The Effect of Parathyroidectomy on Insulin Sensitivity in Patients with Primary Hyperparathyroidism – an never Ending Story?

Abstract

Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT.

Key words

PTH - calcium - clamp - homa - ISI - surgery

• References

• 1 Kautzky-Willer A, Pacini G, Niederle B et al. Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery. Clin Endocrinol 1992; 37: 147-155
• 2 Procopio M, Magro G, Cesario F et al. The oral glucose tolerance test reveals a high frequency of both impaired glucose tolerance and undiagnosed type 2 diabetes mellitus in primary hyperparathyroidism. Diabet Med 2002; 19: 958-961
• 3 Cheung PS, Thompson NW, Brothers WE et al. Effect of hyperparathyroidism on the control of diabetes mellitus. Surgery 1986; 100: 1039-1047
• 4 Ljunghall S, Palmaer M, Akerstreom G et al. Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy. Eur J Clin Invest 1983; 13: 373-377
• 5 Lundgren E, Ljunghall S, Akerstrom G et al. Case-control study on symptoms and signs of ‘asymptomatic’ primary hyperparathyroidism. Surgery 1998; 124: 980-986
• 6 Garcia De la Torre N, Wass JAH, Turner HE. Parathyroid adenomas and cardiovascular risk. Endocrine-related cancer 2003; 10: 309-322
• 7 Bolland MJ, Grey AB, Gamble GD et al. Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J Clin Endocrinol Metab 2005; 90: 1525-1530
• 8 Procopio M, Barale M, Bertaina S et al. Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and their correlation to different clinical forms. Endocrine 2014; 47: 581-589
• 9 Luigi P, Chiara FM, Laura Z et al. Arterial Hypertension, Metabolic Syndrome and Subclinical Cardiovascular Organ Damage in Patients with Asymptomatic Primary Hyperparathyroidism before and after Parathyroidectomy: Preliminary Results. Int J Endocrinol 2012; 2012 408295 Epub 2012 Jun 7
• 10 Tassone F, Gianotti L, Baffoni C et al. Prevalence and characteristics of metabolic syndrome in primary hyperparathyroidism. J Endocrinol Invest 2012; 35: 841-846
• 11 Cardenas MG, Vigil KJ, Talpos GB et al. Prevalence of type 2 diabetes mellitus in patients with primary hyperparathyroidism. Endocr Pract 2008; 14: 69-75
• 12 Tassone F, Procopio M, Gianotti L et al. Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism. Diabet Med 2009; 26: 968-973
• 13 Yamaguchi T, Kanazawa I, Takaoka S et al. Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus. Metabolism 2011; 60: 1334-1339
• 14 Chiu K, Chuang LM, Lee N et al. Insulin sensitivity is inversely correlated with plasma intact parathyroid horemone level. Metabolism 2000; 49: 1501-1505
• 15 Ayturk S, Gursoy A, Tutuncu NB et al. Changes in insulin sensitivity and glucose and bone metabolism over time in patients with asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab 2006; 91: 4260-4263
• 16 Cakir I, Unluhizarci K, Tanriverdi F et al. Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism. Endocrine 2012; 42: 419-422
• 17 Bollerslev J, Rosen T, Mollerup C et al. and on behalf of SIPH Study Group . Effect of surgery on cardiovascular risk factors in mild primary hyperparathyroidism. J Clin Endocrinol Metab 2009; 94: 2255-2261
• 18 Almqvist EG, Bondeson AG, Bondeson L et al. Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy. Scand J Clin Lab Invest 2012; 72: 92-99
• 19 Bhadada SK, Bhansali A, Shah VN et al. Changes in serum leptin and adiponectin concentrations and insulin resistance after curative parathyroidectomy in moderate to severe primary hyperparathyroidism. Singapore Med J 2011; 52: 890-893
• 20 Rudman A, Pearson ER, Smith D et al. Insulin resistance before and after parathyroidectomy in patients with primary hyperparathyroidism – a pilot study. Endocr Res 2010; 35: 85-93
• 21 Ishay A, Herer P, Luboshitzky R. Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism. Endocr Pract 2011; 17: 584-590
• 22 Gianotti L, Piovesan A, Croce CG et al. Interplay between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism. Calcif Tissue Int 2011; 88: 231-237
• 23 Prager R, Schernthaner G, Niederle B et al. Evaluation of glucose tolerance, insulin secretion, and insulin action in patients with primary hyperparathyroidism before and after surgery. Calcif Tissue Int 1990; 46: 1-4
• 24 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462-1470
• 25 Chen M, Porte Jr D. The effect of rate and dose of glucose infusion on the acute insulin response in man. J Clin Endocrinol Metab 1976; 42: 1168-1175
• 26 DeFronzo RA. Glucose intolerance and aging: evidence for tissue insensitivity to insulin. Diabetes 1979; 28: 1095-1101
• 27 Ferrannini E, Vichi S, Beck-Nielsen H et al. Insulin action and age: European Group for the Study of Insulin Resistance (EGIR). Diabetes 1996; 45: 947-953 1976; 42: 1168–1175
• 28 Amati F, Dube J, Coen P et al. Physical inactivity and obesity underlie insulin resistance of aging. Diabetes Care 2009; 32: 1547-1549
• 29 Bolland M, Grey A, Gamble G et al. Association between primary hyperparathyroidism and increased body weight: A meta-analysis. J Clin Endocrinol Metab 2005; 90: 1525-1530
• 30 Hagstrom E, Hellman P, Lundgren E et al. Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinemic clamp in a community-based cohort. Diabetologia 2007; 50: 317-324
• 31 DeFronzo RA, Lang R. Hypophosphatemia and glucose intolerance: evidence for tissue insensitivity to insulin. N Engl J Med 1980; 303: 1259-1263
• 32 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: 734-739
• 33 Kumar S, Olukoga AO, Gordon C et al. Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism. Clin Endocrinol (Oxf) 1994; 40: 47-53
• 34 Micic D, Cvijovic G, Doknic M et al. Effect of 12 months of recombinant human growth hormone replacement therapy on insulin sensitivity in GH-deficient adults as determined by different methods. J Postgrad Med 2002; 48: 260-265
• 35 Fernandez-Real JM, Izquierdo M, Ortega F et al. The relationship of serum calcitonin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab 2009; 94: 237-245
• 36 Kindblom JM, Ohlsson C, Ljungren O et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 2009; 24: 785-791
• 37 Hwang YC, Jeong IK, Ahn KJ et al. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle aged male subjects. Diab Metab Res Rev 2009; 25: 768-772
• 38 Kanazawa I, Yamaguchi T, Tada Y et al. Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes. Bone 2011; 48: 720-725
• 39 Hwang YC, Jeong IK, Ahn KJ et al. Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level. Osteoporosis Int 2012; 23: 1337-1342
• 40 Gagnon C, Lu ZX, Magliano DJ et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study). Diabetes Care 2011; 34: 1133-1138
• 41 Anderson JL, May HT, Horne BD et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010; 106: 963-968
• 42 Chacko S, Song Y, Manson JE et al. Serum 25-hydroxyvitamin D concentrations in relation to cardiometabolic risk factors and metabolic syndrome in postmenopausal women. Am J Clin Nutr 2011; 94: 209-217
• 43 Bril F, Maximos M, Portillo-Sanchez P et al. Relationship of Vitamin D with insulin resistance and disease severity in nonalcoholic steatohepatitis. J Hepatol 2015; 62: 405-411
• 44 Farahnak P, Larfars G, Sten-Linder M et al. Mild primary hyperparathyroidism: vitamin D deficiency and cardiovascular risk markers. J Clin Endocrinol Metab 2011; 96: 2112-2118
• 45 Norenstedt S, Pernow Y, Brismar K et al. Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of randomized double-blind study. Eur J Endocrinol 2013; 169: 795-804