Glucose Metabolism In Acromegaly Research Articles

Association of trabecular bone score corrected for tissue thickness with glucose metabolism in acromegaly.

Acromegaly is associated with increased vertebral fracture (VF) risk regardless of bone mineral density (BMD). However, the vertebral trabecular compartment is still low; a possible contributor to this may be impaired glucose metabolism (GM) which frequently complicates acromegaly. Additionally, soft tissue thickness may confound bone imaging in acromegaly patients. This study aims to assess the association of GM with BMD, trabecular bone score adjusted for BMI (TBSBMI), and trabecular bone score adjusted for tissue thickness (TBSTT) among acromegaly subjects. A cross-sectional study was performed among 70 consecutive acromegaly patients (24 male/46 female, aged 55.1 years) divided in two subgroups: abnormal GM (n = 35) and normal GM (n = 35). Using DXA, BMD, TBSBMI, TBSTT, and VF screening were performed. In all subjects, TBSTT was higher (mean 9.5%) than TBSBMI. Abnormal GM subjects had lower TBSBMI (1.166 ± 0.15) than normal GM subjects (1.232 ± 0.12; p < 0.05). No between-group difference in TBSTT or BMD was observed. In a multiple regression model, the best predictor of TBSTT was HbA1c (p = 0.002). None of the DXA measures or GM parameters was a significant predictor of VF (n = 7). The abnormal GM acromegaly subjects had lower TBSBMI than those with normal GM. TBSTT was higher than TBSBMI, and no between-group difference based on GM status was observed. TBSTT was significantly associated with GM parameters, notably HbA1c. The relationship of TBSTT with GM parameters may imply an effect of GM on trabecular bone microstructure in patients with acromegaly; a further study is indicated.

Prevalence of Abnormal Glucose Metabolism in Acromegaly &amp; Impact of Treatment Modalities on Glucose Metabolism

Objective: To determine the frequency of diabetes mellitus impaired glucose tolerance and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/ medical) on glucose metabolism.Methods: Eighty-nine patients fulfilling the endocrine society criteria for acromegaly diagnosis were included. A data of baseline, growth hormone (GH), Insulin-like growth factor-1 (IGF-1) level, Hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and random blood glucose (RBS) levels were reviewed before and after the intervention (surgery/medical therapy). Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were defined based on the 2003 ADA criteria. Patients were grouped into normoglycemic (NGT) and dysglycemic (IFG, IGT, and DM) based on FBS, RBS, and HbA1C. Results: Major risk factors for dysglycemia included age (15-45 years), male sex (33.70%), obesity (45.7%), and macroadenoma (76%). Both mean GH levels (58.29 vs. 54.36 ng/dl) and IGF-1 levels (862.98 vs. 824.32 ng/dl) were higher among the normoglycemic than dysglycemia. Pre-surgery, NGT, IFG, IGT, IFG, and IGT combined and DM were found in 48.31, 5.61, 1.1, 5.61, and 39.32 % of the subjects, respectively. Post-surgery, HbA1C improved in 79.5%, deteriorated in 6.8%, and remained the same in 13.6%. Similarly, it improved in 67.4.7% post-medical therapy. Both FBS and RBS improved post-surgery and medical therapy. Further, the number of anti-diabetic drugs used also decreased post-surgery. Conclusion: Dysglycemia is more common among patients with acromegaly as compared to the general population and tends to be poorly controlled in untreated acromegaly. Glycemic control improves significantly after the surgery and medical therapy.Keywords: Acromegaly, Diabetes Mellitus, Transsphenoidal surgery

Patterns of Abnormal Glucose Metabolism in Acromegaly and Impact of Treatment Modalities on Glucose Metabolism

Background: Chronic exposure to high levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) leads to metabolic complications, most importantly dysglycemia in the form of diabetes mellitus and pre-diabetes. Dysglycemia if diagnosed early in the course of the disease can decrease complications. Treatment modalities in the form of surgery and medical therapy have varied impacts on glucose metabolism.Objective: To determine the frequency of diabetes mellitus, impaired glucose tolerance, and impaired fasting glucose in Pakistani patients with acromegaly and to establish the impact of the intervention (surgery/medical) on glucose metabolism.Methods: This study was a retrospective review of patient records. Eighty-nine patients fulfilling the Endocrine Society criteria for acromegaly diagnosis were included. A data of baseline, GH, IGF-1 level, hemoglobin A1C (HbA1C), fasting blood glucose (FBG), and random blood glucose (RBS) levels were reviewed before and after the intervention (surgery/medical therapy). Normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were defined based on the American Diabetes Association (ADA) criteria. Patients were grouped into normoglycemic (NGT) and dysglycemic (IFG, IGT, and DM) based on FBG, RBS, and HbA1C.Results: Major risk factors for dysglycemia included age (15-45 years), male sex (33.70%), obesity (45.7%), and macroadenoma (77.52%). Both mean GH levels (58.29 vs. 54.36 ng/dl) and IGF-1 levels (862.98 vs. 824.32 ng/dl) were higher among the normoglycemic than dysglycemia. Pre-surgery NGT, IFG, IGT, IFG, and IGT/DM combined were found in 48.31%, 5.61%, 1.1%, 5.61%, and 39.32% of the subjects respectively. Post-surgery, HbA1C improved in 79.5%, deteriorated in 6.8%, and remained the same in 13.6%. Similarly, it improved in 67% post-medical therapy. Both FBG and RBS improved post-surgery and medical therapy. Further, the number of anti-diabetic drugs used also decreased post-surgery.Conclusion: Dysglycemia is more common among patients with acromegaly as compared to the general population and tends to be poorly controlled in untreated acromegaly. Glycemic control improves significantly after surgery and medical therapy.

Associations between circulating bone-derived hormones osteocalcin, lipocalin 2, and glucose metabolism in patients with acromegaly

Objective The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism. Methods Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables. Results Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P 0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 (β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin (β=0.512, P<0.01). In the multivariate models, low LCN2 (β=-0.398, P=0.017) and elevated serum osteocalcin (β=0.553, P=0.001) were predictors for AUCINS, osteocalcin was a positive predictor of HOMA- β (β=0.519, P=0.004). GH (β=0.294, P=0.029) and IGF-1(β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly. Key words: Acromegaly; Osteocalcin; Lipocalin 2; Glucose metabolism

Associations between circulating bone-derived hormones lipocalin 2, osteocalcin, and glucose metabolism in acromegaly.

The aim was to examine changes in the bone-derived hormone lipocalin 2 (LCN2) levels in patients with active acromegaly and to investigate the potential roles of LCN2 and osteocalcin in glucose metabolism. We recruited 50 consecutive acromegalic patients. Of those, 39 patients with complete postoperative follow-up data were included. Thirty sex-, age-, and BMI-matched healthy individuals were recruited as normal controls. The pre- and postoperative serum LCN2 and osteocalcin levels were compared. The homeostasis model assessment insulin resistance (HOMA-IR) index and secretion [β-cell function (HOMA-β)] were calculated. Compared with controls, acromegalic subjects had lower LCN2 levels (34.15 ± 9.95 vs 57.50 ± 29.75ng/mL, P < 0.01) and higher osteocalcin levels (55.45 ± 34.02 vs 19.46 ± 6.69ng/mL, P < 0.01). Acromegalic patients also had elevated HOMA-IR levels, and the HOMA-β and the area under the curve for insulin (AUC INS) levels were slightly but nonsignificantly increased. The serum levels of LCN2 significantly increased after surgery (37.03 ± 9.73 vs 45.15 ± 15.33ng/mL, P < 0.05), and those of osteocalcin significantly decreased [43.51 (26.73-65.66) vs 24.79 (18.39-32.59) ng/mL, P < 0.01]. Total lean mass was the only positive predictor of LCN2, and elevated serum IGF-I was a positive predictor of osteocalcin. Low LCN2 and elevated serum osteocalcin levels were predictors of the AUC INS, and osteocalcin was a positive predictor of HOMA-β. The bone-derived hormones, osteocalcin and LCN2 changed significantly in active acromegaly, were altered after treatment and served as predictors of β-cell function in acromegaly. This study shows that the bone could be involved in regulating glucose metabolism in acromegaly.

Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies

Pegvisomant (PEG) in monotherapy or combined with somatostatin analogs (SSAs) is used to control acromegaly, improving metabolism. However, the metabolic changes induced by PEG have not been systematically reviewed. To address the following questions: does PEG or the combination of PEG and SSAs affect fasting plasma glucose (FPG), glycosylated Hb (HbA1c), glucose load (2-hour oral glucose tolerance test), insulin levels [fasting plasma insulin (FPI)], homeostatic model assessment of insulin resistance (HOMA-I), homeostatic model assessment of β-cell function, lipid profile, or body mass index? Are the effects disease-related or drug-related? Indexed databases up to January 2019. Prospective interventional trials reporting glycometabolic outcomes under PEG or PEG plus SSAs for a minimum of 6 months. Three reviewers screened eligible publications (7248), three others extracted the outcomes, and all assessed the risk of biases. Thirteen studies were included in the PEG and 5 in the PEG plus SSAs analysis (overall 550 subjects). PEG significantly decreased FPG [effect size (ES) -0.80 mmol/L (95% CI, -1.06 to -0.55); P = 0.000], HbA1c [ES -0.43% (95% CI, -0.56 to -0.31); P = 0.000], FPI [ES -5.31 mU/L (95% CI, -10.23 to -0.39); P = 0.034], and HOMA-I [ES -0.61 (95% CI, -1.17 to -0.04); P = 0.034]. Effects on FPG and FPI were not correlated to IGF-1 changes. The addition of PEG to SSAs mitigated the effects of SSAs on metabolism, producing an overall neutral effect. Independently of disease control, PEG in monotherapy or combined with SSAs seems to improve glucose metabolism, reducing FPG, HbA1c, FPI, and HOMA-I.

Effects of pegvisomant on glucose metabolism in acromegaly: A meta-analysis of prospective interventional studies

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-analysis of Prospective Interventional Studies.

Somatostatin analogs (SSAs) effectivelycontrol growth hormone secretion in first and second line treatmentof acromegaly. Their effect onglucose metabolism is still debated. to address the following questions: 1) Do SSAs affect fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin (HbA1c), glucose load (2h-OGTT), HOMA-I, HOMA-β, triglycerides (TGD), weight (W) or body mass index (BMI)? 2) Do lanreotide (LAN) and octreotide LAR (OCT) affect metabolism differently? 3)Does their effect depend on disease control? We performed a meta-analysis of prospective interventional trialstreating acromegaly with SSAs. Inclusion criteria: all studies reporting glyco-metabolic outcomes before and after SSAs with a minimum 6-month follow-up. The inclusion criteria were met by 47 studies treating 1297 subjects (631 F). SSA treatment effectively lowered FPI (effect size [ES] -6.67 mU/L, 95%CI: -8.38 to -4.95mU/L; p<0.001), HOMA-I (ES -1.57, CI: -2.42 to -0.72; p<0.001), HOMA-β (ES -47.45, CI: -73.15 to -21.76; p<0.001) and TGD (ES -0.37 mmol/L, CI: -0.47 to -0.27 mmol/L; p<0.001). SSAs worsened 2h-OGTT (ES 0.59 mmol/L, CI: 0.05 to 1.13 mmol/L; p=0.032), but not FPG. A mild but significant increase in HbA1c (ES 0.12%, CI: 0.00to 0.25%; p=0.044) was found in OCT treated subjects. SSA treatment in acromegaly patients-while improving disease control- reduces insulin levels, increases after load glucose and, ultimately, increases HbA1c levels without affecting FPG. The findings suggest that clinicians treating acromegaly with SSAs should consider targeting post-prandial glucose.

Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study.

Purpose To evaluate the change in glucose tolerance in treatment-naïve patients with acromegaly after administration of SSA and to identify predictive factors of glucose impairment during SSA therapy. Methods Oral glucose tolerance testing (OGTT) was performed on 64 newly diagnosed and treatment-naïve patients with acromegaly both at pretreatment and 3 months after initiation of treatment with long-acting SSA. Insulin resistance (IR) was assessed by homeostatic model assessment- (HOMA-) IR and ISOGTT. Insulin secretion was assessed by HOMA-β, INS0/BG0, IGI (insulinogenic index), IGI/IR, ISSI2, and AUCINS/AUCBG. Receiver-operating characteristic (ROC) curves were generated to determine the optimal cutoffs to predict the impact of SSA on glucose metabolism. Results Pretreatment, 19, 24, and 21 patients were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM), respectively. Posttreatment, IR, represented by ISOGTT, was significantly improved in all 3 groups. Insulin secretion, represented by HOMA-β, declined in the NGT and IGT groups, but was unaltered in the DM group. The glucose tolerance status deteriorated in 18 (28.1%) patients, including 13 patients in the NGT group and 5 patients in the IGT group. Deterioration was associated with lower baseline BG120 (plasma glucose 120 min post-OGTT), less reduction of growth hormone (GH), and greater reduction of insulin secretion after SSA therapy. BG120 greater than 8.1 mmol/l provided the greatest sensitivity and specificity in predicting the stabilization and/or improvement of glucose tolerance status after SSA treatment (PPV 90.7%, NPV 66.7%, p < 0.001). Conclusions The deterioration of glucose metabolism induced by SSA treatment is caused by the less reduction of GH and the more inhibition of insulin secretion, which can be predicted by the baseline BG120 during OGTT.

Effects of Somatostatin Analogues on Glucose Metabolism in Acromegaly: Friend of Foe?

Effects of Somatostatin Analogues on Glucose Metabolism in Acromegaly: Friend of Foe?

Features of glucose metabolism in acromegaly depending on the type of treatment

Aim of the study was to investigate the features of glucose metabolism in patients with acromegaly depending on treatment. Materials and methods: 63 patients with acromegaly: 29 patients with newly diagnosed acromegaly, 25 patients receiving somatostatin analogs (SSA) therapy and 9 patients underwent surgical treatment. Patients with earlier revealed diabetes mellitus (DM) were not included. The characterization of glucose metabolism was carried out by means of an assessment of fasting insulin plasma levels (FIP) and indexes of an insulinresistance (IR) HOMA-R and an insulinsensivity (IS) MATSUDA. Results: In patients receiving SSA therapy the carbohydrate metabolism disorders (CMD) were revealed in 92%, among newly diagnosed acromegalic patients – in 62% and in patients after surgical treatment in 33% of cases. In newly diagnosed acromegalic patients index MATSUDA was 3,5 times lower than in patients receiving SSA therapy, and 4 times lower than in patients after surgical treatment ((р=0,001). НОМА-R in newly diagnosed acromegalic patients was 3,7 times higher than in other groups, p=0,003 and the level of FIP was 4,3 times higher than in patients receiving SSA therapy and 2,9 times higher than in patients after surgical treatment (р=0,001). The index MATSUDA in newly diagnosed acromegalic patients with early CMD was 2,9 times lower, р=0,006, НОМА-R – 2,5 times higher, р=0,025 and FIP 2,4 times higher, р=0,039 than in patients with early CMDs without acromegaly. Conclusions: In patients with newly diagnosed acromegaly in the absence of CMDs increase in IR is compensated by hyperinsulinemia. In patients, receiving SSA therapy the IR decreases, however suppression of secretion of insulin leads to increase in percentage of DM in this group. After surgical treatment IR decreases against higher level of fasting plasma insulin that leads to normalization of carbohydrate metabolism. Keywords: Acromegaly, secondary diabetes mellitus, insulinresistance, MATSUDA, HOMA-R.

Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic β-cell function is preserved

Impaired glucose metabolism is common in acromegaly, but it is not clear how glucose metabolism is impaired or what predicts its restoration after cure of the disease. To identify factors involved in the impairment of glucose metabolism in acromegaly, we evaluated clinical parameters before and immediately after surgical cure of the disease. We retrospectively analyzed clinical data of 92 consecutive Japanese patients with acromegaly who underwent successful pituitary surgery. Patients who had received medical therapy for acromegaly or insulin treatment for diabetes were excluded. We evaluated insulin resistance (IR) and pancreatic β-cell function in addition to GH and IGF1 levels before and after surgery. Results In this study of Japanese patients with acromegaly, average body mass index (BMI) was 23.4, and no patient had a BMI>30. IR was involved in the impairment of glucose metabolism, which was restored upon surgical cure of acromegaly if β-cell function was preserved. Insufficient β-cell function did not improve after normalization of GH/IGF1 and was associated with impaired glucose metabolism before and after surgery. of receiver operating characteristic analysis of preoperative clinical parameters suggest that insulinogenic index (IGI) >0.50 best predicts restoration of normal glucose metabolism upon cure of acromegaly in Japanese patients. IR impairs glucose metabolism in acromegaly. Once β-cell function is impaired, abnormal glucose metabolism persists even after cure of acromegaly. IGI>0.50 indicates that β-cell function is preserved in non-obese Japanese patients with acromegaly.

Impact of Somatostatin AnalogsVersusSurgery on Glucose Metabolism in Acromegaly: Results of a 5-Year Observational, Open, Prospective Study

The aim of the study was to investigate the 5-yr impact of surgery and somatostatin analogs (SSA) on glucose metabolism in acromegaly. We conducted an observational, prospective, comparative, nonrandomized study. The 100 patients (48 women, 52 men; median age, 49 yr) in the study were grouped as follows for treatment: SSA only (group A; n = 34); SSA followed by surgery (group B; n = 20); surgery only (group C; n = 30); and surgery followed by SSA (group D; n = 16). At diagnosis, 28% had impaired glucose tolerance, and 22% had diabetes mellitus; fasting glucose levels (4.13-10.60 mmol/liter) were best predicted by age (t = 2.88; P = 0.0049) and disease duration (t = 1.99; P = 0.049). After 60 months, fasting glucose levels reduced (-4.9 +/- 19.7%) in group A only, whereas they did not change in the other groups. In the 68 nondiabetic patients at baseline, fasting glucose levels increased by 0.7 +/- 11.2%, 7.5 +/- 10.3%, 4.3 +/- 10.4%, and 4.3 +/- 14.8% (P = 0.28), from groups A to D, respectively. Percentage change of fasting glucose in all patients receiving SSA was 1.9 +/- 12.3%, and in those not receiving SSA it was 6.4 +/- 10.8% (P = 0.13). Overall, prevalence of new onset of diabetes during SSA treatment was nine of 55 (16.4%) vs. three of 23 after surgery (13.0%, P = 0.98). Deterioration of glucose tolerance was correlated with increased body mass index (r = 0.49, P < 0.0001) and not with use of SSA or surgery (r = 0.06; P = 0.53), control or not of GH (r = -0.10, P = 0.31) and IGF-I (r = -0.12; P = 0.22). The results of this study demonstrate a similar deterioration of glucose tolerance after 60 months in patients receiving SSA or cured with surgery. Increase in body mass index was the major predictor of deterioration of glucose tolerance.

Low Serum IGF-I/GH Ratio Is Associated with Abnormal Glucose Tolerance in Acromegaly

Background/Aims: Acromegaly is frequently accompanied with impaired glucose tolerance (IGT) and diabetes mellitus (DM). It remains unclear which factors determine the abnormal glucose tolerance status in acromegaly. In addition, diverse actions of GH and IGF-I in regulating glucose metabolism in acromegaly have not yet been well elucidated. The aim of this study was to investigate the factors associated with abnormal glucose tolerance in acromegaly. Subjects and Study Design: We conducted a retrospective cross-sectional study that included 48 patients with active acromegaly. The subjects were divided into two groups by the results of 75 g OGTT: normal glucose tolerance (NGT) group (n = 19) and IGT+DM group (n = 29). Results: Systolic blood pressure (SBP) was significantly higher in the IGT+DM than in the NGT group. Homeostasis model assessment of β-cell function (HOMA-β) was significantly decreased in the IGT+DM group compared with the NGT group. Although serum GH or IGF-I levels were not different between the two groups, the IGF-I/GH ratio in the IGT+DM group was significantly lower than that in the NGT group. Conclusions: We have shown that a low serum IGF-I/GH ratio was associated with abnormal glucose tolerance in acromegaly. We propose that the IGF-I/GH ratio is a useful marker to understand the metabolic status in acromegaly.

Octreotide detrimental to glucose metabolism in acromegaly

Octreotide detrimental to glucose metabolism in acromegaly

Peripheral Glucose Metabolism in Acromegaly

The present study was designed to determine the effect of chronic GH excess on forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Nine normal subjects and 10 nondiabetic acromegalic patients (5 of them with normal glucose tolerance) were studied after an overnight fast (12-14 h) and for 3 h after the ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Decreased forearm glucose uptake was observed in the acromegalic patients compared to that in the normal subjects (380 +/- 84 vs. 709 +/- 56 mumol/100 mL forearm.3 h) with diminished nonoxidative glucose metabolism (262 +/- 81 vs. 572 +/- 53 mumol/100 mL forearm.3 h). The acromegalics with normal glucose tolerance also showed decreased forearm glucose uptake and nonoxidative glucose metabolism compared to normal subjects (271 +/- 124 vs. 709 +/- 56 and 133 +/- 110 vs. 572 +/- 53 mumol/100 mL forearm.3 h, respectively). Muscle glucose oxidation did not differ significantly in normal subjects, the entire group of acromegalic patients, and the acromegalics with normal glucose tolerance (137 +/- 18 vs. 118 +/- 22 vs. 138 +/- 34 mumol/100 mL forearm.3 h, respectively). Serum FFA levels and lipid oxidation rates were similar in the normal subjects and the acromegalic patients, and declined in a similar fashion after glucose ingestion. Insulin levels were significantly higher in acromegalic patients than in normal subjects before and after glucose loading. In conclusion, this study showed that the insulin resistance occurring in the presence of chronic GH excess is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism, which are early derangements because they are also observed in acromegalic patients with normal glucose tolerance.

Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance.

To characterize the diabetogenic effects of growth hormone, we simultaneously measured glucose turnover with 2-3H- and 6-3H-glucose in six acromegalic patients with normal fasting blood glucose and oral glucose tolerance tests. Eight healthy volunteers served as controls. All subjects were studied under both basal conditions and during glucose infusion (2 mg X kg-1 X min-1). We determined true glucose production and irreversible glucose uptake using 6-3H-glucose and glucose cycling (difference between 2-3H- and 6-3H-glucose). After an overnight fast, glucose production was higher than normal in the acromegalic patients (2.18 +/- 0.15 vs 1.85 +/- 0.03 mg X kg-1 X min-1, p less than 0.05) despite hyperinsulinaemia. The metabolic clearance rate was normal. During the glucose infusion, glucose production was not suppressed as effectively in the acromegalic patients as in controls nor was glucose uptake augmented, while metabolic clearance rate was decreased. In acromegaly, basal glucose cycling was increased (0.44 +/- 0.08 vs 0.25 +/- 0.07 mg X kg-1 X min-1, p less than 0.05). Furthermore cycling of endogenous glucose measured during glucose infusion was also augmented (0.41 +/- 0.05 vs 0.24 +/- 0.05 mg X kg-1 X min-1, p less than 0.05). Hence the increase of glucose cycling (70%) was much more pronounced than that of glucose production (17%). In conclusion, small defects in glucose metabolism in acromegaly can be detected with sensitive tracer methods. These derangements are confined to the liver under fasting conditions, but are of both hepatic and extrahepatic origin during glucose loading.