Glycemic,hormone, and appetite responses to monosaccharide ingestion in patients with type 2 diabetes

To investigate the relative effects of fructose and glucose on blood glucose, plasma insulin and incretin (glucagon-like peptide-1 [GLP-1] and gastric inhibitory peptide [GIP]) concentrations, and acute food intake, 10 (6 men, 4 women) patients with diet-controlled type 2 diabetes (diabetic) (44 to 71 years) and 10 age and body mass index (BMI)-matched (6 men, 4 women) nondiabetic, control subjects with varying degrees of glucose tolerance (nondiabetic), were studied on 3 days. In random order, they drank equienergetic preloads of glucose (75 g) (GLUC), fructose (75 g) (FRUCT) or vehicle (300 mL water with noncaloric flavoring [VEH]) 3 hours before an ad libitum buffet lunch. Mean glucose concentrations were lower after FRUCT than GLUC in both type 2 diabetics (FRUCT v GLUC: 7.5 +/- 0.3 v 10.8 +/- 0.4 mmol/L, P <.001) and nondiabetics (FRUCT v GLUC: 5.9 +/- 0.2 v 7.2 +/- 0.3 mmol/L, P <.05). Mean insulin concentrations were approximately 50% higher after FRUCT in type 2 diabetics than in nondiabetics (diabetics v nondiabetics: 23.1 +/- 0.7 v 15.1 +/- 1.3 microU/mL; P <.0001). Plasma GLP-1 concentrations after fructose were not different between type 2 diabetics and nondiabetics (P >.05). Glucose, but not FRUC, increased GIP concentrations, which were not different between type 2 diabetics and nondiabetics (P >.05). Food intake was suppressed 14% by GLUC (P <.05 v CONT) and 14% by FRUC (P <.05 v CONT), with no difference between the amount of food consumed after GLUC and FRUC treatment in either type 2 diabetics or nondiabetics (P >.05). We have confirmed that oral fructose ingestion produces a lower postprandial blood glucose response than equienergetic glucose and demonstrated that (1) fructose produces greater increases in plasma insulin concentration in type 2 diabetics than nondiabetics, not apparently due to greater plasma incretin concentrations and (2) fructose and glucose have equivalent short-term satiating efficiency in both type 2 diabetics and nondiabetics. We conclude that on the basis of improved glycemic control, but not satiating efficiency, fructose may be useful as a replacement for glucose in the diet of obese patients with type 2 diabetes.     

Enhanced food intake regulatory responses after a glucose drink in hyperinsulinemic men

OBJECTIVE: To determine the effect of hyperinsulinemia on food intake and plasma concentrations of glucose and food intake regulatory hormones in men after a glucose drink. DESIGN: Cross-sectional clinical intervention study of the effect of a glucose drink on food intake regulation. SUBJECTS: Thirty-three normoinsulinemic (NI) (body mass index (BMI)=25.3+/-0.6; age=41.4+/-2.4) and 32 hyperinsulinemic (HI) men (BMI=29.5+/-0.6; age=43.4+/-2.6). MEASUREMENTS: Food intake was measured from a pizza meal 1 h after subjects consumed either a noncaloric sweetened drink or a glucose-containing drink (75 g/300 ml) in random order on two occasions. On another occasion, blood samples were taken every 30 min for 2 h after the glucose drink. RESULTS: Fasting insulin in the HI and NI men was 65+/-3 (mean+/-s.e.m.) and 26+/-1.5 pmol/l, respectively. Food intake at the pizza meal was reduced by the glucose drink (P<0.01), but more so in HI (-9.7+/-4.1 %) than NI men (-5.4+/-3.4 %) (P=0.06). The increase in plasma insulin and cholecystokinin (CCK) after the glucose drink was greater and the plasma concentrations of leptin were higher, and ghrelin and adiponectin were lower in HI men than in NI men (P<0.05). CONCLUSION: These results support epidemiological data suggesting that hyperinsulinemia, at least in the early stages, may provide resistance to weight gain, possibly through physiological mechanisms of food intake control.     

Differential growth hormone responses to glucose and growth hormone releasing hormone in lactating dairy cows

Dairy cows in early lactation were reported to secrete growth hormone in response to declining glucose concentrations at day 5 but not day 30 post-partum, whereas GH responses to TRH were reported to be enhanced after day 30 post partum. The present study examined GH response following glucose infusion and the effect of GHRH as well as effects of SRIH on GHRH-stimulated GH release. Declining plasma glucose concentrations after glucose infusion stimulated GH release at day 5 post partum but not in nonpregnant, nonlactating cows or in cows at days 30 and 90 post partum. GHRH stimulated GH release on all days tested, but the response was highest at day 30 post partum when compared to other days. Somatostatin infusion inhibited GHRH effects on GH concentrations only at day 30 post partum and in nonpregnant, nonlactating cows. Thus, a differential response of the GH regulatory system could be demonstrated between days 5 and 30 post partum utilizing different stimuli. Evaluation of plasma glucose and free fatty acid concentrations on days 5, 10, 20, and 30 post partum revealed a progressive decrease in FFA but not glucose as lactation progressed. Decreased plasma FFA concentrations were paralleled by a decrease in basal GH, somatomedin-C and epinephrine. Thus, a decline in FFA may be responsible for the disparity between effects of GHRH and glucose on GH release between days 5 and 30 post partum.     

Hormonal responses in pubertal males to pulsatile gonadotropin releasing hormone (GnRH) administration

Twenty-two boys (9 with delayed puberty and 13 with short stature) ages 12.3 - 17.8 yr, and 10 adult males with idiopathic hypogonadotropic hypogonadism (ages 17.3 - 41.1 yr) have been studied following pulsatile, sc GnRH therapy (240 ng/kg/pulse) over 6 days. Mean pre- and post-therapy LH and FSH concentrations were estimated by 15 min blood sampling over 3-h periods immediately before and at the end of the treatment period. There were significant correlations between the mean pre- and posttreatment LH and FSH concentrations (r = 0.82, p less than 0.001 and r = 0.51, p less than 0.02, respectively) for the 2 groups of peripubertal boys when assessed together. Nine of the 10 adults with hypogonadism showed proportionately greater gonadotropin increments following pulsatile therapy when compared with the peripubertal boys. Standard bolus GnRH tests (100 micrograms iv) did not differentiate between the three groups of patients before pulsatile GnRH therapy. Bolus GnRH tests could predict the subsequent response to pulsatile therapy in the peripubertal boys only. There was no significant change in LH increments following the GnRH bolus tests in either group, after pulsatile GnRH administration (p greater than 0.1). Early response to pulsatile GnRH administration is dependent upon the maturity of the hypothalamic-pituitary-testicular axis in males with delayed puberty or short stature. Patients with hypogonadotropic hypogonadism do not show this relationship.     

Insulin and growth hormone responses to glucose loading in treated acromegalics

Summary The insulin and growth hormone responses to oral glucose load (100 g) in 23 acronaegalic patients, previously treated by external irradiation, are described. Based on current clinical findings, sixteen acromegalics were considered inactive and seven patients active. Two of the latter were treated diabetics. Thirteen healthy, non-obese subjects formed the control group. Five inactive acromegalics had blood glucose values exceeding the upper limits of normal after the glucose load. Both the inactive and active acromegalics had hyperinsulinemia in the fasting state and after glucose load. The observation of an exaggerated serum insulin response to glucose load in clinically inactive acromegalics suggested that chronically elevated levels of circulating growth hormone may have led to permanent changes in the responsiveness of the pancreatic islets to glucose stimulation. The mean fasting value of serum growth hormone was about the same in the controls and the inactive acromegalics; the latter did not show suppression in serum growth hormone levels after glucose load.Research Fellow, Medical Research Council of Canada     

Endogenous sex hormones and glucose tolerance status in postmenopausal women

CONTEXT: In postmenopausal women, endogenous estradiol (E2) and free testosterone (T) have been positively associated with glucose intolerance and type 2 diabetes. Most studies have not examined these associations in a large group of postmenopausal women. OBJECTIVE: The objective was to examine the association between endogenous sex hormones and glucose tolerance in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 1973 postmenopausal women ages 45-84 yr, not taking hormone replacement therapy, in the Multi-Ethnic Study of Atherosclerosis baseline examination. MAIN OUTCOME MEASURES: Impaired fasting glucose (IFG) and diabetes were defined based on fasting blood sugar and/or treatment for diabetes. In women with normal glucose tolerance, insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Increasing quartiles of bioavailable T and E2 and decreasing quartiles of SHBG were associated with significantly increased odds of IFG and diabetes (all P for trend<0.001). Except for the association of bioavailable T with diabetes, the other associations persisted after multivariable adjustment. Although higher dehydroepiandrostenedione (DHEA) was associated with greater odds of IFG (P for trend=0.02), it was not associated with diabetes. Of 1100 women with normal glucose tolerance, E2 and DHEA were positively associated, and SHBG was inversely associated with HOMA-IR (all P<0.001) after multivariable adjustment. Bioavailable T was associated with HOMA-IR (P<0.001), but not fasting glucose. CONCLUSION: Of postmenopausal women, endogenous bioavailable T, E2, and DHEA were positively associated and SHBG was negatively associated with insulin resistance.     

Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents

To determine whether peptide YY (PYY), ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and satiety responses to food intake are impaired in anorexia or obesity, we studied 30 female adolescents with anorexia nervosa [body mass index (BMI) 16.3 kg/m2], obesity (BMI 34.3 kg/m2), or normal weight (BMI 20.2 kg/m2). PYY, ghrelin, GIP, insulin, and glucose concentrations and four markers of satiety were measured for 240 min after a mixed meal. The area under the curve for glucose was similar in obese (OB) and normal-weight control (C) subjects but was 15% lower in anorexic (AN) subjects. The area under the curve for insulin was 47% lower in AN and 87% higher in OB subjects, compared with C subjects. After the meal, PYY increased significantly in C (+41%, P < 0.05) but not in AN or OB adolescents. Ghrelin concentrations were highest in AN subjects and lowest in the OB group, compared with C subjects and fell significantly by 25% in all three groups. GIP concentrations were lower in AN subjects throughout the test and increased in all three groups after the mixed meal. AN adolescents reported being less hungry than OB and C adolescents. There was a negative correlation between fasting ghrelin (but not PYY or GIP) and BMI and insulin (r2= 0.33) and a positive correlation between the decrease in hunger 15 min after the meal and PYY concentrations at 15 min (r2= 0.20). In conclusion, the blunted PYY response to a meal in OB adolescents suggests that PYY plays a role in the pathophysiology of obesity. Ghrelin is unlikely to play a causal role in anorexia nervosa or obesity. The lower GIP observed in AN subjects despite a similar caloric intake may appropriately prevent an excessive insulin response in these patients.     

Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre- and early pubertal obese girls

CONTEXT: Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear. OBJECTIVE: The objective of the study was to assess the degree of hyperandrogenemia across puberty in obese girls and assess overnight sex steroid changes in Tanner stage 1-3 girls. DESIGN: This was a cross-sectional analysis. SETTING: The study was conducted at general clinical research centers. SUBJECTS: Thirty normal-weight (body mass index for age < 85%) and 74 obese (body mass index for age >or= 95%) peripubertal girls. INTERVENTION: Blood samples (circa 0500-0700 h) were taken while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1-3 girls. MAIN OUTCOME MEASURES: Hormone concentrations stratified by Tanner stage were measured. RESULTS: Compared with normal-weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, whereas fasting insulin was 3-fold elevated in obese Tanner 1-3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05) but not in more mature girls. In a subgroup of normal-weight Tanner 1-3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P 相似文献   

Effect of clonidine on glucose, insulin and glucagon responses to a protein meal in type 2 diabetics

The authors investigated the effects of clonidine (alpha-2 stimulating agent) on blood glucose, insulin and glucagon levels in order to assess the alpha-adrenergic regulation of endocrine pancreatic secretion. Ten hypertensive female subjects affected with type 2 diabetes were studied; each subject was given a protein meal (boiled beef 200 g); blood samples were taken at -30, 0, 30, 60, 90 and 120 min; after this test each subject was treated for 4 days with clonidine (0.150 mg, 3 times/day per os); at the 5th day the protein meal was repeated under the same conditions except for the added administration of clonidine. Plasma glucose, insulin and glucagon were estimated. The administration of a protein meal caused a significant increase of blood glucose (peak at 60 min), insulin (peak at 90 min) and glucagon (peak at 90 min) levels; the association of clonidine caused an increase of blood glucose (single values and total areas) without changes of insulin and glucagon levels, when compared to those obtained before clonidine treatment. In conclusion, the association of clonidine to a protein meal caused impaired glucose tolerance presumably due to a direct glycogenolytic effect, occurring in the liver on account of an alpha-2 receptor stimulation, insulin and glucagon not being involved in this phenomenon.     

Pancreatic and gut hormone responses to mixed meal test in post-chronic pancreatitis diabetes mellitus

ObjectiveMore than one-third of chronic pancreatitis patients will eventually develop diabetes, recently classified as post-chronic pancreatitis diabetes mellitus (PPDM-C). This study was aimed to investigate the pancreatic and gut hormone responses to a mixed meal test in PPDM-C patients, compared with non-diabetic chronic pancreatitis (CP), and type 2 diabetes patients or healthy controls.Design and methodsSixteen patients with PPDM-C, 12 with non-diabetic CP as well as 10 with type 2 diabetes and healthy controls were recruited. All participants underwent mixed meal tests, and blood samples were collected for measurements of blood glucose, C-peptide, insulin, glucagon, pancreatic polypeptide (PP), ghrelin, peptide YY, glucagon like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). Indices of insulin sensitivity and secretion were calculated. Repeated measures analysis of variance was performed.ResultsParticipants with PPDM-C exhibited decreases in both fasting and postprandial responses of C-peptide (P < 0.001), insulin (P < 0.001), ghrelin (P < 0.001) and PYY (P = 0.006) compared to participants with type 2 diabetes and healthy controls. Patients with CP showed blunted glucagon, PP and incretin reactions, while the responses were increased in patients with PPDM-C compared to controls. The level of insulin sensitivity was higher for PPDM-C than type 2 diabetes (P < 0.01), however the indices for early/late-phase and overall insulin secretion (P < 0.01) were lower.ConclusionsPatients with PPDM-C are characterized by decreased C-peptide, insulin, ghrelin and PYY responses, and similar levels of glucagon, PP, GIP and GLP-1 compared to those with type 2 diabetes. The above findings, when confirmed in a larger population, may prove helpful to establish the diagnosis of PPDM-C, and should promote study on underlying pathophysiological mechanisms.     

DHEA, DHEA-S and cortisol responses to acute exercise in older adults in relation to exercise training status and sex

The aim of the present study was to investigate resting measures of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEA-S) and cortisol, and the response and recovery of these hormones to acute exercise, in male and female older adults of different exercise training status. Participants were 49 community-dwelling older adults (23 females) aged between 60 and 77 years who were either sedentary (n = 14), moderately active (n = 14) or endurance trained (n = 21). Participants undertook an acute bout of exercise in the form of an incremental submaximal treadmill test. The exercise lasted on average 23 min 49 s (SD = 2 min 8 s) and participants reached 76.5% (SD = 5.44) of the predicted maximal heart rate. Blood samples were collected prior to exercise, immediately, and 1 h post-exercise. DHEA levels significantly increased immediately post-exercise; however, DHEA-S levels only significantly increased in females. Cortisol significantly decreased immediately post-exercise and 1 h post-exercise compared to pre-exercise. There were no significant differences in resting hormone levels or hormonal responses to exercise between training status groups. The findings suggest that exercise can stimulate DHEA production in older adults and that hormonal responses to exercise differ between male and female older adults.     

Growth hormone (GH) responses to GH-releasing hormone during pubertal development in normal boys and girls: comparison to idiopathic short stature and GH deficiency

The normal ranges for GH responses to GH-releasing hormone (GHRH) have previously been defined for adult men and women. To determine whether the GHRH responses of normal children differ from those of adults and whether children with GH deficiency (GHD) and children who are growing below the first percentile but are otherwise normal (ISS) have GH responses comparable to those of normal children, we studied 90 normal children, 46 girls and 44 boys, with heights between the 10th and 95th percentiles for age, at different pubertal stages. Their responses were compared to those of 24 children with ISS and 32 children with GHD and to values previously measured in young adult men and women. Girls were grouped by Tanner breast stages and boys by testicular volumes. Plasma somatomedin-C, estradiol or testosterone, and bone age were measured in all children. All received a 1 microgram/kg iv bolus dose of GHRH-(1-44)NH2, and GH responses were measured during a 2-h sampling period. Incremental serum GH responses in girls did not change throughout pubertal development and were similar to those of adult women. The responses in boys at midpuberty were somewhat lower (P less than 0.05) than those in either prepubertal boys or adult men. ISS children had mean GH responses [23 +/- 4 (+/- SE) ng/ml] similar to those of normal children. GHD children had significantly lower mean GH responses (11 +/- 3.7 ng/ml) than normal prepubertal children (35 +/- 4.0 ng/ml; P less than 0.01), but the responses of 17 of the 32 GHD children overlapped with the normal range. GH responses to GHRH were not correlated with bone age, weight, height, SmC levels, or estradiol or testosterone concentrations. These results indicate that GH responses to GHRH testing are relatively constant throughout puberty and young adulthood, that ISS children respond normally to GHRH, and that the GHRH test is not a reliable discriminator between individual normal and GHD children.     

Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs

Responsiveness to antihypertensive medications was investigated cross-sectionally in 559 individuals comprising all treated hypertensive patients identified within a representative sample (n = 3,532, aged 40-70 years) of the Jewish population in Israel. A rate of dosage score (a summed ranking of dosages of all drugs taken) of two or more increased significantly with increasing levels of body mass index (BMI) from 37.5% in levels less than 23, 54.9% in levels 23.0-29.9, and 76.4% in levels of 30 or greater (p less than 0.0001). Multivariate analyses, adjusting for age, gender, arm circumference, and ethnic group, confirmed the independent effect of BMI on dosage score (p less than 0.001). At each level of dosage score, mean blood pressure levels were equivalent at all levels of BMI after adjusting for potential confounders. This indicates that achieved blood pressure level and not BMI itself was the main determinant of the higher dosing regimens prescribed at higher levels of BMI. In representative subgroups, glucose tolerance (n = 372) and hyperinsulinemia (n = 190) were determined and were found to be positively associated with a dosage score of two or more (p less than 0.05) independently of BMI. These effects could not be accounted for by poor compliance or by altered drug absorption or disposition since overnight urinary drug excretion and plasma drug concentrations 2 hours after ingestion, measured in 80 randomly selected patients from the study group, were not different across BMI categories at similar dosages.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of the effects of pegvisomant and octreotide on glucose, insulin, gastrin, cholecystokinin, and pancreatic polypeptide responses to oral glucose and a standard mixed meal

Standard medical therapy for patients with acromegaly includes somatostatin analogs. Owing to the widespread expression of somatostatin receptors, these may be associated with unwanted effects, such as altered glucose tolerance and impaired gut hormone release. Pegvisomant is a novel pegylated GH analog that competes with wild-type GH for GH-receptor binding sites but contains a position 120, amino acid substitution that prevents functional GH receptor dimerization, a known prerequisite for GH signal transduction and generation of IGF-I. We have studied the short-term effects of these two therapies (pegvisomant 20 mg/d for 7 d and octreotide 50 microg thrice daily for 7 d) on glucose tolerance and stimulated gut hormone release in six healthy male volunteers in an open-label, random-order, cross-over study. Subjects were assessed at baseline (oral glucose tolerance test and standard mixed meal) and on d 6 and 7 of each therapy with a minimum washout of 2 wk between treatments. Area under the curve and peak responses were analyzed using one-way repeated-measures ANOVA (on ranks where appropriate). Pegvisomant had no effect on glucose tolerance or stimulated gut hormone response during an oral glucose tolerance test and a standard meal. In contrast, octreotide significantly increased fasting plasma glucose, lowered fasting plasma insulin, and led to deterioration in glucose tolerance; three subjects developed impaired glucose tolerance and one diabetes mellitus by World Health Organization criteria. Octreotide significantly impaired stimulated release of cholecystokinin, gastrin, insulin, and pancreatic polypeptide. In conclusion, pegvisomant, unlike octreotide, is not associated with deterioration in glucose tolerance and impairment of stimulated gut hormone release in normal males.     

Luteinizing hormone responses to luteinizing hormone releasing hormone, and growth hormone and cortisol responses to insulin induced hypoglycaemia in functional secondary amenorrhoea.

Luteinizing hormone (LH) responses to luteinizing hormone releasing hormone (LHRH), and growth hormone (GH) and cortisol responses to insulin induced hypoglycaemia were studied in 56 women classified into 4 distinct groups of functional secondary amenorrhoea. The groups were: I, self-induced weight reduction (20 patients); II, post pill amenorrhoea (14 patients); III, anorexia nervosa (10 patients); and IV, idiopathic secondary amenorrhoea (12 patients). Only patients with no overlapping anamnestic factors were included. Group I patients had the most heavily impaired LHRH-LH responses, and the GH response to hypoglycaemia was smaller than in other groups. Cortisol responses were normal. Group II patients showed blunted LH responses and normal GH and cortisol responses. Group III patients showed normal or exaggerated LH responses in the recovery phase of anorexia nervosa, while those two patients who were in the static phase of the illness had impaired responses. GH responses varied greatly. Group IV patients had normal basal levels of LH and normal LH, GH and cortisol responses. The restoration of LH response is not solely correlated to body mass, since patients recovering from anorexia nervosa showed greater LHRH-LH responses with nutritional rehabilitation at 76% of ideal body weight than patients with self-induced weight reduction at 87% of ideal body weight. In idiopathic amenorrhoea the hypothalamic pituitary axis seems to be practically intact. The function of hypothalamic-pituitary axis may be impaired selectively in functional amenorrhoea. Corticotrophin releasing hormone function remains intact, and GH-response may be impaired or normal independently of the LH-response to LHRH. In self-induced weight reduction both functions were impaired. These tests are easily carried out with out-patients, and they give more information about the functional state of hypothalamic-pituitary axis than basal analyses of hypothalamic-pituitary axis than basal analyses of gonadotrophins and oestrogens. However, a single pathologic reading in the LH response is not specific enough to indicate to which group of amenorrhoea the patients belong, but these tests together elucidate the severity of lesion in hypothalamic pituitary axis.     

Growth hormone responses to oral glucose and intravenous thyrotropin-releasing hormone in acromegalic patients treated by slow-release lanreotide.

The aim of this study was to assess GH response to oral glucose tolerance test (OGTT) and TRH stimulation test in a group of 10 patients with active post-operative acromegaly before and after long-term slow-release (SR) lanreotide therapy (30 mg im every 10-14 days). Seven patients (2 males, 5 females, 29-71 yr), who during therapy maintained plasma GH and IGF-I concentrations under 5 microg/l and 450 microg/l, respectively, were considered as responders and studied for 24 (1 patient) to 36 months (6 patients). Three patients (1 male, 2 females, 46-61 yr) with levels of GH and IGF-I above those values were studied for 12 months. The OGTT (75 g po) and TRH test (400 microg iv) were repeated before and after 6, 12, 24 and 36 months. The GH response to OGTT was abnormal (nadir: >2 microg/l) at 6 and 12 months in poorly responsive patients. This response was normalized in all responsive patients. Nonetheless, 2 responsive patients showed abnormal GH values after OGTT once each throughout the 36-month study period. The GH response to TRH was characterized by great variability and exhibited unpredictable behavior throughout the study period both in responsive and in poorly responsive patients. Only 2 patients in the responsive group showed persistent normal GH levels (peak: < or =5 microg/l) after TRH for 3 yr. In conclusion, SR lanreotide treatment gave rise to a correct control of GH hypersecretion and to a normalization of GH response to oral glucose in 7 out of 10 patients, although it did not abolish the paradoxical reaction of GH to TRH in all responders. The effect of SR lanreotide on GH response to glucose tolerance test was not paralleled by GH response to TRH.     

Specific appetite,energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness

Background:

Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss.

Objective:

The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss.

Methods:

A 4-week fat overfeeding (2640 kJ excess) was performed to compare eight CT women (body mass index (BMI)<17.5 kg m⁻²) to eight female controls (BMI 18.5–25 kg m⁻²). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding.

Results:

After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P=0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22±0.18 kg, P=0.26 vs baseline), contrasting with controls (+0.72±0.26 kg, P=0.03 vs baseline, P=0.01 vs CTs). Resting energy expenditure increased in CTs only (P=0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (−2754±720 kJ, P=0.01).

Conclusion:

CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs.     

In vivo and in vitro responses to gonadotropin releasing hormone in the turtle, Chrysemys picta, in relation to sex and reproductive stage

In vivo and in vitro responsiveness to gonadotropin releasing hormone (GnRH) was studied in the turtle, Chrysemys picta, after manipulation of reproductive condition by temperature: Warm temperatures (28 degrees) induced testicular growth and ovarian regression compared to cold (17 degrees) treatment. Only males (and primarily from cold treatment) responded to GnRH injection (40 micrograms/100 g body wt intracardiac); correlated increases occurred in plasma LH and testosterone. Effects of GnRH (10 and 100 ng/ml) on LH and FSH secretion by hemipituitaries were studied in a superfusion system; tissues responded to between 0.1 and 1 ng/ml GnRH. Sex differences were evident in both acute and chronic effects of GnRH. Although both groups of females had significantly (sixfold) higher pituitary LH content, basal secretion rates of gonadotropins were similar, and LH and FSH secretion in males was more responsive to GnRH. Gonadotropin secretion rates by male glands showed high initial increments (approx four- to sevenfold) followed by an attenuation (especially LH) during 5 hr of GnRH superfusion. In contrast, tissues from warm-treated females showed a smaller initial response (approx twofold) followed by a progressive increase in output over time, and glands from cold-treated females did not respond to GnRH. Total LH secretion by superfused male hemiglands represented almost half the total LH recovered (secreted + stored); whereas, females secreted only 5% ("cold-treated") or 10% ("warm-treated") of total LH. Thus, the capacity of the pituitary to respond to GnRH is influenced by both sex and reproductive condition in the turtle. Secretion of both FSH and LH were similarly stimulated by GnRH, but thyrotropin (TSH) secretion was independent of GnRH.