Factors associated with an inadequate hypoglycemia in the insulin tolerance test in Japanese patients with suspected or proven hypopituitarism

We attempted to identify the predictors of an inadequate hypoglycemia in insulin tolerance test (ITT), defined as a blood glucose level higher than 2.8 mmol/L after insulin injection, in Japanese patients with suspected or proven hypopituitarism. A total of 78 patients who had undergone ITT were div...

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Published inEndocrine Journal Vol. 64; no. 4; pp. 387 - 392
Main Authors Nakamura, Akinobu, Kameda, Hiraku, Nagai, So, Shimizu, Chikara, Miyoshi, Hideaki, Atsumi, Tatsuya, Nomoto, Hiroshi, Terauchi, Yasuo, Taguri, Masataka, Cho, Kyu Yong, Takahashi, Kiyohiko
Format Journal Article
LanguageEnglish
Published Japan The Japan Endocrine Society 2017
Japan Science and Technology Agency
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Online AccessGet full text
ISSN0918-8959
1348-4540
DOI10.1507/endocrj.EJ16-0332

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Abstract We attempted to identify the predictors of an inadequate hypoglycemia in insulin tolerance test (ITT), defined as a blood glucose level higher than 2.8 mmol/L after insulin injection, in Japanese patients with suspected or proven hypopituitarism. A total of 78 patients who had undergone ITT were divided into adequate and inadequate hypoglycemia groups. The relationships between the subjects’ clinical parameters and inadequate hypoglycemia in ITT were analyzed. Stepwise logistic regression analysis identified high systolic blood pressure (SBP) and high homeostasis model assessment of insulin resistance (HOMA-IR) as being independent factors associated with inadequate hypoglycemia in ITT. Receiver operating characteristic (ROC) curve analysis revealed the cutoff value for inadequate hypoglycemia was 109 mmHg for SBP and 1.4 for HOMA-IR. The areas under ROC curve for SBP and HOMA-IR were 0.72 and 0.86, respectively. We confirmed that high values of SBP and HOMA-IR were associated with inadequate hypoglycemia in ITT, regardless of the degree of reduction of pituitary hormone levels. Furthermore, the strongest predictor of inadequate hypoglycemia was obtained by using the cutoff value of HOMA-IR. Our results suggest that HOMA-IR is a useful pre-screening tool for ITT in these populations.
AbstractList We attempted to identify the predictors of an inadequate hypoglycemia in insulin tolerance test (ITT), defined as a blood glucose level higher than 2.8 mmol/L after insulin injection, in Japanese patients with suspected or proven hypopituitarism. A total of 78 patients who had undergone ITT were divided into adequate and inadequate hypoglycemia groups. The relationships between the subjects' clinical parameters and inadequate hypoglycemia in ITT were analyzed. Stepwise logistic regression analysis identified high systolic blood pressure (SBP) and high homeostasis model assessment of insulin resistance (HOMA-IR) as being independent factors associated with inadequate hypoglycemia in ITT. Receiver operating characteristic (ROC) curve analysis revealed the cutoff value for inadequate hypoglycemia was 109 mmHg for SBP and 1.4 for HOMA-IR. The areas under ROC curve for SBP and HOMA-IR were 0.72 and 0.86, respectively. We confirmed that high values of SBP and HOMA-IR were associated with inadequate hypoglycemia in ITT, regardless of the degree of reduction of pituitary hormone levels. Furthermore, the strongest predictor of inadequate hypoglycemia was obtained by using the cutoff value of HOMA-IR. Our results suggest that HOMA-IR is a useful pre-screening tool for ITT in these populations.
Author Nagai, So
Nakamura, Akinobu
Atsumi, Tatsuya
Miyoshi, Hideaki
Kameda, Hiraku
Takahashi, Kiyohiko
Nomoto, Hiroshi
Cho, Kyu Yong
Shimizu, Chikara
Terauchi, Yasuo
Taguri, Masataka
Author_xml – sequence: 1
  fullname: Nakamura, Akinobu
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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  fullname: Kameda, Hiraku
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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  fullname: Nagai, So
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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  fullname: Shimizu, Chikara
  organization: Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
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  fullname: Miyoshi, Hideaki
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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  fullname: Atsumi, Tatsuya
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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  fullname: Nomoto, Hiroshi
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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  fullname: Terauchi, Yasuo
  organization: Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
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  fullname: Taguri, Masataka
  organization: Department of Biostatistics, Yokohama City University, Yokohama, Japan
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  fullname: Cho, Kyu Yong
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
– sequence: 1
  fullname: Takahashi, Kiyohiko
  organization: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
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10.1111/j.1365-2265.1979.tb02119.x
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10.1111/cen.12528
10.1111/j.1365-2265.1992.tb00946.x
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10.2337/diab.36.4.518
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Keywords Insulin tolerance test
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References 16. Longobardi S, Merola B, Pivonello R, Di Rella F, Di Somma C, et al. (1996) Reevaluation of growth hormone (GH) secretion in 69 adults diagnosed as GH-deficient patients during childhood. J Clin Endocrinol Metab 81: 1244-1247.
23. Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, et al. (1999) Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care 22: 818-822.
6. Ajala O, Lockett H, Twine G, Flanagan DE (2012) Depth and duration of hypoglycaemia achieved during the insulin tolerance test. Eur J Endocrinol 167: 59-65.
9. Fish HR, Chernow B, O’Brian JT (1986) Endocrine and neurophysiologic responses of the pituitary to insulin-induced hypoglycemia: a review. Metabolism 35: 763-780.
10. Burke CW (1992) The pituitary megatest: outdated? Clin Endocrinol (Oxf) 36: 133-134.
22. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, et al. (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23: 57-63.
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14. Smith D, Amiel SA (2002) The anatomy of the human hypoglycaemia sensor. Diabetes Nutr Metab 15: 316-318.
3. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E (2007) Hypopituitarism. Lancet 369: 1461-1470.
7. Committee of Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus, Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, et al. (2010) Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig 1: 212-228.
19. Kinoshita Y, Tominaga A, Usui S, Arita K, Sakoguchi T, et al. (2013) The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: a comparison. Endocr J 60: 97-105.
21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419.
5. Lange M, Svendsen OL, Skakkebaek NE, Muller J, Juul A, et al. (2002) An audit of the insulin-tolerance test in 255 patients with pituitary disease. Eur J Endocrinol 147: 41-47.
4. Lee P, Greenfield JR, Ho KK (2009) Factors determining inadequate hypoglycaemia during insulin tolerance testing (ITT) after pituitary surgery. Clin Endocrinol (Oxf) 71: 82-85.
20. Simsek Y, Karaca Z, Tanriverdi F, Unluhizarci K, Selcuklu A, et al. (2015) A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin Endocrinol (Oxf) 82: 45-52.
13. Amiel SA, Simonson DC, Tamborlane WV, DeFronzo RA, Sherwin RS (1987) Rate of glucose fall does not affect counterregulatory hormone responses to hypoglycemia in normal and diabetic humans. Diabetes 36: 518-522.
1. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML (2011) Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96: 1587-1609.
2. Erturk E, Jaffe CA, Barkan AL (1998) Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 83: 2350-2354.
8. Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27: 1487-1495.
11. Staub JJ, Noelpp B, Girard J, Baumann JB, Graf S, et al. (1979) The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia. Clin Endocrinol (Oxf) 10: 595-601.
12. Shah A, Stanhope R, Matthew D (1992) Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ 304: 173-174.
15. Jones SL, Trainer PJ, Perry L, Wass JA, Bessser GM, et al. (1994) An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year. Clin Endocrinol (Oxf) 41: 123-128.
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References_xml – reference: 5. Lange M, Svendsen OL, Skakkebaek NE, Muller J, Juul A, et al. (2002) An audit of the insulin-tolerance test in 255 patients with pituitary disease. Eur J Endocrinol 147: 41-47.
– reference: 9. Fish HR, Chernow B, O’Brian JT (1986) Endocrine and neurophysiologic responses of the pituitary to insulin-induced hypoglycemia: a review. Metabolism 35: 763-780.
– reference: 14. Smith D, Amiel SA (2002) The anatomy of the human hypoglycaemia sensor. Diabetes Nutr Metab 15: 316-318.
– reference: 1. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML (2011) Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96: 1587-1609.
– reference: 4. Lee P, Greenfield JR, Ho KK (2009) Factors determining inadequate hypoglycaemia during insulin tolerance testing (ITT) after pituitary surgery. Clin Endocrinol (Oxf) 71: 82-85.
– reference: 7. Committee of Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus, Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, et al. (2010) Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig 1: 212-228.
– reference: 16. Longobardi S, Merola B, Pivonello R, Di Rella F, Di Somma C, et al. (1996) Reevaluation of growth hormone (GH) secretion in 69 adults diagnosed as GH-deficient patients during childhood. J Clin Endocrinol Metab 81: 1244-1247.
– reference: 13. Amiel SA, Simonson DC, Tamborlane WV, DeFronzo RA, Sherwin RS (1987) Rate of glucose fall does not affect counterregulatory hormone responses to hypoglycemia in normal and diabetic humans. Diabetes 36: 518-522.
– reference: 21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412-419.
– reference: 23. Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, et al. (1999) Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care 22: 818-822.
– reference: 11. Staub JJ, Noelpp B, Girard J, Baumann JB, Graf S, et al. (1979) The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia. Clin Endocrinol (Oxf) 10: 595-601.
– reference: 18. Aimaretti G, Baffoni C, DiVito L, Bellone S, Grottoli S, et al. (2000) Comparisons among old and new provocative tests of GH secretion in 178 normal adults. Eur J Endocrinol 142: 347-352.
– reference: 8. Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27: 1487-1495.
– reference: 6. Ajala O, Lockett H, Twine G, Flanagan DE (2012) Depth and duration of hypoglycaemia achieved during the insulin tolerance test. Eur J Endocrinol 167: 59-65.
– reference: 22. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, et al. (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23: 57-63.
– reference: 10. Burke CW (1992) The pituitary megatest: outdated? Clin Endocrinol (Oxf) 36: 133-134.
– reference: 15. Jones SL, Trainer PJ, Perry L, Wass JA, Bessser GM, et al. (1994) An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year. Clin Endocrinol (Oxf) 41: 123-128.
– reference: 2. Erturk E, Jaffe CA, Barkan AL (1998) Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 83: 2350-2354.
– reference: 17. Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, et al. (1996) New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 134: 352-356.
– reference: 3. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E (2007) Hypopituitarism. Lancet 369: 1461-1470.
– reference: 12. Shah A, Stanhope R, Matthew D (1992) Hazards of pharmacological tests of growth hormone secretion in childhood. BMJ 304: 173-174.
– reference: 19. Kinoshita Y, Tominaga A, Usui S, Arita K, Sakoguchi T, et al. (2013) The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: a comparison. Endocr J 60: 97-105.
– reference: 20. Simsek Y, Karaca Z, Tanriverdi F, Unluhizarci K, Selcuklu A, et al. (2015) A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin Endocrinol (Oxf) 82: 45-52.
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Snippet We attempted to identify the predictors of an inadequate hypoglycemia in insulin tolerance test (ITT), defined as a blood glucose level higher than 2.8 mmol/L...
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SubjectTerms Adult
Asian Continental Ancestry Group
Blood glucose
Blood Glucose - analysis
Blood Pressure
Diagnostic Techniques, Endocrine
Female
Glucose
Homeostasis
Homeostasis model assessment of insulin resistance
Humans
Hypoglycemia
Hypoglycemia - diagnosis
Hypoglycemia - etiology
Hypoglycemia - metabolism
Hypoglycemia - physiopathology
Hypopituitarism
Hypopituitarism - complications
Hypopituitarism - diagnosis
Hypopituitarism - metabolism
Hypopituitarism - physiopathology
Insulin
Insulin Resistance
Insulin tolerance test
Japan
Male
Middle Aged
Pituitary
Pituitary hormones
Retrospective Studies
Risk Factors
Title Factors associated with an inadequate hypoglycemia in the insulin tolerance test in Japanese patients with suspected or proven hypopituitarism
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