c-peptide and Acromegaly

The aim of this study was to investigate interrelations among fasting glycaemia, serum C-peptide, insulin, growth hormone and plasma glucagon concentration in people with acromegaly. 22 patients with active acromegaly, 11 women and 11 men (group A) and 19 healthy people (group K) participated in the study. The oral glucose tolerance test was carried out in all participants. Blood glucose, serum C-peptide, growth hormone and plasma glucagon concentration was measured. 13 patients with acromegaly had normal glucose tolerance (group AT) and 9 had impaired glucose tolerance (group AN). Statistical analysis was performed using Student's test and regression analysis. The comparison of patients from group A and K showed, that serum growth hormone, C-peptide, insulin, blood glucose concentration in fasting state was higher in acromegaly. There were no differences in fasting plasma glucagon concentration between both groups. Fasting glycaemia was similar in patients AT and controls, but there were also higher fasting serum C-peptide and insulin concentrations in the AT group. Fasting blood glucose, serum C-peptide and insulin concentration was higher in AN group than in controls. There were no significant differences in the above parameters between AT and AN group. Analysis of regression showed the negative correlation of fasting serum growth hormone and blood glucose concentration in the group A and AT. However there was no correlation between other parameters and fasting glycaemia, in particular between fasting glycaemia and insulin concentration. Fasting glycaemia positively correlated with fasting serum insulin concentration in healthy men. The comparison of glycaemia and fasting concentration of some hormones in patients with acromegaly regarding their glucose tolerance, did not answer the question, which hormonal abnormality is the most specific for disturbances of carbohydrate metabolism in acromegaly. Therefore groups of patients with markedly high of hormones in fasting state concentrations were distinguished. There was no difference in fasting glycaemia in this people compared to patients with normal or moderately elevated concentrations of hormones studied.. There is higher fasting glycaemia in patients with acromegaly compared to healthy men. Among them one can see subjects with normal glucose tolerance that is accompanied with high serum C-peptide and insulin concentration. Disturbances of glucose-insulin interregulation occur in these people.

Topics: Acromegaly; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Child; Fasting; Female; Glucagon; Hormones; Human Growth Hormone; Humans; Insulin; Male; Middle Aged; Regression Analysis

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and β-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and β-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and β-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI(0,120)) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI(0,120) and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and β-cell function are improved by tumor resection in acromegalic patients.

Topics: Acromegaly; Adult; Asian People; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Middle Aged; Prediabetic State; Republic of Korea

In order to identify the mutual interaction between GH and leptin, we studied the effect of GH on fatty Zucker rats. GH administration at a high dose (5.0 IU/kg) reduced % body fat after 7 days. The leptin mRNA level in subcutaneous fat tissue was not changed but that in epididymal fat tissue was decreased by an even lower dose of GH (1.5 IU/kg). IGF-I treatment (200 microg/kg/day) did not change the % body fat or leptin mRNA level. These observations suggest that GH directly interacts with visceral fat and reduces fat mass and leptin expression. We also measured serum leptin levels in patients. The levels in patients with acromegaly were significantly lower than those in normal subjects with the same amount of body fat, but serum IGF-I and urinary C peptide excretion rates were higher in the acromegalic. These observations also suggests that GH directly interacts with adipose tissue and reduces leptin expression. Next we investigated the direct action of leptin on GH release from the pituitary. Leptin pretreatment of pituitary cells in culture or rats in a fasted or fed condition did not change GRH induced GH secretion. As indicated also by other recent studies, leptin may increase GRH or decrease somatostatin secretion by the hypothalamus. Thus GH interacts with fat tissues and leptin may be a good marker of the interaction.

Topics: Acromegaly; Adipose Tissue; Animals; Body Composition; C-Peptide; Female; Gene Expression Regulation; Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Rats; Rats, Wistar; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

A case with diabetes mellitus associated with growth hormone (GH)-producing pituitary adenoma is described. A 56-year-old woman who had been treated for diabetes mellitus for 3 years, was admitted for the treatment of hyperglycemia. She showed a few acromegalic features and her plasma GH level was 146 +/- 16 ng/ml. After improvement of plasma glucose level by insulin injection, octreotide therapy (100 micrograms/8 hours) was started. Seven days after the initiation of octreotide therapy, the fasting plasma glucose level was almost normalized without insulin injection. After the octreotide treatment, urinary C-peptide excretion was significantly decreased and the plasma GH level became within normal range. In this case, octreotide appears to have improved the insulin sensitivity by reducing the plasma GH level.

Topics: Acromegaly; Adenoma; Antineoplastic Agents, Hormonal; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucose Intolerance; Human Growth Hormone; Humans; Hyperglycemia; Insulin Resistance; Middle Aged; Octreotide; Pituitary Neoplasms

We investigated whether pancreatic beta-cell dysfunction has a role in the pathogenesis of glucose intolerance in acromegaly by comparing plasma intact proinsulin, immunoreactive insulin, C-peptide and glucose concentrations during a 75 g oral glucose load in six patients with active acromegaly and eight healthy volunteers. Only acromegalic patients with normal glucose tolerance were studied. Glucose concentrations were similar in acromegalic patients and controls. Acromegalic patients had higher fasting insulin (P < 0.005) and fasting C-peptide (P < 0.005) concentrations than controls. Although fasting proinsulin levels were higher in acromegalic patients than controls, this did not achieve statistical significance. Integrated insulin (P < 0.05), C-peptide (P < 0.05) and proinsulin (P < 0.005) concentrations were greater in acromegalic patients than control subjects. Integrated (P < 0.05) proinsulin:insulin molar ratios were higher in acromegalic patients than controls. Fasting and integrated insulin:C-peptide molar ratios were similar in acromegalic patients and controls. These results indicate that hyperproinsulinaemia contributes to the hyperinsulinaemia which characterizes active acromegaly. The disproportionate hyperproinsulinaemia in acromegaly suggests that prolonged and excessive growth hormone secretion may result in pancreatic beta-cell dysfunction which may predispose acromegalic subjects to glucose intolerance.

Topics: Acromegaly; Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Proinsulin

Circulating growth hormone, insulin, C-peptide, and glucose levels were compared during the sleep state in adults with acromegaly and healthy control subjects. Growth hormone secretion was episodic in both groups, with the sleep-related growth hormone peak noticeably absent in the acromegalic subjects. The mean nocturnal plasma insulin concentration was greater in the acromegalics. There was no significant difference in the C-peptide between the two groups. Insulin and glucose levels did not show an early morning rise in either acromegalics or healthy subjects. The authors conclude that there is a marked difference in the circulating levels of growth hormone and insulin between the acromegalic and the healthy groups during the sleep state, and there is no sleep-related nocturnal growth hormone peak in the acromegalic subjects. The hyperinsulinism of patients with acromegaly cannot be attributed to excess secretion of insulin.

Topics: Acromegaly; Adult; Blood Glucose; Body Mass Index; C-Peptide; Circadian Rhythm; Fasting; Female; Glucose Tolerance Test; Growth Hormone; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Male; Pancreas; Pituitary Gland, Anterior; Secretory Rate; Sleep

Hypopituitarism is associated with reduced lean body mass and increased body fat, while in acromegaly the converse is true. Fasting plasma glucose is increased in acromegaly but fasting plasma insulin and C-peptide are increased in both groups. There is a positive association between fat mass and fasting serum insulin in hypopituitarism, suggesting insulin resistance. Hypoglycaemia unresponsiveness, rather than insulin sensitivity, is the feature of growth hormone deficiency. Basal metabolic rate (expressed per kg body weight) is increased in acromegaly and decreased in hypopituitarism but when expressed 'per kg lean body mass', is increased in both groups. There is a close correlation between fat mass and fasting free fatty acid and glycerol levels in obese but not normal weight patients with hypopituitarism; slim patients appear to metabolise and oxidise their fat stores more effectively than those who remain obese. Thus indirect evidence suggests that growth hormone has an important role in maintaining normal body composition and energy stores.

Topics: Acromegaly; Adipose Tissue; Adult; Basal Metabolism; Blood Glucose; Body Composition; Body Weight; C-Peptide; Female; Humans; Hypopituitarism; Insulin; Insulin-Like Growth Factor I; Male

To examine the effect of excess growth hormones on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 6 patients with acromegaly and 6 age-, sex- and weight-matched normal subjects. The levels of plasma glucose and serum insulin were determined during fasting and every 30 min up to 180 min after 75 g of oral glucose loading. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2,min-1. The acromegalic patients had significantly higher mean levels of fasting plasma glucose (p less than 0.05) and insulin (p less than 0.01). After glucose loading for 3 h, the acromegalic patients also had a higher incremental area under the curve of plasma glucose (p less than 0.05) and serum insulin (p less than 0.05). However, no significant difference in the fasting molar ratio of C-peptide/IRI was noted between these two groups. During euglycemic clamp studies, the steady-state serum insulin levels were identical between the two groups. The glucose disposal rate was lower in acromegalics than in normal subjects (p less than 0.01). The results demonstrated that glucose intolerance, hyperinsulinemia and insulin resistance are present in acromegalic patients.

Topics: Acromegaly; Adult; Blood Glucose; C-Peptide; Female; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Male; Radioimmunoassay

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.

Topics: Acromegaly; Adult; Aged; Blood Glucose; C-Peptide; Fatty Acids, Nonesterified; Glucagon; Growth Hormone; Humans; Insulin; Middle Aged; Octreotide; Pancreatic Hormones; Somatostatin

17 patients with active acromegaly (7 of them had diabetes mellitus, too), 13 patients with type I diabetes mellitus and 20 healthy controls were examined. The residual beta-cell secretion was determined by venous Tolbutamide test and the insulin sensitivity was determined by euglycemic clamp-technique. A positive correlation was found between the growth hormone level and prolactin and the size of the basic insulin secretion. In acromegaly (with or without diabetes) the sensitivity of beta-cell apparatus towards the stimulant Tolbutamide is preserved but the insulin reserves are diminished. There exists a positive correlation between the growth hormone level and the degree of insulin resistance and between the increased prolactin level and the degree of insulin resistance in acromegalic patients.

Topics: Acromegaly; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Insulin Secretion; Male; Prolactin; Time Factors; Tolbutamide

Elevated levels of growth hormone (GH) alter both the glucose tolerance and the sensitivity of peripheral tissue to insulin. We have studied the relationship between impaired glucose metabolism and its variations with different plasma levels of endogenous GH in one patient with acromegaly. To do so, we studied the decline in blood glucose concentration, as induced by iv insulin infusion, from a given hyperglycaemic level. With high levels of GH (GH = 120 micrograms/l), the slope of the straight line representing the decrease in blood glucose after insulin infusion was -0.71, the time required to achieve normoglycaemic levels, 270 min, and the corrected area under the curve representing blood glucose 26 070 units2. After 10 months' bromocriptine treatment, GH plasma concentration fell to 8 micrograms/l, at which point the slope of the straight line was -1.40, the time required to achieve normoglycaemic levels 115 min, and the area under the curve 8956 units2. There was a greater total clearance of glucose when GH levels were lower (1.90 vs 1.00 ml/min/kg), as well as greater elimination of glucose from the extracellular glucose pool (4.02 vs 1.67 mg/min/kg). In conclusion, in this patient the elevated plasma levels of endogenous GH induced insulin resistance. Once GH levels were reduced by the administration of bromocriptine, glucose metabolism improved.

Topics: Acromegaly; Adenoma, Acidophil; Bromocriptine; C-Peptide; Female; Glucagon; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Insulin Resistance; Middle Aged; Pituitary Neoplasms; Tomography, X-Ray Computed

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.

Topics: Acromegaly; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glucagon; Glucose Tolerance Test; Glucose-6-Phosphate; Glucosephosphates; Humans; Insulin Resistance; Liver; Male; Middle Aged

The glucagon-stimulated insulin and C-peptide release in patients with active acromegaly, cured acromegalic patients and healthy controls were studied. There was an elevation of the fasting insulin levels in active acromegalics and the fasting C-peptide levels in both patient groups. After i.v. injection of glucagon the insulin and C-peptide levels increased. The highest levels were recorded in active acromegalics, but cured patients also had higher levels than the control group. The insulin/C-peptide ratio was increased in active acromegalics in comparison with that found for inactive acromegalics and normal controls. In addition, the plasma half-lives (T1/2) of endogenous insulin and C-peptide were measured. It was found that the T1/2 for insulin was increased in active acromegalics only. From this study we conclude that even when the treatment of acromegaly is effective insulin and C-peptide secretion do not normalize due, probably, to increased synthesis and release upon stimulation of the pancreatic beta-cells. In active acromegaly the removal of insulin is probably also reduced.

Topics: Acromegaly; Adult; Aged; C-Peptide; Fasting; Female; Glucagon; Half-Life; Humans; Insulin; Male; Middle Aged; Stimulation, Chemical

To assess the effects of metabolic control upon beta cell function in diabetes, pro-insulin and insulin were determined following gel-filtration of plasma at two time points in each three diabetic patients, once when the metabolic state was severely deranged and again after the metabolic state had improved after therapy. Before therapy, proinsulin concentration were 30 pM (as IRI), both fasting and at 2 hours after an oral glucose load. These values did not change with treatment. Insulin concentrations were 22 pM at both time points before therapy. With treatment, plasma insulin increased 2-fold at fasting and 7-fold at 2 hours after oral glucose. These results suggest an exhaustion of the insulin pool in beta cells during severe metabolic decompensation of diabetes, a condition which may be reversed by correction of the metabolic states of the patients with proper therapy.

Topics: Acromegaly; Adult; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Proinsulin

Topics: Acromegaly; Adult; Bromocriptine; C-Peptide; Carbohydrates; Diabetes Mellitus; Drug Evaluation; Female; Glucagon; Glucose Tolerance Test; Growth Hormone; Humans; Insulin Antibodies; Male; Middle Aged; Pancreas