Acute and Chronic Effect of Teriparatide on Glucose Metabolism in Women with Established Osteoporosis

Abstract

There is indirect evidence of unfavorable effects of parathyroid hormone (PTH) on glucose metabolism. Teriparatide (recombinant human PTH 1-34-TPTD) has recently been available for the treatment of osteoporosis. The aim of this prospective study was to evaluate the acute and chronic effect of TPTD on blood glucose and insulin levels in women with established osteoporosis. Twenty-three postmenopausal women with established osteoporosis (mean age 65.6±1.8 years) received daily injections of 20 mg TPTD for six months. Three oral glucose tolerance tests (OGTT) were performed: one day before the first injection (OGTT-basal), one hour after (OGTT-acute) and six months after initiation of therapy (OGTT-chronic). There were significant differences between the OGTT-basal and OGTT-acute values in glucose at 90 min (168.3±9.8 vs. 180.6±9.2, p<0.05) and 120 min (152.0±8.7 vs. 170.5±7.8, p<0.01), between the OGTT-basal and OGTT-chronic values for glucose at 90 min (168.3±9.8 vs. 184.5±13.3, p<0.05) and between the OGTT-basal and OGTT-acute for insulin at 90 min (56.7±7.4 vs. 68.7±8.2, p<0.01). These differences remained significant for the subgroup of patients with normal (n=8) but not impaired glucose tolerance or diabetes mellitus (n=15). TPTD seems to have an acute, subclinical adverse impact on stimulated glucose levels, possibly due to insulin resistance. This impact tends to subside when TPTD is continued on a chronic basis.

Key words

teriparatide - glucose metabolism - diabetes mellitus - impaired glucose tolerance - parathyroid hormone

References

• 1 Chiu KC, Chuang LM, Lee NP, Ryu JM, McGullam JL, Tsai GP, Saad MF. Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level.  Metabolism. 2000;  49 1501-1505
• 2 Fadda GZ, Akmal M, Lipson LG, Massry SG. Direct effect of parathyroid hormone on insulin secretion from pancreatic islets.  Am J Physiol. 1990;  258 975-984
• 3 Fliser D, Franek E, Fode P, Stefanski A, Schmitt CP, Lyons M, Ritz E. Sub-acute infusion of physiological doses of parathyroid hormone raises blood pressure in humans.  Nephrol Dial Transplant. 1997;  12 933-938
• 4 Kumar S, Olukoga AO, Gordon C, Mawer EB, France M, Hosker JP, Davies M, Boulton AJ. Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism.  Clin Endocrinol (Oxf). 1994;  40 47-53
• 5 Mak RH, Bettinelli A, Turner C, Haycock GB, Chantler C. The influence of hyperparathyroidism on glucose metabolism in uremia.  J Clin Endocrinol Metab. 1985;  60 229-233
• 6 Nowicki M, Fliser D, Fode P, Ritz E. Changes in plasma phosphate levels influence insulin sensitivity under euglycemic conditions.  J Clin Endocrinol Metab. 1996;  81 156-159
• 7 Prager R, Kovarik J, Schernthaner G, Woloszczuk W, Willvonseder R. Peripheral insulin resistance in primary hyperparathyroidism.  Metabolism. 1983;  32 800-805
• 8 Prager R, Schernthaner G, Kovarik J, Cichini G, Klaushofer K, Willvonseder R. Primary hyperparathyroidism is associated with decreased insulin receptor binding and glucose intolerance.  Calcif Tissue Int. 1984;  36 253-258
• 9 Procopio M, Borretta G. Derangement of glucose metabolism in hyperparathyroidism.  J Endocrinol Invest. 2003;  26 1136-1142
• 10 Procopio M, Magro G, Cesario F, Piovesan A, Pia A, Molineri N, Borretta G. 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
• 11 Richards ML, Thompson NW. Diabetes mellitus with hyperparathyroidism: another indication for parathyroidectomy?.  Surgery. 1999;  126 1160-1166
• 12 Saxe AW, Gibson G, Gingerich RL, Levy J. Parathyroid hormone decreases in vivo insulin effect on glucose utilization.  Calcif Tissue Int. 1995;  57 127-132
• 13 Taylor WH, Khaleeli AA. Coincident diabetes mellitus and primary hy-perparathyroidism.  Diabetes Metab Res Rev. 2001;  17 175-180
• 14 Thomas DM, Rogers SD, Sleeman MW, Pasquini GM, Bringhurst FR, Ng KW, Zajac JD, Best JD. Modulation of glucose transport by parathyroid hormone and insulin in UMR 106-01, a clonal rat osteogenic sarcoma cell line.  J Mol Endocrinol. 1995;  14 263-275
• 15 Valdermarsson S, Leckstrom A, Westermark P, Bergenfelz A. Increased plasma levels of islet amyloid polypeptide in patients with primary hyperparathyroidism.  Eur J Endocrinol. 1996;  134 320-325
• 16 Westerdahl J, Valdemarsson S, Lindblom P, Bergenfelz A. Urate and arteriosclerosis in primary hyperparathyroidism.  Clin Endocrinol (Oxf). 2001;  54 805-811
• 17 Zablocki K, Michalik M, Bryla J. Substrate-dependent effect of 1-34 human parathyroid hormone fragment, dibutyryl cAMP and cAMP on gluconeogenesis in rabbit renal tubules.  Biochim Biophys Acta. 1986;  886 483-490

Correspondence