Assessment of Insulin Resistance in Acromegaly Associated with Diabetes Mellitus before and after Transsphenoidal Adenomectomy.

Wasada, Taro; Aoki, Kaori; Satô, Akiko; Katsumori, Kozo; Muto, Kazuko; Takahashi, Osamu; Yokoyama, Hiroyuki; Iwasaki, Naoko; Babazono, Tetsuya; Takahashi, Chiaki; Iwamoto, Yasuhiko; Omori, Yasue; Hizuka, Naomi

doi:10.1507/endocrj.44.617

Cited by 36 publications

(41 citation statements)

References 11 publications

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“…Normalization of glucose tolerance in the present study was accompanied by an impressive improvement in insulin sensitivity, as shown by significant changes in both HOMA ISI and OGTT ISI . This is in agreement with the findings of studies based on the euglycaemic clamp (26,27) and with recent data on short-term postoperative HOMA ISI (30). Taken together, these results suggest that insulin sensitivity can improve quite quickly after surgery, whereas normalization of glucose tolerance in patients with acromegaly requires a sustained improvement of GH/IGF-I hypersecretion and insulin sensitivity.…”

Section: Discussionsupporting

confidence: 91%

“…Of note, glucose tolerance also normalized in patients with preoperative glucose intolerance or diabetes mellitus (23). Similarly, a marked postoperative improvement in insulin sensitivity, accompanied by a complete reversal of related glucose and lipid metabolism abnormalities, had been demonstrated previously in a small series of patients with acromegaly, by means of methodology based on a euglycaemic clamp (26,27). The difficulty of assessing insulin sensitivity with such sophisticated techniques, which hampers the study of large series, can be overcome by the use of variable indexes of insulin sensitivity (ISI), which can be simply deduced from measurements of plasma glycaemia and insulinaemia, obtained either in fasting conditions according to the homeostatic model assessment (HOMA) (28) or during an oral glucose tolerance test (OGTT) (29) -the latter index correlating best with data obtained by euglycaemic clamp (29).…”

Section: Introductionmentioning

confidence: 55%

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Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

Jaffrain-Rea

Minniti

Moroni

et al. 2003

European Journal of Endocrinology

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Background: Cardiac abnormalities develop in patients with acromegaly as a consequence of effects of GH/IGF-I on the heart and related cardiovascular risk factors. Objective: To evaluate the possible contribution of postoperative variations in blood pressure (BP), glucose tolerance and insulin sensitivity to the cardiac improvement reported in patients who have been cured of acromegaly. Design: Thirty-one patients with acromegaly were studied before and 6 months after successful transsphenoidal surgery, defined by normal age-related IGF-I concentrations and glucose-suppressed GH concentrations , 1 mg/l. Methods: Cardiovascular parameters were assessed by Doppler echocardiography and 24-h ambulatory blood pressure monitoring. Insulin sensitivity indexes were calculated on the basis of fasting and post-load glycaemia and insulinaemia and referred to as HOMA ISI and OGTT ISI , respectively. Results: Successful surgery was confirmed to improve left ventricular mass index (LVMI) and diastolic filling significantly. Mean 24-h systolic BP values decreased ðP ¼ 0:009Þ and BP rhythm was restored in 12 of 15 patients with a blunted preoperative profile. Glucose tolerance normalized in patients with preoperative glucose intolerance ðn ¼ 7Þ or diabetes mellitus ðn ¼ 3Þ: HOMA ISI and OGTT ISI increased (P ¼ 0:0001 for each parameter), indicating a marked improvement in insulin sensitivity. The postoperative reduction in LVMI correlated with increased insulin sensitivity (P , 0:001 for both indexes), but not with other parameters. Improved diastolic filling correlated with the reduction in LVMI. Conclusions: Successful surgery in patients with acromegaly induces a significant improvement in haemodynamic and metabolic risk factors. This study suggests a direct link between insulin resistance and acromegalic cardiomyopathy.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 55%

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

Jaffrain-Rea

Minniti

Moroni

et al. 2003

European Journal of Endocrinology

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“…A well-known major cause of glucose intolerance in acromegaly is insulin resistance (10)(11)(12) induced by growth hormone and its mediator, insulin-like growth factor type 1. Other risk factors (e.g., a long duration of active acromegaly and older patient age) may promote the development of glu-cose intolerance.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for glucose intolerance in active acromegaly

Kréze

Kreze-Spirova

Mikulecký

2001

Braz J Med Biol Res

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In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33%) had diabetes mellitus and 2 (5%; 1-16%) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

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“…CHRONIC growth hormone (GH) excess seems to induce a reduction of insulin sensitivity and worsening of glucose intolerance [1], and approximately 20% of acromegalic patients have diabetes mellitus [2]. Both marked improvements in insulin resistance and reduction of glycosylated hemoglobin (HbA1c) were reported to accompany postoperative decreases in GH level in these patients [3]. Although octreotide, which is the therapeutic agent used in the treatment of acromegaly, gradually reduces the GH level [4], it also inhibits the secretions of insulin, glucagon and other intestinal hormones.…”

mentioning

confidence: 99%

“…Both marked improvements in insulin resistance and reduction of glycosylated hemoglobin (HbA1c) were reported to accompany postoperative decreases in GH level in these patients [3]. Although octreotide, which is the therapeutic agent used in the treatment of acromegaly, gradually reduces the GH level [4], it also inhibits the secretions of insulin, glucagon and other intestinal hormones.…”

mentioning

confidence: 99%

Deterioration of Glycemic Control during Octreotide LAR Treatment in an Acromegalic Japanese Patient with Type 2 Diabetes Mellitus

et al. 2007

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Abstract. We report a case showing deterioration of glycemic control during octreotide long-acting release (LAR) treatment in an acromegalic Japanese patient with type 2 diabetes mellitus. The patient did not show much improvement of insulin sensitivity (QUICKI; 0.33 before treatment, 0.35 during octreotide LAR treatment), and showed a significant reduction in early insulin secretion (insulinogenic index; 0.28 before treatment, 0.08 during octreotide LAR treatment) on 75 g oral glucose tolerance test (75gOGTT), despite decreases in GH and IGF-I levels during the course of octreotide LAR treatment. Postoperatively, both insulin sensitivity and early insulin secretion on 75gOGTT were improved (QUICKI 0.59, insulinogenic index 0.35). There are some reports that insulinogenic index is lower in most Japanese patients with type 2 diabetes mellitus and that early insulin secretions are significantly suppressed after administration of octreotide LAR. Although the influence of octreotide LAR on glucose metabolism varies among individuals, it is necessary to manage the deterioration of glucose tolerance during octreotide LAR treatment in acromegalic Japanese patients with decreased insulinogenic index. CHRONIC growth hormone (GH) excess seems to induce a reduction of insulin sensitivity and worsening of glucose intolerance [1], and approximately 20% of acromegalic patients have diabetes mellitus [2]. Both marked improvements in insulin resistance and reduction of glycosylated hemoglobin (HbA1c) were reported to accompany postoperative decreases in GH level in these patients [3]. Although octreotide, which is the therapeutic agent used in the treatment of acromegaly, gradually reduces the GH level [4], it also inhibits the secretions of insulin, glucagon and other intestinal hormones. Furthermore, octreotide delays gastrointestinal movement, which leads to a decrease in glucose absorption [5]. Thus, these effects of octreotide are known to influence glucose metabolism, and the changes in glucose tolerance in acromegalic patients receiving octreotide treatment vary with the individual. Here, we report an acromegalic patient showing deterioration of glucose tolerance during treatment with octreotide long-acting release (LAR), which was well tolerated and reduced mean 24-hour GH levels as effectively as multiple daily subcutaneous injections of octreotide [6], and glucose tolerance without octreotide improved following surgery for pituitary tumor. Case ReportA 46-year-old woman was admitted to our hospital for a work-up for diabetes mellitus in July 2004. Her father also had diabetes mellitus. On physical examination, her body mass index (BMI) was 20.7 kg/m 2 , blood pressure was 130/80 mmHg, and she showed acromegalic facies. Laboratory examinations were

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Assessment of Insulin Resistance in Acromegaly Associated with Diabetes Mellitus before and after Transsphenoidal Adenomectomy.

Cited by 36 publications

References 11 publications

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

Impact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly

Risk factors for glucose intolerance in active acromegaly

Deterioration of Glycemic Control during Octreotide LAR Treatment in an Acromegalic Japanese Patient with Type 2 Diabetes Mellitus

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