A study of Sr. Fructosamine level, FPG and HbA1C level in the hypothyroid patients at tertiary health care centre

 

Pitchai Ansar Khalifullah¹, N Ananthi^2*

 

Abstract               Background: Thyroid disorders are very common in the general population and is second most common condition affecting the endocrine system after diabetes mellitus. Decreased production of thyroid hormone is the key feature of hypothyroidism. Aims and Objectives: To Study Sr. Fructosamine level, FPG and HbA1C level in the hypothyroid patients at tertiary health care centre. Methodology: This was a cross-sectional study carried out in the department of Biochemistry of a tertiary health care centre during the one year period i.e. March 2017 to March 2018 , in one year duration the diagnosed patients of Hypothyroidism (n=45) and Other eu-thyroid patients (n=45) were selected into the study after the written explained consent . All the patients undergone the investigations like FPG, HbA1C, Fructosamine biochemical tests carried out by standard biochemical procedures. All details of the patients like age, sex was noted. The statistical analysis was done by unaired t-test, and calculated by SPSP 19 version software. Result: In our study we have seen that the average age of the patients in both the groups was 49 ± 5.34 and 50± 4.57 (p >0.05, df=88, unpaired - t=1. 45) was comparable to each other. The Male: Female sex ratio was 2.33 and 3.44 was comparable to each other (X2=0.24, df=1,p>0.05).The parameters were significantly higher like ; FPG (mg/dl)-91.56±7.89 and 80.92 ±5.82 (t=7.28,df=88,p<0.0001); HbA1C-7.12± 3.45 and 5.34± 2.91 (t=9.83,df=88,p<0.0001); Fructosamine (μmol/L)-593.87±56.89 and 257.92±8.95 (t=5.73,df=88,p<0.001) in Hypothyroid group as compared to Euthyroid group respectively. Conclusion: It can be concluded from our study that FPG < HbA1C and Fructosamine were significantly higher in Hypothyroid group as compared to euthyroid group.

Key Word: FPG, HbA1C, Sr. Fructosamine, Hypothyroidism.

 

 

 

INTRODUCTION

Thyroid disorders are very common in the general population and is second most common condition affecting the endocrine system after diabetes mellitus. Decreased production of thyroid hormone is the key feature of hypothyroidism.^1,2 It is often complicated by conditions such as dilutional hyponatremia, anaemia and hyperlipidemia.^{3 4,5} The American Diabetes Association (ADA) have approved the use of HbA1c for the screening and the diagnosis of diabetes.6 The HbA1c concentration not only depends on prevailing glycaemia but also the life span of the erythrocytes and so, the conditions which affect the erythrocyte turnover or survival may lead to falsely elevate or lower the HbA1C levels.^7-11 So we have studied the hypothyroid and eu-thyroid patients for the various biochemical parameters .

 

 

METHODOLOGY

This was a cross-sectional study carried out in the department of Biochemistry of a tertiary health care centre during the one year period i.e. March 2017 to March 2018, in one year duration the diagnosed patients of Hypothyroidism (n=45) and Other euthyroid patients (n=45) were selected into the study after the written explained consent. All the patients undergone the investigations like FPG, HbA1C, Fructosamine biochemical tests carried out by standard biochemical procedures. All details of the patients like age, sex was noted. The statistical analysis was done by unaired t-test, and calculated by SPSP 19 version software.

RESULT

Table 1: Distribution of the patients as per age in two different group

The average age of the patients in both the groups was 49 ± 5.34 and 50± 4.57 (p >0.05, df=88, unpaired - t=1.45) was comparable to each other.

 

Table 2: Distribution of the patients as per the sex

The Male: Female sex ratio was 2.33 and 3.44 was comparable to each other (X²=0.24, df=1,p>0.05)

 

Table 3: Distribution of the patients as per the FPG, HbA1C, and Fructosamine with respect to thyroid status

The parameters were significantly higher like; FPG (mg/dl)-91.56±7.89 and 80.92 ±5.82 (t=7.28,df=88,p<0.0001); HbA1C-7.12± 3.45 and 5.34± 2.91 (t=9.83,df=88,p<0.0001); Fructosamine (μmol/L)-593.87±56.89 and 257.92±8.95 (t=5.73,df=88,p<0.001) in Hypothyroid group as compared to Euthyroid group respectively.

DISCUSSION

In hypothyroidism, there is a reduction in glucose-induced insulin secretion by beta cells, and the response of beta cells to glucose or catecholamine is increased in hyperthyroidism due to increased beta cell mass. Moreover, insulin clearance is increased in thyrotoxicosis Possibly, thence, diabetes and thyroid disorders have a propensity to appear together in patients¹² HbA1C is widely used for the assessment of glycemic status of the diabetic patients and the American Diabetes Association (ADA) recommended its use for diagnosing diabetes¹³. The glycated hemoglobin represents the fraction of hemoglobin that undergoes non-enzymatic glycation over the circulatory life span of the erythrocytes (usually 120 days)¹⁴ Two theories have been put forward to explain the increased levels of Hba1c levels in hypothyroid patients. One of those theories blames dysglycemia to be the cause of increased HbA1c levels. Various reasons have been put forward to explain the dysglycemia caused in hypothyroidism. Altered glucose homeostasis with decreased absorption and conversely decreased utilization also associated with hyper insulinemia and insulin resistance probably causing transient elevations in the glucose concentrations thus contributing to glycation of serum proteins¹⁵. Thyroid hormones have been shown to exert some of their actions synergically with insulin. The upregulation of the expression of genes such as GLUT-4 or phosphoglycerate kinase (PGK), involved in glucose transport and glycolysis respectively, is a good proof of concept. Therefore in hypothyroidism insulin resistance in peripheral tissue is present. Insulin resistance is the cause of increased glucose levels in hypothyroid levels.^16,17 Fructosamine orglycated albumin is best known for its use as a tool for assessing the glycaemic status, particularly in diabetics, where the glucose levels in plasma are high. All the hypothyroid cases had normal FPG values (88.63 ±10.33 mg/dl) as per the reference range (70-100 mg/dl), but the mean value was significantly higher as compared to that in the normal euthyroid controls (p=0.020). Despite the normoglycaemia of the hypothyroid patients, fructosamine was greatly increased in them, which could be due to the decreased turnover of the plasma proteins in hypothyroidism. Another approach to the explanation could be, the raised oxidant milieu in hypothyroidism^17,19. In hypothyroidism, the associated oxidative stress is the consequence of both the increased production of free radicals and the reduced capacity of the antioxidant defence. The enzyme, thyroperoxidase oxidizes iodide in the presence of H2O2 by using NADPH as a coenzyme. When the thyroid gland functions subnormally and when not enough iodination of the thyroid hormones takes place, the thyroid gland becomes a major site of a dangerous H2O2 generation. The cascade gets activated, resulting in raised TSH levels, thus increasing the production of H2O2, depleting the defense mechanisms like glutathione peroxidase, reducing the synthesis of T3 and T4, further increasing the TSH levels and worsening the functioning of the thyroid gland²⁰. Christ-Crain et al.,²¹, showed elevated C Reactive Protein (CRP) and homocysteine levels with progressive thyroid failure and postulated these as additional risk factors for the cardiovascular risk in hypothyroidism. Inflammation plays an important role in the progression and the complications of atherosclerosis. An inflammatory state, as is seen in hypothyroidism, adds to the generation of free radicals and the resultant ill effects of the same. When Segade et al.,²², and Fujita et al.,²³, studied the effects of different serum proteins on the fructosamine concentration, they found a significant correlation, not only with albumin, but also with the β and γ globulins, IgG, IgA, IgM and the total protein concentration. Any inflammatory process triggers the γ – globulin synthesis. The generation of free radicals in the inflammatory state, combined with the raised γ – globulins and the propensity of the γ – globulins to glycation, could be the basis of the increased glycation of the proteins in hypothyroidism. Hypothyroidism is also associated with hyperinsulinaemia²⁴. The slowed metabolic state of hypothyroidism not only slows the rate of glucose absorption from the gastro intestinal tract, but it also reduces the glucose utilization because of the insulin resistance^24,25. In the current study, the significantly higher FPG of this group in comparison with that of the reference group, pointed to the possibility that hyperinsulinaemia and insulin resistance may be causing small excursions in the glucose levels in the prandial and the post prandial states. In our study we have seen that the average age of the patients in both the groups was 49 ± 5.34 and 50± 4.57 (p >0.05, df=88, unpaired - t=1.45.) was comparable to each other. The Male : Female sex ratio was 2.33 and 3.44 was comparable to each other (X²=0.24, df=1,p>0.05) The parameters were significantly higher like; FPG (mg/dl)-91.56±7.89 and 80.92±5.82 (t=7.28,df=88,p<0.0001); HbA1C-7.12± 3.45 and 5.34± 2.91 (t=9.83,df=88,p<0.0001); Fructosamine (μmol/L)-593.87±56.89 and 257.92±8.95 (t=5.73,df=88,p<0.001) in Hypothyroid group as compared to Euthyroid group respectively. These findings are similar to Ram VS et al. ²⁶ et al they found that there was a positive correlation between the levels of serum TSH (µU/L) and HbA1c (%) in all the participants of the study by Pearson’s correlation coefficient (r=0.35, p < 0.0001). Also Sridevi V. Udup²⁷ they found that The fructosamine levels were significantly higher in Hypothyroid as compared to euthyroid group (p<0.05),

 

CONCLUSION

It can be concluded from our study that FPG < HbA1C and Fructosamine were significantly higher in Hypothyroid group as compared to euthyroid group.

 

REFERENCES

• Vij V, Chitnis P, Gupta VK. Evalution of thyroid dysfunction among type 2 diabetic patients. Int J Pharm Bio Sci. 2012; 2: 150-5.
• Joseph L. Radioisotopic evaluation of the thyroid and the parathyroids. In: Kronenberg H, Melmed S, Polonsky K, Larsen P, Price D, editors. Williams Textbook of Endocrinology. 11th ed. Philadelphia. Saunders, An Imprint of Elsevier; 2008:377-78.
• Antonijevi N, Nesovi M, Trbojevi B, Milosevi R. Anaemia in hypothyroidism. Med Pregl. 1999; 52(3- 5):136-40.
•  Cooper DS. Subclinical hypothyroidism. N Engl J Med. 2001; 345(4):260-5.
• Hueston WJ, Pearson WS. Subclinical hypothyroidism and the risk of hypercholesterolemia. annals of family medicine. Ann Fam Med. 2004; 2(4):351-5.
• American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011; 34(Suppl. 1):S62-69.
• World Health Organization Prevention and Control of Iron Deficiency Anaemia in Women and Children: Report of the UNICEF/ WHO Regional Consultation February 1999. Geneva, World Health Org; 2001.
• Fitzgibbons JF, Koler RD, Jones RT. Red cell agerelated changes of Haemoglobins A1a, A1b and A1C in normal and diabetic case. J Clin Invest. 1976; 58: 820-4.
• McGill JB, Bell DS. Anaemia and the role of erythropoietin in diabetes. J Diabet Complicat. 2006; 20: 262-72.
•  Gram-Hansen P, Eriksen J, Mourits-Andersen T, Olesen L. Glycosylated Haemoglobin (HbA1c) in iron and vitamin B12 deficiency. J Int Med. 1990; 227: 133-6.
• Hashimoto K, Noguchi S, Morimoto Y, Hamada S, Wasada K, Imai S, et al. A1C but not serum glycated albumin is elevated in late pregnancy owing to iron deficiency. Diabetes Care. 2008; 31(10):1945-8.
• Chaoxun  Wang.  The  Relationship  between  Type  2  Diabetes  Mellitus  and  Related  Thyroid  DiseasesJ Diabetes Res. 2013; 2013: 390534.
• Nima V. Thakkar and  Sunita M. JainThe Impact of  Diabetes  on  Thyroid  Dysfunction  and  Outcomes  in    Native  Indian  Female  PopulationThyroid  Science   6(4):1-9, 2011
• American   Diabetes   Association.Diagnosis   and   classification of  diabetes  mellitus.  Diabetes Care.  2010; 33:S62–69
• Nagraj Soni, G G Kaushik, VandanaYadav TO Study  lycemic  Status  and  Lipid  Fractions  In  Subclinical  Hypothyroid,  Overt  Hypothyroid And  Hyperthyroid  Subjects. International Journal of Advanced Research   (2014), Volume 2, Issue 9, 761-767
•  S. P. Weinstein, E. O’Boyle, and R. S. Haber, “Thyroid   hormone    increases    basal    and    insulin-stimulated glucose transport in skeletal muscle.  The role of GLUT4 glucose transporter expression,”Diabetes, vol. 43, no. 10, pp. 1185–1189, 1994.
• L. C. Moeller, A. M. Dumitrescu, R. L. Walker, P. S. Meltzer, and S. Refetoff, “Thyroid hormone responsive  genes  in  cultured  human  fibroblasts,”  Journal  of  Clinical  Endocrinology  &  Metabolism,  vol.  90, no.  2, pp.  936–943, 2005. View  at  Publisher
• Nanda N, Bobby Z, Hamide A. Oxidative stress and protein glycation in primary hypothyroidism, male/female difference. Clin Exp Med. 2008; 8: 101–08.
• Palanisamy P, Latha R. Free radical activity and antioxidant defense mechanisms in patients with hypothyroidism. Thyroid Science. 2008; 3(12):1-6
• Duntas LH. Selenium and the thyroid: A close knit connection. J Clin Endocrinol Metab. 2010;95:5180-88.
• Christ-Crain M, Meier C, Guglielmetti M, Huber PR, Riesen W, Staub JJ, et al. Elevated C- reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross- sectional and a double –blind placebo controlled trial. Atherosclerosis. 2003; 166: 379- 86.
• Segade SR, Lojo S, Camina FM, Paz MJ, Rio DR. Effects of various serum proteins on quantification of fructosamine. Clin Chem. 1989; 35(1):134-38.
• Fujita K, Curtiss LK, Sakurabayashi I, Kameko F, Okumura N, Terasawa F, et al. Identification and properties of glycated monoclonal IgA that affect fructosamine assay. Clin Chem. 2003; 49(5):805-08.
•  Singh BM, Goswami B, Mallika V. Association between insulin resistance and hypothyroidism in females attending a tertiary care hospital. Indian Journal of Clinical Biochemistry. 2010; 25(2):141-45.
• Chen G, Wu J, Lin Y, Huang B, Yao J, Jiang Q, Wen J, Lin L. Associations between cardiovascular risk, insulin resistance, b-cell function and thyroid dysfunction: a cross-sectional study in She ethnic minority group of Fujian Province in China. European Journal of Endocrinology. 2010; 163: 775-82
• Ram VS et al. Int J Res Med Sci. 2017 Aug;5(8):3345-3349
• Sridevi V. Udupa et al., Fructosamine and Lipids in Subclinical Hypothyroidism. Journal of Clinical and Diagnostic Research. 2013 January, Vol-7(1): 18-22.