Evaluation of renal function and subclinical hypothyroidism in persons with type 2 diabetes mellitus

 

 

Abstract               Background: Diabetic nephropathy due to diabetes is a major cause of end-stage renal disease. It is defined as raised urinary albumin excretion in absence of other kidney diseases that may increase risk of death, especially from cardiovascular causes. Thyroid dysfunction can have effect on development of diabetic nephropathy that have not been studied in a widespread way in India. Purpose is to compare subclinical hypothyroidism (SCH) with renal function in persons with type 2 diabetes mellitus (T2DM). Methods: In all the selected 215 subjects of type 2 diabetes mellitus, thyroid function screening was done by using ELFA method. These subjects were divided into two groups including T2DM with SCH (Group A) and T2DM without SCH (Group B). In all these subjects kidney function was assessed by estimating serum creatinine by Jaffe’s method and confirmation was done by eGFR using ID-MS traceable MDRD equation. Results: Significant difference between serum TSH, serum creatinine and eGFR was observed between the above said groups. Conclusion: Type 2 diabetic subjects with SCH can result in DN when compared to those without SCH and those with normal thyroid function.

Key Words: Diabetes Mellitus, HbA1c, SCH, serum TSH, serum FT4, serum creatinine, eGFR by MDRD.

 

 

INTRODUCTION

Diabetes, an endocrinal disorder is a group of metabolic disorders of carbohydrate metabolism producing hyperglycemia. It is increasing significantly worldwide.^1,2,3 which leads to an increase in development of microvascular complications like diabetic nephropathy (DN). End-stage renal disease (ESRD) may result because of DN, contributing to evidential increase in morbidity and mortality in persons with diabetes mellitus3. DN resulting from strong influence of thyroid hormones has excited the interests recently. Thyroid hormones have active role in regulation of kidney development, renal hemodynamics, GFR and sodium and water balance. Sub clinical hypothyroidism (SCH) can result in kidney dysfunction through decreased GFR, change in vascular and heart function and disturbance in Renin-Angiotensin system.^6,7,8

Several studies suggested.^9,10 That subclinical hypothyroidism is associated with evolution of microalbuminuria and DN. Many recent studies reported that low to normal thyroid hormones are linked with risk factors of DN like endothelial function, plasma lipid levels 7 hypertension. Other longitudinal studies ^13,14showed correlation between low-to-normal thyroid hormones and frequency of occurrence of macrovascular diseases. DN results in progressive loss of kidney function. Hence, it is necessary to recognize the risk factors of DN and track its evolution and progression, that will ameliorate the efficacy of treatment. This study is aimed to compare renal function with subclinical hypothyroidism. The study objectives are to

1.To estimate serum TSH, serum FT4, serum creatinine and eGFR in type 2 diabetes mellitus (T2DM) with and without subclinical hypothyroidism.

2.To compare serum TSH, serum FT4, serum creatinine, eGFR and HbA1c between the above said two groups.

 

MATERIAL AND METHODS

This study aimed to compare renal function in persons with T2DM with subclinical hypothyroidism (group A) and without subclinical hypothyroidism (group B). It included 215 adults, who attended OPD General Medicine, GSL General hospital, Rajahmundry, A.P., out of which 29 subjects were found to have subclinical hypothyroidism and 186 subjects were found to be without subclinical hypothyroidism. Thyroid function test is done by immunoassay and TSH value of 5 – 10 mIU/l with normal free T4 is considered as having subclinical hypothyroidism. In all subject’s kidney profile including serum creatinine and eGFR using MDRD formula was done. Anthropometric and hemodynamic details were obtained of all study subjects. Blood samples were used for estimation of HbA1c and serum creatinine. After 12 hours overnight fasting, samples were collected for TSH and FT4 estimations by standard immunoenzymatic procedures.

Inclusion criteria:

• Cases of known T2DM aged between 30 – 70 years.

Exclusion criteria:

• Cases of T1DM.
• Cases of non diabetic kidney diseases.
• Cases on nephrotoxic drugs.
• Cases with history of thyroid disorder or anti thyroid medications.
• Cases of diabetes mellitus with pregnancy.
• Cases of gestational diabetes mellitus.
• Cases with autoimmune diseases.
• Cases with acute chronic illness.

List of investigations done:

• HbA1c
• Serum TSH
• Serum FT4
• Serum creatinine

Renal function was screened by performing serum creatinine by alkaline picrate method and confirmation was done by eGFR using ID – MS traceable MDRD formula. Thyroid function was assessed by immunoassay using ELFA method. Informed consent was obtained from all study subjects, and the ethics committee of tertiary care hospital approved the study. Statistical analysis: was done using an online statistical software system, Graph Pad Prism and Microsoft excel 2007. Online Pearson’s correlation was applied to assess the association between thyroid hormones and DN. Data were expressed as mean ± SD. Statistical analysis included the unpaired t-test (for continuous measures). All known potential confounders (age, sex, HbA1c, serum TSH, serum FT4, serum creatinine) were entered in univariable model to ensure giving an unbiased estimate for the relation between subclinical hypothyroidism with DN and without DN. A p-value of < 0.05 was considered to be statistically significant.

 

RESULTS

Table 1 shows the age distribution of males and females. The minimum age in the male group was 32 years and the maximum age was 70 years, mean ± SD was 53.90 ± 10.06. Minimum age in the female group was 30 years and maximum age was 70 years, mean ± SD was 54.10 ± 10.99. Table 2 shows groups distribution among males and females. The number of males with T2DM with subclinical hypothyroidism were 9 and without subclinical hypothyroidism were 63. The number of females with T2DM with subclinical hypothyroidism were 20 and without subclinical hypothyroidism were 123. The percentage of type 2 diabetic males with subclinical hypothyroidism was 12.5 % and without subclinical hypothyroidism was 87.5 %. Among the female group, type 2 diabetic females with subclinical hypothyroidism was 13.98 % and without subclinical hypothyroidism was 86.01 %. Table 4 shows the biochemical parameters in diabetics with subclinical hypothyroidism (group A, n = 29) and diabetics without subclinical hypothyroidism group B, n = 186). The mean Serum TSH, Serum creatinine in group A was significantly higher than in group B (p < 0.0001, p = 0.004 respectively). The mean HbA1c and Serum FT4 however did not show any significance among the two groups. The mean eGFR in group A showed significantly lower levels when compared to Group B (p = 0.019).

 

Table 1: showing age distribution of males and females

Table 2: showing groups distribution among males and females

 

Table 3: Showing the biochemical parameters in diabetics with and without subclinical hypothyroidism (SCH)

 

DISCUSSION

In this study, we determined the comparison of renal function in persons with T2DM with and without SCH. Our results confer that type 2 diabetic subjects with SCH are proned to develop DN when compared with type 2 diabetic subjects without SCH. After lining up for likely risk factors of DN (age, sex, HbA1c levels, serum creatinine and eGFR) low to normal FT4 levels and high to normal TSH levels were significantly associated with decreased renal function. These findings suggest that low to normal thyroid hormone levels can be a likely risk factor for development of DN. Clinical studies have systematically showed that both poor control of glycemic status and hypertension are associated with DN. Another study reported that glycemic control (HbA1c level < 7%) was related with decreased microvascular injury. In our study we found that persons with poor control of glycemic status with SCH progressed to develop DN when compared to those without SCH. Other studies, in addition to traditional risk factors of DN, showed that thyroid function is related closely to the development of DN. Several studies²⁰, suggested increased prevalence of DN in diabetic patients who suffered from SCH or hypothyroidism. Further, replacement therapy with LT4 might decrease the risk of DN, like reducing uric acid levels, blood lipid, improving renal blood flow by raising GFR and slowing down the progression of kidney damage in such patients Clinical trials, showed that thyroid hormones are extremely related with secretion of insulin in euthyroid individuals. Other studies reported that increased insulin levels are related to decreased prevalence of DN in T2DM patients. Low thyroid hormone levels can directly result in DN by worsening vascular function³. Serum levels of FT3 have been shown related to endothelial dysfunction in patients with chronic kidney disease as determined by flow-mediated dilation. Patients with hypothyroidism and also those with SCH, go through endothelial dysfunction as a result of reduced availability of nitric oxide, that can be reversed by supplementation of LT_4. Endothelial dysfunction is considered to have an effect on initiation of DN, its progression and clinical sequelae. Other previous studies reported low thyroid hormone levels may occur in patients with serious illnesses. In patients with chronic kidney disease, low levels of FT3 have been regarded as independent predictor of mortality. With regard to the above data, it is suggested that low to normal thyroid hormone levels can be considered as a biomarker for DN and indicate accompanying prognosis of the patient. A study on patients with T2DM with euthyroid status demonstrated significant relation between high TSH levels and low to normal levels of thyroid hormones with magnified frequency of development of DN³ but our study showed high TSH levels and normal FT4 levels with increased incidence of decreased renal function in persons with T2DM. Study in Taiwan reported, in 588 T2DM subjects SCH was related to increased prevalence of DN and not diabetic retinopathy bur our study showed 215 T2DM subjects with 29 persons suffering from SCH were associated with increased progression of DN alone. The raised incidence of chronic kidney disease emphasize the need for further understanding the impact of thyroid hormone therapy. Studies in db/db mice suggested that T3 may prevent progressive damage to the kidney and remodelling by meliorating insulin signalling. Further research is recommended to dig into the involving association between SCH, DN and related complications.

 

CONCLUSION

The development of DN in type 2 diabetic persons with SCH is relatively common when compared with those without SCH and with those with normal thyroid function. Hence it is necessary to screen for thyroid function in persons with T2DM that may have an effect on renal function. Further research can dig into the causative association between SCH, DN and its complications by prospective and interventional studies.

 

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