|Year : 2018 | Volume
| Issue : 1 | Page : 48-53
Correlation of lipid profile among patients with hypothyroidism and type 2 diabetes mellitus
Amrita Ghosh1, Dipankar Kundu1, Faizur Rahman2, Md Ezaz Zafar2, KR Prasad2, HK Baruah2, Tapan Mukhopadhyay1
1 Department of Biochemistry, Medical College, Kolkata, West Bengal, India
2 Department of Biochemistry, Katihar Medical College, Katihar, Bihar, India
|Date of Submission||17-Nov-2017|
|Date of Acceptance||07-Feb-2018|
|Date of Web Publication||19-Jun-2018|
Dr. Amrita Ghosh
Demonstrator, Department of Biochemistry, Medical College, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
BACKGROUND: Dyslipidemia is common metabolic abnormality in thyroid disorders overt or subclinical and diabetes mellitus (DM) with a marked increase in circulating low-density lipoprotein (LDL-C).
OBJECTIVES: This study was carried out to find variations in dyslipidemic patterns in type 2 DM (T2DM) with hypothyroidism (HY).
METHODS: Total cholesterol (TC), triglycerides (TG), very low-density cholesterol (VLDL), low-density cholesterol (LDL), and high-density cholesterol (HDL) were compared among the three study groups at a tertiary care teaching hospital of Bihar in eastern India. Group A: T2DM. Group B HY, and Group C: having both T2DM and HY and control group.
RESULTS: The lipid profile of patients with diabetes showed TC (316.18 ± 4.299 mg/dl), TG (358.36 ± 5.544 mg/dl), LDL (214.70 ± 4.192 mg/dl), VLDL (71.67 ± 1.109 mg/dl), and HDL (29.80 ± 0.348 mg/dl). Mean lipid profile values in HYs were TC (314.38 ± 1.739 mg/dl), TG (322.46 ± 2.429 mg/dl), LDL (208.69 ± 1.665 mg/dl), VLDL (64.29 ± 0.5591 mg/dl), and HDL (41.20 ± 0.3647 mg/dl). Patients suffering from both diabetes and HY had TC (337.92 ± 4.793 mg/dl), TG (350.02 ± 5.127 mg/dl), LDL (236.17 ± 4.093 mg/dl), VLDL (70.01 ± 1.026 mg/dl), and HDL (31.74 ± 0.285 mg/dl). LDL value was markedly high in diabetic HY patients. All the lipid profile parameters were significantly increased except HDL among the patients with diabetes and HY patients. Increase was more in cholesterol and LDL values among patients suffering from both diabetes and HY. HDL levels were lowest among the patients with diabetes and also decreased among the diabetic HYs.
CONCLUSIONS: In this study, on patients with diabetes and HY, dyslipidemia was more in two variables, namely, cholesterol and LDL; there was a distinct difference in lipid profile patterns between single and dual morbidities.
Keywords: Dyslipidemia, hypothyroidism, type 2 diabetes mellitus
|How to cite this article:|
Ghosh A, Kundu D, Rahman F, Zafar ME, Prasad K R, Baruah H K, Mukhopadhyay T. Correlation of lipid profile among patients with hypothyroidism and type 2 diabetes mellitus. BLDE Univ J Health Sci 2018;3:48-53
|How to cite this URL:|
Ghosh A, Kundu D, Rahman F, Zafar ME, Prasad K R, Baruah H K, Mukhopadhyay T. Correlation of lipid profile among patients with hypothyroidism and type 2 diabetes mellitus. BLDE Univ J Health Sci [serial online] 2018 [cited 2019 May 23];3:48-53. Available from: http://www.bldeujournalhs.in/text.asp?2018/3/1/48/234645
“Diabetic dyslipidemia” is characterized by high level of plasma triglyceride (TG), and low-density lipoprotein (LDL) concentrations with low level of high-density cholesterol (HDL-c) due to the reduced action of insulin at the tissue level or due to insulin resistance. Diabetic dyslipidemia increases the risk of atherosclerosis, particularly, if glycemic control is poor, which in turn is an important risk factor for coronary heart disease. Hypothyroidism (HY) is also associated with hypercholesterolemia, hypertriglyceridemia with marked increased in circulating cholesterol concentration and LDL-C and apolipoprotein B (ApoB) due to decreased LDL receptor in the liver.,, In HY dyslipidemia, coexisting metabolic abnormalities in a combination of hormone-induced hemodynamic alterations lead to cardiovascular diseases. Thyroid dysfunction and DM are the two most common endocrine disorders. DM and thyroid disease appear to be closely linked. Thyroid hormone (TH) enhances the absorption, production, and utilization of glucose. Often, latent diabetes may be unmasked by hyperthyroidism, while hypoglycemia is sometimes a manifestation of HY. DM appears to influence thyroid function at several sites, from the hypothalamic control of TSH, release of T3, and production of T4 in the target tissue. The best studied effect is the lowering of circulating T3 in diabetics., Apart from genetic link between thyroid disorders and DM THs also have well-described effects on glucose and lipid metabolism. THs have short-term and long-term interactions with the regulatory network for energy homeostasis and through direct interaction with insulin, regulation causes glucose disposal in peripheral tissues. In the above scenario, the present study was conducted to find the lipoprotein alterations among patients suffering from HY, T2DM and having both these chronic morbidities.
| Methods|| |
This cross-sectional study was conducted on 150 participants in the Department of Biochemistry at a tertiary care teaching hospital in collaboration with the Department of Medicine from June 2012 to April 2014. The participants were allowed to pursue their treatment schedules and regular lifestyles during this study including drug intake, tobacco addiction. (Smokers were defined as consuming ≥5 cigarettes/day and were smoking continuously for a minimum of 6months before being enrolled. The patients who voluntarily participated in the study as cases and controls all hailed from comparable socioeconomic status, cultural standards, and food habits.
The participants in this study were recruited into three groups.
Group A consisted of 50 patients presented with only T2DM. Group B consisted of 50 patients who were suffering from only HY. Group C consisted of patients suffering from both T2DM and HY. Incidentally, some patients had preexisting HY, but many were newly diagnosed with HY during the study. Further, some patients presented with subclinical HY while others with overt HY.
Age- and gender-matched 50 apparently healthy persons were chosen as the control group.
Patients <18 years and suffering from or had indicative symptoms of diabetes and HY and other endocrinal/metabolic disorders, benign/malignant disorders, gastroenterological conditions and liver diseases, diabetic ketoacidosis, febrile conditions, renal diseases, transplant rejection, diseases of central nervous system, pregnant mothers, and HY arising as a result of thyroid surgery or radiotherapy.
Data collection procedure
Ethical clearance was obtained from the institution and permissions were taken from concerned authority before the commencement of the study. Informed consents were obtained from all individuals before participating in the study. Randomly selected diabetic patients were subjected to evaluation for thyroid function– clinically and biochemically. All the biochemical estimations were done using RFCL kit on the spectrophotometer. The diagnosis of DM was based on the World Health Organization criteria, i.e., a fasting plasma glucose of 126 mg/dl (7.0 mmol/L) after a minimum 12-hour fast, with symptoms of diabetes and 2 h postprandial glucose level of more than or equal to 200 mg/dl (11.1 mmol/L). Old patients with diabetes were confirmed for their present biochemical status. Postprandial samples were drawn 2 h following ingestion of 1.75 g per kg body weight with a maximum of 75 g of oral glucose in 300 ml of water. Fasting samples were used for the estimation of all the parameters except for the postprandial serum glucose estimation. Fasting and postprandial serum glucose was estimated quantitatively using GOD/POD technique as described by Trinder.
Serum free T3 (fT3), T4 (fT4), TSH were estimated using competitive enzyme-linked immunosorbent assay.,
Total cholesterol (TC) was estimated quantitatively by CHOD-PAP technique as described by Allian. Triacylglycerol was estimated quantitatively by GPO-ESPAS technique as described by Bucolo and David. High-density lipoproteins were estimated quantitatively by the PEG-PAP method. The lipid profile does not measure LDL level directly but instead estimates them using the Friedewald formula by subtracting the amount of cholesterol associated with other molecules, such as HDL and very low-density cholesterol (VLDL).,
Glycated hemoglobin was estimated from the whole blood by ion exchange method. The patients having both the conditions included in the study underwent other relevant investigations at first visit and on follow-up. All the observed data regarding patients were documented as per pro forma enclosed in the annexure and data protection was ensured.
Interpretation of the data was done by statistical software IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY and GraphPad Prism 7.1, 2018 GraphPad Software, Inc. (Trial version).
| Results|| |
This cross-sectional study was conducted to evaluate the alteration of the lipoprotein fractions within the group T2DM and HY and also compared among the study groups when both morbidities were present in the same study subjects. The mean and standard error of the mean (SEM) for lipoprotein parameters among all the study participants and healthy controls, i.e., TC, TGs, VLDL, LDL and HDL were compared among four groups Group A: Control, Group B: T2DM. Group C: HY, Group D: having both T2DM and HY.
Patients suffering from diabetes mellitus
The lipoprotein parameters were significantly increased among the diabetic patients except significantly decreased serum HDL level compared to control; also in T2DM group markedly increased TG level (358.36 ± 5.544 mg/dl) with lowest HDL level (29.80 ± 0.348 mg/dl).
The mean and SEM for TC in patients with diabetes was 316.18 ± 4.299 compared to control 178.74 ± 1.71.
The mean and SEM for TG in patients with diabetes was 358.36 ± 5.544 compared to control 190.50 ± 1.45.
Very low-density cholesterol
The mean and SEM for VLDL in patients with diabetes was 71.67 ± 1.109 compared to control 38.10 ± 0.289.
The mean and SEM for LDL in patients with diabetes was 214.70 ± 4.192 compared to control 103.02 ± 1.67.
The mean and SEM for HDL in patients with diabetes was 29.80 ± 0.348 compared to control 37.68 ± 0.293 [Table 1].
|Table 1: Lipoprotein alterations summarized among control in type 2 diabetes mellitus with hypothyroidism|
Click here to view
Patients suffering from hypothyroidism
All other parameters were significantly increased among the HY subjects including serum HDL level when compared to controls.
In our study subjects, the mean and SEM for TC in HYs was 314.38 ± 1.739 compared to control 178.74 ± 1.71.
In our study subjects, the mean and SEM for TG in HYs was 322.46 ± 2.429 compared to control 190.50 ± 1.45.
Very low-density cholesterol
In our study participants, the mean and SEM for VLDL in HYs was 64.29 ± 0.5591 compared to control 38.10 ± 0.289.
In our study participants, the mean and SEM for LDL in HYs was 208.69 ± 1.665 compared to control 103.02 ± 1.67.
In our study participants, the mean and SEM for HDL in HYs was higher 41.20 ± 0.3647 compared to control 37.68 ± 0.293 [Table 1].
Patients suffering from both hypothyroidism with diabetes mellitus
In this group, all the serum lipoprotein parameters were significantly increased except serum HDL level which was significantly decreased when compared to the controls.
In our study participants, the mean and SEM for TC in diabetic HYs was 337.92 ± 4.793 compared to control 178.74 ± 1.71.
In our study participants, the mean and SEM for TG in diabetic HYs was 350.02 ± 5.127 compared to control 190.50 ± 1.45.
Very low-density cholesterol
In our study participants, the mean and SEM for VLDL in diabetic HYs was 70.01 ± 1.026 compared to control 38.10 ± 0.289.
Low density cholesterol
In our study participants, the mean and SEM for LDL in diabetic HYs was 236.17 ± 4.093 compared to control 103.02 ± 1.67.
In our study participants, the mean and SEM for HDL in HYs was 31.74 ± 0.285 compared to control 37.68 ± 0.293 [Table 1].
ANOVA Bonferroni multiple comparisons test
The ANOVA Bonferroni multiple comparisons test was done among all the four groups of patients controls (A), DM only (B) or HY only (C), and DM with HY both (D). The results showed that except in TC and LDL values, all values were significantly different when compared between patients suffering either DM or HY. Further, except in triglyceride and VLDL values, all values were significantly different when compared between patients with DM only or suffering from both diabetes and HY. Although mean HDL value was higher in patients suffering from only HYs, yet the difference was significant in all the four groups of subjects including controls [Table 2].
|Table 2: Lipoprotein alterations among diabetics, hypothyroids, and healthy controls|
Click here to view
| Discussions|| |
Mean and SEM of TC, TG, VLDL, LDL, and HDL were compared among three study groups (T2DM, HY, and T2DM + HY) and control.
The lipoprotein parameters in our study were significantly increased among the diabetic subjects except serum HDL level which was significantly decreased. The lipid changes associated with DM are attributed to increased free fatty acid flux secondary to insulin resistance. The increased flux of free fatty acid into the liver in the presence of adequate glycogen stores promotes TG production which in turn stimulates the secretion of apoB and VLDL-cholesterol.
All lipid parameters were significantly increased among the HY subjects in this study compared to healthy controls even HDL level. Lipid synthesis, mobilization, and metabolism all are severely affected. The composition and transport of lipoproteins are also altered., Alteration of thyroid functions result in changes in the composition and transport of lipoproteins.,, Hence, there is often increase in serum TC concentration despite reduced activity of HMG CoA reductase enzyme due to elevated LDL and IDL levels., LDL level is increased due to decreased activity of receptor-mediated catabolism of LDL and IDL.,, Hypertriglyceridemia also occurs due to increased VLDL and fasting chylomicronemia but is less common. HY patients usually have high level of HDL mainly due to increased HDL-2 fraction. Decreased activity of the CTEP results in reduced transfer of cholesterol from HDL to VLDL, thus increasing HDL level. Further, there is decreased activity of hepatic lipase helping decreased catabolism of HDL-2 fraction and increase its level. Lipoprotein (a) which is a predictor of cardiovascular risk is also elevated in HY. These abnormalities of lipid metabolism are associated with OH predisposing to atherosclerotic coronary artery diseases.,
Hypothyroidism with diabetes mellitus
In our study in the HY with DM (T2DM + HY) group, all the serum lipoprotein parameters were significantly increased among the diabetic HY subjects except serum HDL level which was significantly decreased compared to controls. We have to bear in mind the close interface of metabolic control of these two chronic diseases demands recommendations for screening in higher risk groups like age over 50 or 55, particularly with suggestive symptoms such as dyslipidemia. The patients with HY demonstrate insulin resistance and dyslipidemia as observed by higher cholesterol and triglyceride levels. Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is an important risk factor for cardiovascular diseases. An Indian study reported that the level of HDL was significantly decreased and level of LDL, TG, and VLDL increased in subclinical and clinical HY diabetic patients as insulin sensitivity act as a mediator of thyroid induced lipid changes in diabetic patients. Jeong Rang Park noted that primary HY and type 2 diabetes were both typically associated with the increased level of TG.
| Conclusions|| |
In our study on patients of T2DM and HY, all lipid parameters, other than HDL, were significantly raised whether they had single or dual morbidity; dyslipidemia was more in two variables, namely, cholesterol and LDL. HDL levels were higher among HYs and decreased among patients with diabetes with or without HY. There was distinct difference of lipid profile patterns between single and dual morbidities; higher cholesterol and LDL levels were noted when the patients were suffering from both disease entities compared to controls and single disease.
The study suggests that there is also altered lipid profile among HY states, whether standalone cases or comorbid with DM which further aggravates risk of atherosclerotic pathologies. For that reason, regular screening for thyroid profile in DM as well as screening for DM among HYs should be incorporated in the clinical practice guidelines be helpful to reduce the risk of downstream risks of cardio vascular disease spectrum.
We express sincere benediction and thanks to all the patients and those healthy controls to carry out the painful investigations without any resentment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183-97.
Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 2009;5:150-9.
Elder J, McLelland A, O'Reilly DS, Packard CJ, Series JJ, Shepherd J, et al.
The relationship between serum cholesterol and serum thyrotropin, thyroxine and tri-iodothyronine concentrations in suspected hypothyroidism. Ann Clin Biochem 1990;27(Pt 2):110-3.
Staub JJ, Althaus BU, Engler H, Ryff AS, Trabucco P, Marquardt K, et al.
Spectrum of subclinical and overt hypothyroidism: Effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med 1992;92:631-42.
O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993;68:860-6.
Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: Value of annual screening. Diabet Med 1995;12:622-7.
Shah SN. Thyroid disease in diabetes mellitus. J Assoc Physicians India 1984;32:1057-9.
Bagchi N. Thyroid function in a diabetic population. Spec Top Endocrinol Metab 1982;3:45-55.
Peppa M, Koliaki C, Nikolopoulos P, Raptis SA. Skeletal muscle insulin resistance in endocrine disease. J Biomed Biotechnol 2010;2010:527850.
WHO Study Group. Diabetes Mellitus. Technical Report Series 727. Geneva: WHO; 1985.
Pedersen KO. Simultaneous determination of the free thyroxine and triiodothyronine fractions in serum. Scand J Clin Lab Invest 1974;34:241-6.
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-5.
Bhagat CI, Garcia-Webb P, Watson F, Beilby JP. Interference in radioimmunoassay of total serum thyroxin and free thyroxin due to thyroxin-binding autoantibodies. Clin Chem 1983;29:1324-5.
Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen receptor. Ann Clin Biochem 1969;6:24-7.
Bucolo G, David H. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 1973;19:476-82.
Izzo C, Grillo F, Murador E. Improved method for determination of high-density-lipoprotein cholesterol I. Isolation of high-density lipoproteins by use of polyethylene glycol 6000. Clin Chem 1981;27:371-4.
Warnick GR, Knopp RH, Fitzpatrick V, Branson L. Estimating low-density lipoprotein cholesterol by the friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints. Clin Chem 1990;36:15-9.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
Volpi N, Tarugi P. Improvement in the high-performance liquid chromatography malondialdehyde level determination in normal human plasma. J Chromatogr B Biomed Sci Appl 1998;713:433-7.
Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al.
Diabetes and cardiovascular disease: A statement for healthcare professionals from the American heart association. Circulation 1999;100:1134-46.
Chehade JM, Gladysz M, Mooradian AD. Dyslipidemia in type 2 diabetes: Prevalence, pathophysiology, and management. Drugs 2013;73:327-39.
Duntas LH. Thyroid disease and lipids. Thyroid 2002;12:287-93.
Heimberg M, Olubadewo JO, Wilcox HG. Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states. Endocr Rev 1985;6:590-607.
Babcock Irvin C, Wyer PC, Gerson LW. Preventive care in the emergency department, part II: Clinical preventive services – An emergency medicine evidence-based review. Society for academic emergency medicine public health and education task force preventive services work group. Acad Emerg Med 2000;7:1042-54.
Friis T, Pedersen LR. Serum lipids in hyper- and hypothyroidism before and after treatment. Clin Chim Acta 1987;162:155-63.
Stone NJ. Secondary causes of hyperlipidemia. Med Clin North Am 1994;78:117-41.
Walton KW, Scott PJ, Dykes PW, Davies JW. The significance of alterations in serum lipids in thyroid dysfunction. II. Alterations of the metabolism and turnover of 131-I-low-density lipoproteins in hypothyroidism and thyrotoxicosis. Clin Sci 1965;29:217-38.
Thompson GR, Soutar AK, Spengel FA, Jadhav A, Gavigan SJ, Myant NB, et al.
Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo
. Proc Natl Acad Sci U S A 1981;78:2591-5.
Abrams JJ, Grundy SM. Cholesterol metabolism in hypothyroidism and hyperthyroidism in man. J Lipid Res 1981;22:323-38.
Nikkilä EA, Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest 1972;51:2103-14.
Dullaart RP, Hoogenberg K, Groener JE, Dikkeschei LD, Erkelens DW, Doorenbos H, et al.
The activity of cholesteryl ester transfer protein is decreased in hypothyroidism: A possible contribution to alterations in high-density lipoproteins. Eur J Clin Invest 1990;20:581-7.
Lam KS, Chan MK, Yeung RT. High-density lipoprotein cholesterol, hepatic lipase and lipoprotein lipase activities in thyroid dysfunction – Effects of treatment. Q J Med 1986;59:513-21.
Tzotzas T, Krassas GE, Konstantinidis T, Bougoulia M. Changes in lipoprotein(a)levels in overt and subclinical hypothyroidism before and during treatment. Thyroid 2000;10:803-8.
Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al.
The spectrum of thyroid disease in a community: The whickham survey. Clin Endocrinol (Oxf) 1977;7:481-93.
Pucci E, Chiovato L, Pinchera A. Thyroid and lipid metabolism. Int J Obes Relat Metab Disord 2000;24 Suppl 2:S109-12.
Shashi A, Devi U, Singla S. Association between hypothyroidism and metabolic syndrome in type 2 diabetic patients: A cross sectional study. Int J Basic App Med Sci 2013;3:98-109.
Mason RL, Hunt HM, Hurxthal L. Blood cholesterol values in hyperthyroidism and hypothyroidism-their significance. N Engl J Med 1930;203:1273-8.
Taskinen MR. Diabetic dyslipidaemia: From basic research to clinical practice. Diabetologia 2003;46:733-49.
[Table 1], [Table 2]