of hypertension and the usage of ACEI/ARB in our studied subjects. This relationship was independent of age, gender, duration of diabetes, HbA1c, TC, TG, and HDL levels. Thyroid function, also within the clinically normal range [16], has been positively associated with effective renal plasma flow [22, 28], supporting our results.

Controversies exist as to the reference range for “normal” TSH. Some suggested that TSH upper limit should be decreased from 4.5–5.0 mIU/ml to 2.5–3.0 mIU/ml based on a higher risk of the progression to organ damage [29]. Our evidence supports this view that the prevalence of CKD in participants with TSH from 3.01 to 4.78 μIU/ml was higher than that in participants with TSH from 0.55 to 3.00 μIU/ml and similar to that in participants with subclinical hypothyroidism (TSH > 4.78 μIU/ml). The optimal range of TSH needs further investigation.

Albuminuria is associated with the progression of diabetic kidney disease [30], a faster decline in GFR [31], and an important risk factor of cardiovascular disease [32]. The definition of DN, microalbuminuria, or macroalbuminuria may be inaccurate. These may contribute to the insignificant difference among different TSH groups.

There are some limitations in the present study. First, this is a cross-sectional investigation that demonstrated the association between TSH and CKD, which do not provide information on a causation relationship. Second, we used creatinine-based estimates of GFR. Creatinine production was reduced and tubular secretion was increased in overt hyperthyroidism [33, 34], and therefore, GFR might be overestimated. However, it is not known if creatinine kinetics is influenced by subclinical thyroid dysfunction or thyroid function within the normal range. Smaller studies that have used inulin or ⁵¹Cr-EDTA clearance to estimate GFR [22, 35, 36] have found that hypothyroidism may be associated with reduced GFR, and these methods do not depend on creatinine levels to estimate GFR. The accuracy of CKD-EPI equation to estimate GFR has already confirmed and validated in the previous studies [37, 38]. Third, the reference range for “normal” TSH was under debate. The relationship between TSH and CKD needs more qualitative analysis. A linear association between TSH and eGFR is supplementary to this limitation. Fourth, the glycemic variability was not measured in the present study. Increasing evidence showed that increased glycemic variability positively associated with chronic complications in diabetic patients [39]. Patients with higher HbA1c had larger glycemic variations [40]. The levels of HbA1c in the present study were moderately higher. The patients under sulphonylureas or insulin therapy, thought to be with worse β cell function and longer duration, had larger glycemic variation. Similar portions of patients under sulphonylureas or insulin therapy among three groups might imply that the influence of glycemic variations is limited. Therefore, further large prospective studies were needed to confirm the detrimental effect of high TSH on the kidney.

5. Conclusion

High TSH was independently associated with the decreased eGFR in patients with T2D without overt thyroid dysfunction. Our findings indicate that doctors who treat T2D patients should routinely measure the thyroid function.

Data Availability

The datasets generated and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Additional Points

Highlights. In patients with T2D, subclinical hypothyroidism was associated with lower eGFR, a higher incidence of CKD, and higher UAE. eGFR was significantly negatively associated with TSH.

Conflicts of Interest

All authors have no conflicts of interest.

Acknowledgments

This work was funded by grant from the National Natural Science Foundation of China (81100576 and 8110512).

References

L. A. Inker, B. C. Astor, C. H. Fox et al., “KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD,” American Journal of Kidney Diseases, vol. 63, no. 5, pp. 713–735, 2014.
View at: Publisher Site | Google Scholar
M. Teliti, G. Cogni, L. Sacchi et al., “Risk factors for the development of micro-vascular complications of type 2 diabetes in a single-centre cohort of patients,” Diabetes & Vascular Disease Research, vol. 15, no. 5, pp. 424–432, 2018.
View at: Publisher Site | Google Scholar
G. T. Russo, S. de Cosmo, F. Viazzi et al., “Plasma triglycerides and HDL-C levels predict the development of diabetic kidney disease in subjects with type 2 diabetes: the AMD annals initiative,” Diabetes Care, vol. 39, no. 12, pp. 2278–2287, 2016.
View at: Publisher Site | Google Scholar
H. S. Jung, “Clinical implications of glucose variability: chronic complications of diabetes,” Endocrinology and Metabolism, vol. 30, no. 2, pp. 167–174, 2015.
View at: Publisher Site | Google Scholar
S. S. Roscioni, H. J. L. Heerspink, and D. de Zeeuw, “The effect of RAAS blockade on the progression of diabetic nephropathy,” Nature Reviews Nephrology, vol. 10, no. 2, pp. 77–87, 2014.
View at: Publisher Site | Google Scholar
R. N. Foley, A. M. Murray, S. Li et al., “Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999,” Journal of the American Society of Nephrology, vol. 16, no. 2, pp. 489–495, 2005.
View at: Publisher Site | Google Scholar
S. I. Hallan, K. Matsushita, Y. Sang et al., “Age and association of kidney measures with mortality and end-stage renal disease,” Journal of the American Medical Association, vol. 308, no. 22, pp. 2349–2360, 2012.
View at: Publisher Site | Google Scholar
B. O. Asvold, T. Bjoro, and L. J. Vatten, “Association of thyroid function with estimated glomerular filtration rate in a population-based study: the HUNT study,” European Journal of Endocrinology, vol. 164, no. 1, pp. 101–105, 2011.
View at: Publisher Site | Google Scholar
B. Gopinath, D. C. Harris, J. R. Wall, A. Kifley, and P. Mitchell, “Relationship between thyroid dysfunction and chronic kidney disease in community-dwelling older adults,” Maturitas, vol. 75, no. 2, pp. 159–164, 2013.
View at: Publisher Site | Google Scholar
C. M. Rhee, K. Kalantar-Zadeh, E. Streja et al., “The relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease,” Nephrology, Dialysis, Transplantation, vol. 30, no. 2, pp. 282–287, 2015.
View at: Publisher Site | Google Scholar
Q. Qi, Q. M. Zhang, C. J. Li et al., “Association of thyroid-stimulating hormone levels with microvascular complications in type 2 diabetes patients,” Medical Science Monitor, vol. 23, pp. 2715–2720, 2017.
View at: Publisher Site | Google Scholar
E. O. Kim, I. S. Lee, Y. A. Choi et al., “Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease,” International Journal of Medical Sciences, vol. 11, no. 1, pp. 52–59, 2014.
View at: Publisher Site | Google Scholar
C. Han, X. He, X. Xia et al., “Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis,” PLoS One, vol. 10, no. 8, article e0135233, 2015.
View at: Publisher Site | Google Scholar
C. Cappelli, M. Rotondi, I. Pirola et al., “TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients,” Diabetes Care, vol. 32, no. 9, pp. 1589-1590, 2009.
View at: Publisher Site | Google Scholar
R. Lupoli, A. di Minno, A. Tortora, P. Ambrosino, G. Arianna Lupoli, and M. N. D. di Minno, “Effects of treatment with metformin on TSH levels: a meta-analysis of literature studies,” The Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 1, pp. E143–E148, 2014.
View at: Publisher Site | Google Scholar
O. Gumieniak, T. S. Perlstein, P. N. Hopkins et al., “Thyroid function and blood pressure homeostasis in euthyroid subjects,” The Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 7, pp. 3455–3461, 2004.
View at: Publisher Site | Google Scholar
P. Iglesias, M. A. Bajo, R. Selgas, and J. J. Diez, “Thyroid dysfunction and kidney disease: an update,” Reviews in Endocrine & Metabolic Disorders, vol. 18, no. 1, pp. 131–144, 2017.
View at: Publisher Site | Google Scholar
M. Adrees, J. Gibney, N. El-Saeity, and G. Boran, “Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism,” Clinical Endocrinology, vol. 71, no. 2, pp. 298–303, 2009.
View at: Publisher Site | Google Scholar
Y. Lu, H. Guo, D. Liu, and Z. Zhao, “Preservation of renal function by thyroid hormone replacement in elderly persons with subclinical hypothyroidism,” Archives of Medical Science, vol. 12, no. 4, pp. 772–777, 2016.
View at: Publisher Site | Google Scholar
D. H. Shin, M. J. Lee, H. S. Lee et al., “Thyroid hormone replacement therapy attenuates the decline of renal function in chronic kidney disease patients with subclinical hypothyroidism,” Thyroid, vol. 23, no. 6, pp. 654–661, 2013.
View at: Publisher Site | Google Scholar
J. G. den Hollander, R. W. Wulkan, M. J. Mantel, and A. Berghout, “Correlation between severity of thyroid dysfunction and renal function,” Clinical Endocrinology, vol. 62, no. 4, pp. 423–427, 2005.
View at: Publisher Site | Google Scholar
A. Elgadi, P. Verbovszki, C. Marcus, and U. B. Berg, “Long-term effects of primary hypothyroidism on renal function in children,” The Journal of Pediatrics, vol. 152, no. 6, pp. 860–864, 2008.
View at: Publisher Site | Google Scholar
S. H. Kreisman and J. V. Hennessey, “Consistent reversible elevations of serum creatinine levels in severe hypothyroidism,” Archives of Internal Medicine, vol. 159, no. 1, pp. 79–82, 1999.
View at: Publisher Site | Google Scholar
M. Yazici, S. Gorgulu, Y. Sertbas et al., “Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function,” International Journal of Cardiology, vol. 95, no. 2-3, pp. 135–143, 2004.
View at: Publisher Site | Google Scholar
I. Klein and K. Ojamaa, “Thyroid hormone and the cardiovascular system,” The New England Journal of Medicine, vol. 344, no. 7, pp. 501–509, 2001.
View at: Publisher Site | Google Scholar
A. R. Cappola and P. W. Ladenson, “Hypothyroidism and atherosclerosis,” The Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 6, pp. 2438–2444, 2003.
View at: Publisher Site | Google Scholar
S. Baycan, D. Erdogan, M. Caliskan et al., “Coronary flow reserve is impaired in subclinical hypothyroidism,” Clinical Cardiology, vol. 30, no. 11, pp. 562–566, 2007.
View at: Publisher Site | Google Scholar
P. Iglesias and J. J. Diez, “Thyroid dysfunction and kidney disease,” European Journal of Endocrinology, vol. 160, no. 4, pp. 503–515, 2009.
View at: Publisher Site | Google Scholar
H. Volzke, D. M. Robinson, T. Spielhagen et al., “Are serum thyrotropin levels within the reference range associated with endothelial function?” European Heart Journal, vol. 30, no. 2, pp. 217–224, 2009.
View at: Publisher Site | Google Scholar
W. F. Keane, B. M. Brenner, D. de Zeeuw et al., “The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study,” Kidney International, vol. 63, no. 4, pp. 1499–1507, 2003.
View at: Publisher Site | Google Scholar
T. Babazono, I. Nyumura, K. Toya et al., “Higher levels of urinary albumin excretion within the normal range predict faster decline in glomerular filtration rate in diabetic patients,” Diabetes Care, vol. 32, no. 8, pp. 1518–1520, 2009.
View at: Publisher Site | Google Scholar
K. P. Klausen, H. Scharling, G. Jensen, and J. S. Jensen, “New definition of microalbuminuria in hypertensive subjects: association with incident coronary heart disease and death,” Hypertension, vol. 46, no. 1, pp. 33–37, 2005.
View at: Publisher Site | Google Scholar
J. Verhelst, J. Berwaerts, B. Marescau et al., “Serum creatine, creatinine, and other guanidino compounds in patients with thyroid dysfunction,” Metabolism, vol. 46, no. 9, pp. 1063–1067, 1997.
View at: Publisher Site | Google Scholar
T. Shirota, T. Shinoda, T. Yamada, and T. Aizawa, “Alteration of renal function in hyperthyroidism: increased tubular secretion of creatinine and decreased distal tubule delivery of chloride,” Metabolism, vol. 41, no. 4, pp. 402–405, 1992.
View at: Publisher Site | Google Scholar
G. Karanikas, M. Schütz, M. Szabo et al., “Isotopic renal function studies in severe hypothyroidism and after thyroid hormone replacement therapy,” American Journal of Nephrology, vol. 24, no. 1, pp. 41–45, 2004.
View at: Publisher Site | Google Scholar
C. Villabona, M. Sahun, N. Gómez et al., “Blood volumes and renal function in overt and subclinical primary hypothyroidism,” The American Journal of the Medical Sciences, vol. 318, no. 4, pp. 277–280, 1999.
View at: Publisher Site | Google Scholar
L. A. Stevens, C. H. Schmid, Y. L. Zhang et al., “Development and validation of GFR-estimating equations using diabetes, transplant and weight,” Nephrology, Dialysis, Transplantation, vol. 25, no. 2, pp. 449–457, 2010.
View at: Publisher Site | Google Scholar
L. A. Stevens, C. H. Schmid, T. Greene et al., “Comparative performance of the CKD epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD) study equations for estimating GFR levels above 60 mL/min/1.73 m²,” American Journal of Kidney Diseases, vol. 56, no. 3, pp. 486–495, 2010.
View at: Publisher Site | Google Scholar
C. Gorst, C. S. Kwok, S. Aslam et al., “Long-term glycemic variability and risk of adverse outcomes: a systematic review and meta-analysis,” Diabetes Care, vol. 38, no. 12, pp. 2354–2369, 2015.
View at: Publisher Site | Google Scholar
F. F. Li, B. L. Liu, R. N. Yan et al., “Features of glycemic variations in drug naïve type 2 diabetic patients with different HbA_1c values,” Scientific Reports, vol. 7, no. 1, p. 1583, 2017.
View at: Publisher Site | Google Scholar

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Copyright © 2018 Ying Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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