Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study
Abstract
Background: Patients with primary hyperparathyroidism (PHPT) have increased mortality risk predominantly attributed to cardiovascular disease. Taking the risk factors for cardiovascular disease into account, such as overweight, atherogenic dyslipidaemia, carbohydrate metabolism disorders and insulin resistance (IR), investigation on the the study of the state of carbohydrate and lipid metabolism in patients with PHPT will help to shed light on the pathogenic mechanisms of the disease and, perhaps, to complement the algorithm for selecting treatment strategies for patients with PHPT.
Aims: To study the prevalence of carbohydrate and lipid metabolism disorders among patients with PHPT and to identify the relationship between these two disorders with the indicators of mineral metabolism.
Materials and methods: A case-control study of a total of age-matched 256 female patients, 220 patients with PHPT and 36 healthy individuals. The group patients with PHPT were sub-divided into two groups, symptomatic and mild form of PHPT. To verify the form of PHPT, ultrasound examinations of the parathyroid glands and kidneys, two-energy x-ray absorptiometry, biochemical studies (concentration of total and ionised calcium, serum phosphorus and the activity of alkaline phosphatase) and assessment of parathyroid hormone concentration were performed. The relationship between form of PHPT and body weight were evaluated retrospectively according to the survey. Among the 109 participants with PHPT (symptomatic PHPT: 82 patients; mild PHPT: 27 patients) and healthy individuals, the biochemical and hormonal parameters of fat (lipid spectrum of blood) and carbohydrate metabolism (content of immunoreactive insulin, HOMA index, presence of fasting glycemia disorder, glucose tolerance disorders and type 2 diabetes mellitus) were evaluated.
Results: The symptomatic PHPT was associated with low body mass index (BMI) while the mild PHPT with high BMI. During an oral glucose tolerance test, the postprandial glycemia in symptomatic PHPT was significantly higher than that in mild PHPT (p = 0.036). The content of immunoreactive insulin in the symptomatic PHPT was not correlated with the concentration of parathyroid hormone, but positively correlated with the concentration of ionised calcium in the blood (r = 0.31; p = 0.006). Patients with PHPT showed a direct positive correlation between BMI and IR index (r = 0.67; p < 0.001). It is shown that patients with PHPT have increased LDL content in the blood, and the actual blood lipid concentration is associated with the state of kidney function.
Conclusions: The obtained data confirm the relationship between phosphorus–calcium metabolism disorders in PHPT and carbohydrate and lipid metabolism disorders. Prospective, controlled studies are warranted to better elucidate the causal relationships of mineral, carbohydrate and fat metabolism disorders in PHPT.
About the Authors
Natalia G. MokryshevaEndocrinology Research Centre
Russian Federation
MD, PhD, Professor
Ekaterina A. Dobreva
Endocrinology Research Centre
Russian Federation
MD, PhD, senior research associate
Svetlana S. Mirnaya
Endocrinology Research Centre
Russian Federation
MD, research associate
Ivan I. Dedov
Endocrinology Research Centre
Russian Federation
MD, PhD, Professor
References
1. Вороненко И.В., Сыркин А.Л., Рожинская Л.Я., Мельниченко Г.А. Гиперпаратиреоз и патология сердечно-сосудистой системы // Остеопороз и остеопатиии. — 2006. — Т. 9. — №2. — С. 33-41. [Voronenko IV, Syrkin AL, Rozhinskaya LY, Mel'nichenko GA. Hyperparatirosis and cardiovascular system pathology. Osteoporosis and bone diseases. 2006;9(2):33-41. (In Russ.)] doi: https://doi.org/10.14341/osteo2006233-41
2. Мокрышева Н.Г. Первичный гиперпаратиреоз. Эпидемиология, клиника, современные принципы диагностики и лечения: Дис. … д-ра мед. наук. — М.; 2011. [Mokrysheva NG. Pervichnyy giperparatireoz. Epidemiologiya, klinika, sovremennye printsipy diagnostiki i lecheniya.[dissertation] Moscow; 2011. (In Russ.)]
3. Procopio M, Borretta G. Derangement of glucose metabolism in hyperparathyroidism. J Endocrinol Invest. 2003;26(11):1136-1142. doi: https://doi.org/10.1007/BF03345264
4. Tassone F, Procopio M, Gianotti L, et al. Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism. Diabet Med. 2009;26(10):968-973. doi: https://doi.org/10.1111/j.1464-5491.2009.02804.x
5. Thomas A, Kautzky-Willer A. Diabetes in Hyperparathyroidism. In: Ghigo E, Porta M, editors. Diabetes Secondary to Endocrine and Pancreatic Disorders. Front Diabetes. Vol 22. Basel: Karger; 2014. p. 92-100.
6. Temizkan S, Kocak O, Aydin K, et al. Normocalcemic hyperparathyroidism and insulin resistance. Endocr Pract. 2015;21(1):23-29. doi: https://doi.org/10.4158/EP14195.OR
7. Curione M, Letizia C, Amato S, et al. Increased risk of cardiac death in primary hyperparathyroidism: what is a role of electrical instability? Int J Cardiol. 2007;121(2):200-202. doi: https://doi.org/10.1016/j.ijcard.2006.08.072
8. McCarty MF, Thomas CA. PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses. 2003;61(5-6):535-542. doi: https://doi.org/10.1016/s0306-9877(03)00227-5
9. Delfini E, Petramala L, Caliumi C, et al. Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism. Metabolism. 2007;56(1):30-36. doi: https://doi.org/10.1016/j.metabol.2006.08.019
10. Lacour B, Roullet J-B, Liagre A-M, et al. Serum Lipoprotein Disturbances in Primary and Secondary Hyperparathyroidism and Effects of Parathyroidectomy. Am J Kidney Dis. 1986;8(6):422-429. doi: https://doi.org/10.1016/s0272-6386(86)80169-x
11. Christensson T, Einarsson K. Serum lipids before and after parathyroidectomy in patients with primary hyperparathyroidism. Clinica Chimica Acta. 1977;78(3):411-415. doi: https://doi.org/10.1016/0009-8981(77)90074-2
12. Erem C, Kocak M, Hacihasanoglu A, et al. Blood coagulation, fibrinolysis and lipid profile in patients with primary hyperparathyroidism: increased plasma factor VII and X activities and D-Dimer levels. Exp Clin Endocrinol Diabetes. 2008;116(10):619-624. doi: https://doi.org/10.1055/s-2008-1065365
13. Bonora E, Kiechl S, Willeit J, et al. Prevalence of insulin resistance in metabolic disorders: the Bruneck Study. Diabetes. 1998;47(10):1643-1649. doi: https://doi.org/10.2337/diabetes.47.10.1643
14. Bolland MJ, Grey AB, Gamble GD, Reid IR. Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J Clin Endocrinol Metab. 2005;90(3):1525-1530. doi: https://doi.org/10.1210/jc.2004-1891
15. Stampfer MJ. A Prospective Study of Triglyceride Level, Low-Density Lipoprotein Particle Diameter, and Risk of Myocardial Infarction. JAMA. 1996;276(11):882. doi: https://doi.org/10.1001/jama.1996.03540110036029
16. Krauss RM. Atherogenicity of Triglyceride-Rich Lipoproteins. Am J Cardiol. 1998;81(4):13B-17B. doi: https://doi.org/10.1016/s0002-9149(98)00032-0
17. Yener Ozturk F, Erol S, Canat MM, et al. Patients with normocalcemic primary hyperparathyroidism may have similar metabolic profile as hypercalcemic patients. Endocr J. 2016;63(2):111-118. doi: https://doi.org/10.1507/endocrj.EJ15-0392
18. Palaniappan L, Carnethon MR, Wang Y, et al. Predictors of the Incident Metabolic Syndrome in Adults: The Insulin Resistance Atherosclerosis Study. Diabetes Care. 2004;27(3):788-793. doi: https://doi.org/10.2337/diacare.27.3.788
19. Grundy SM, Hansen B, Smith SC, Jr., et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation. 2004;109(4):551-556. doi: https://doi.org/10.1161/01.CIR.0000112379.88385.67
20. Taylor WH, Khaleeli AA. Coincident diabetes mellitus and primary hyperparathyroidism. Diabetes Metab Res Rev. 2001;17(3):175-180. doi: https://doi.org/10.1002/dmrr.199
21. Schiffl H, Sitter T, Lang SM. Noradrenergic blood pressure dysregulation and cytosolic calcium in primary hyperparathyroidism. Kidney Blood Press Res. 1997;20(5):290-296. doi: https://doi.org/10.1159/000174161
22. Haap M, Heller E, Thamer C, et al. Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects. Eur J Clin Nutr. 2006;60(6):734-739. doi: https://doi.org/10.1038/sj.ejcn.1602375
23. World Health Organization. Definition, Diagnosis, and Classification of Diabetes Mellitus and its Complications: Report of a WHO consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva: WHO; 1999.
24. Ремизов О.В. Инсулинорезистентность у детей. Гормонально-метаболические аспекты патогенеза, профилактика и лечение СД 2 типа: Автореф. дис. … д-ра мед. наук. — М.; 2005. [Remizov OV. Insulinorezistentnost' u detey. Gormonal'no-metabolicheskie aspekty patogeneza, profilaktika i lechenie SD 2 tipa. [dissertation] Moscow; 2005. (In Russ.)]
25. Putnam R, Dhibar DP, Varshney S, et al. Effect of curative parathyroidectomy on insulin resistance. Indian J Endocrinol Metab. 2016;20(6):784-789. doi: https://doi.org/10.4103/2230-8210.192916
26. Cvijovic G, Micic D, Kendereski A, et al. The effect of parathyroidectomy on insulin sensitivity in patients with primary hyperparathyroidism - an never ending story? Exp Clin Endocrinol Diabetes. 2015;123(6):336-341. doi: https://doi.org/10.1055/s-0035-1549906
27. Taylor WH. The Prevalence of Diabetes Mellitus in Patients with Primary Hyperparathyroidism and Among Their Relatives. Diabet Med. 1991;8(7):683-687. doi: https://doi.org/10.1111/j.1464-5491.1991.tb01678.x
28. Dalberg K, Brodin LA, Juhlin-Dannfelt A, Farnebo LO. Cardiac function in primary hyperparathyroidism before and after operation. An echocardiographic study. Eur J Surg. 1996;162(3):171-176.
Supplementary files
|
1. Fig. 1. Changes in body weight on the background of primary hyperparathyroidism. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(45KB)
|
Indexing metadata ▾ |
|
2. Fig. 2. Communication of changes in body weight on the background of primary hyperparathyroidism with the concentration of parathyroid hormone (p <0.001) and Ca2 + (p <0.001). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(52KB)
|
Indexing metadata ▾ |
|
3. Fig. 3. Distribution of participants in the study from the main group according to body mass index, depending on the form of primary hyperparathyroidism. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(48KB)
|
Indexing metadata ▾ |
|
4. Fig. 4. Changes in body weight on the background of primary hyperparathyroidism among patients with different filtration kidney function (p = 0.009). | |
Subject | ||
Type | Исследовательские инструменты | |
View
(12KB)
|
Indexing metadata ▾ |
|
5. Fig. 5. Postprandial glycemia with oral glucose tolerance test, depending on the concentration of parathyroid hormone. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(24KB)
|
Indexing metadata ▾ |
Review
For citations:
Mokrysheva N.G., Dobreva E.A., Mirnaya S.S., Dedov I.I. Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study. Diabetes mellitus. 2019;22(1):8-13. (In Russ.)