In comparison with group C, patients in group A had significantly higher serum TC, TG, LDL, and lower serum HDL. In group B, serum TC and LDL were significantly higher, whereas serum HDL was significantly lower than that in groups A and C. Serum TG was significantly higher in group B than in group C, whereas there was no significant difference in relation to group A (Fig. 2).
In group A, serum leptin showed a significant positive correlation with TSH (P=0.0001), TC (P=0.0001), and DBP (0.026), whereas it showed a significant negative correlation with FT3 (P=0.0001) and FT4 (P=0.004).
In the patients in group B, serum leptin showed a significant positive correlation with serum TC (P=0.0001), TG (P=0.041), and LDL (P=0.036) (Fig. 3), and a significant negative correlation with serum HDL (P=0.039).
Since its discovery over a decade ago, leptin has been established as a key regulator of energy balance. In addition, leptin plays an important role in the development of atherosclerosis and CVD 8.
Serum levels of lipids are found to increase in hypothyroidism and adipocytes express high levels of TSH receptors. As shown by many studies, serum levels of leptin were significantly higher in hypothyroidism 9.
Both overt and subclinical hypothyroidism are correlated with endothelial dysfunction, diastolic hypertension, dyslipidemia, atherosclerotic plaque progression, and instability 10.
In the current study, serum leptin was significantly higher in hypothyroid patients with normal glucose tolerance and hypothyroid prediabetic patients in comparison with the control group (P=0.0001). Similarly, Ibrahim et al. 11 showed that serum leptin in hypothyroid patients was significantly higher than that in euthyroid controls (P<0.05). Also, Kar and Sinha 12 found that serum leptin was significantly higher in hypothyroid patients than in controls (P<0.05).
The present study showed that serum leptin was significantly high in hypothyroid patients with prediabetes. In agreement with the results of the current study, Al-Daghri et al. 13 found that among men and women, serum leptin was significantly higher in those with prediabetes than in the controls (P=0.004 and 0.046, respectively). Also, Yang et al. 14 showed that plasma leptin levels were significantly higher in patients with impaired fasting glucose than in those with normal glucose tolerance (P<0.05). Li et al. 15 showed that a significant inverse association existed between serum leptin and β-cell function, and suggested that leptin plays a role in the development of insulin resistance and diabetes independent of metabolic syndrome.
In line with the present results, Chen et al. 9 showed that hypothyroid patients presented with significantly higher serum levels of TC, TG, LDL, and leptin compared with controls (P<0.05).
The current results showed that in hypothyroid prediabetic patients, serum TC, TG, and LDL were significantly higher and serum HDL was significantly lower than that in hypothyroid patients with normal glucose tolerance. In agreement with the results of the lipid profile of prediabetics in the present study, Kansal and Kamble 16 found that TC, LDL, TG, very-low-density lipoprotein, the TG/HDL ratio, and the LDL/HDL ratio were significantly increased in prediabetic individuals compared with normal healthy individuals, whereas HDL was significantly lower in prediabetic individuals compared with normal healthy individuals.
In addition to the dyslipidemia found in prediabetic hypothyroid patients, the present study showed that serum uric acid, DBP, and WC were significantly higher in hypothyroid patients with normal glucose tolerance and prediabetic hypothyroid ones in comparison with the control group, whereas there was no significant difference in serum uric acid, DBP, and WC between hypothyroid patients with normal glucose tolerance and those with prediabetes.
In the present study, in hypothyroid patients with normal glucose tolerance, serum leptin showed a significant positive correlation with TSH (P=0.0001), TC (P=0.0001), and DBP (P=0.026) and a significant negative correlation with FT3 (P=0.0001) and FT4 (P=0.004); also, TSH showed a significant positive correlation with LDL (P=0.001) and DBP (P=0.01) and a significant negative correlation with uric acid (P=0.03), whereas in hypothyroid prediabetic patients, serum leptin showed a significant positive correlation with serum TC (P=0.0001), TG (P=0.041), and LDL (P=0.036), whereas it showed a significant negative correlation with serum HDL (P=0.039).
In conjunction with these results, Balgi et al. 17 showed that TC, LDL, TG, and very-low-density lipoprotein were significantly increased in prediabetics, whereas HDL was significantly decreased in prediabetics compared with normal healthy individuals and concluded that prediabetics are highly prone to cardiovascular complications. Gutch et al. 18 found that serum TSH levels in participants with metabolic syndrome were significantly higher than those of the controls (P<0.001), suggesting a significant relation between TSH and metabolic syndrome, and highlights the association between hypothyroidism and metabolic syndrome.
The first limitation of this study is its small sample size. The second limitation is that thyroid status was classified in all patients on the basis of one blood test. Thus, some individuals with transient TSH elevations might have been misclassified. The third the causality between TSH and lipid levels can not be fully established.
A well-designed prospective research study will be necessary to address the relationship between TSH and lipid levels in prediabetics.
In the treatment of dyslipidemia in hypothyroid patients with prediabetes, thyroid function, especially the serum TSH level, should be monitored and maintained in the relatively low-normal range.
The author thanks the nursing staff and laboratory technicians in Endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, for their sincere cooperation.
Conflicts of interest
There are no conflicts of interest.
1. Cui H, López M, Rahmouni K. The cellular and molecular bases of leptin
and ghrelin resistance in obesity. Nat Rev Endocrinol 2017; 13:338–351.
2. Herrick JE, Panza GS, Gollie JM. Leptin
soluble receptor, and the free leptin
index following a diet and physical activity lifestyle intervention in obese males and females. J Obes 2016; 2016:8375828.
3. Facey A, Dilworth L, Irving R. A review of the leptin
hormone and the association with obesity and diabetes mellitus. J Diabetes Metab 2017; 8:3.
4. Sudharmadevi MK, Lekshminarayan V, Balakumaran LK, Trivikrama SK. Hyperleptinemia-an independent predictor of metabolic syndrome in the adult population in Kerala, India. Int J Res Med Sci 2016; 4:3988–3992.
5. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017; 390:1550–1562.
6. Huang Y, Cai X, Mai W, Li M, Hu Y. Association between prediabetes
and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ 2016; 355:i5953.
7. Cohen SL, Halaas JL, Friedman JM, Chait BT, Bennett L, Chang D, et al. Human leptin
characterization. Nature 1996; 382:589.
8. Denver RJ, Bonett RM, Boorse GC. Evolution of leptin
structure and function. Neuroendocrinology 2011; 94:21–38.
9. Chen Y, Wu X, Wu R, Sun X, Yang B, Wang Y, et al. Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism. Sci rep 2016; 6:26174.
10. Jabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol 2017; 14:39–55.
11. Ibrahim MK, Al-Samarrai AH, Khudhair KA. Association between leptin
hormone and thyroid hormone levels in hypothyroid
, hyperthyroid and euthyroid subjects. Front Biomed Sci 2016; 1:39–44.
12. Kar K, Sinha S. Variations of adipokines and insulin resistance in primary hypothyroidism. J Clin Diagn Res 2017; 11:BC07–BC09.
13. Al-Daghri NM, Al-Attas OS, Al-Rubeaan K, Mohieldin M, Al-Katari M, Jones AF, et al. Serum leptin
and its relation to anthropometric measures of obesity in pre-diabetic Saudis. Cardiovasc Diabetol 2007; 6:18.
14. Yang M, Peng S, Li W, Wan Z, Fan L, Du Y. Relationships between plasma leptin
receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population. Sci Rep 2016; 6:23948.
15. Li X, Zhao Y, Jin Y, Zhang T, Chang X, Liao S, et al. Associations between serum adipocytokines and glycemic tolerance biomarkers in a rural Chinese population. PLoS One 2017; 12:e0182273.
16. Kansal S, Kamble TK. Lipid profile in prediabetes
. J Assoc Physicians India 2016; 64:18–21.
17. Balgi V, Harshavardan L, Sahna E, Thomas SK. Pattern of lipid profile abnormality in subjects with prediabetes
. Int J Sci Res 2017; 4:150–153.
18. Gutch M, Rungta S, Kumar S, Agarwal A, Bhattacharya A, Razi SM. Thyroid functions and serum lipid profile in metabolic syndrome. BMJ 2017; 40:147–153.
Keywords:© 2018Wolters Kluwer Health Lippincott Williams Wilkins
cardiovascular risk; hypothyroid; leptin; prediabetes